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Bentley, Rex Colle

Overview:

Outcome-based research on pathology of endometrial carcinoma, including prognostic significance of histologic features of endometrial carcinoma, variants of endometrial carcinoma, definitions of atypia and well-differentiated carcinoma, and collaborative studies of oncogenes and tumor suppressor genes in endometrial carcinoma.

Endometrial pathology, especially as it relates to molecular/genetic alterations in neoplasms.

Ovarian pathology, especially as it relates to molecular and genetic alterations in neoplasms.

Improving accuracy of radiographic screening for breast cancer, by careful patho-radiographic correlation and study of improved imaging techniques (especially ultrasound).

Use of electron microscopy as a diagnostic and research technique.

Objective measures of pathology resident performance.

Positions:

Professor of Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1986

M.D. — Harvard University

Grants:

Targeting the Hippo pathway in Ras-driven rhabdomyosarcoma

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
V Foundation for Cancer Research
Role
Collaborator
Start Date
November 01, 2016
End Date
October 31, 2019

The role of MST1 in non-canonical Hippo signaling in rhabdomyosarcoma

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
Alex's Lemonade Stand
Role
Collaborator
Start Date
January 15, 2015
End Date
January 14, 2018

A Novel Hippo-Notch axis controlling embryonal rhabdomyosarcoma tumorigenesis

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
V Foundation for Cancer Research
Role
Collaborator
Start Date
June 15, 2016
End Date
June 15, 2017

The Epidemiology of Ovarian Cancer in African American Women

Administered By
Duke Cancer Institute
AwardedBy
University of Virginia - Charlottesville
Role
Co Investigator
Start Date
March 01, 2015
End Date
April 30, 2017

Tissue and Data Acquisition Activity for the Study of Gynecologic Disease

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
AwardedBy
Henry M. Jackson Foundation
Role
Collaborator
Start Date
August 19, 2016
End Date
February 28, 2017

The role of MEST (mesoderm specific transcript) in rhabdomyosarcoma

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
St. Baldrick's Foundation
Role
Collaborator
Start Date
July 01, 2015
End Date
December 31, 2016

Endometrial Cancer TCGA Project

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
AwardedBy
National Institutes of Health
Role
Pathologist
Start Date
May 20, 2010
End Date
March 31, 2015

Disparities in cervical cancer precursors and deregulation of imprinted genes

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
AwardedBy
National Institutes of Health
Role
Clinical Investigator
Start Date
June 01, 2010
End Date
April 30, 2014

Molecular Modeling of Pediatric Skeletal Muscle Tumors

Administered By
Pediatrics, Hematology-Oncology
AwardedBy
National Institutes of Health
Role
Collaborator
Start Date
January 01, 2009
End Date
November 30, 2013

Tissue and Data Acquisition Activity for the Study of Gynecologic Disease

Administered By
Obstetrics and Gynecology, Gynecologic Oncology
AwardedBy
United States Army Medical Research and Materiel Command
Role
Collaborator
Start Date
November 01, 2010
End Date
May 31, 2011

Erythropoietin Receptors in Breast Cancer

Administered By
Medicine, Hematology
AwardedBy
National Institutes of Health
Role
Investigator
Start Date
March 01, 2004
End Date
February 28, 2010

Developing Biomarker-Based Prognostics in Breast Cancer

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Consultant
Start Date
July 06, 2004
End Date
June 30, 2009

Improving genomic prediction models in breast cancer.

Administered By
Surgery, Surgical Sciences
AwardedBy
National Institutes of Health
Role
Consultant
Start Date
September 02, 2004
End Date
July 31, 2007

CDC PO- IUGR Study

Administered By
Obstetrics and Gynecology
AwardedBy
Centers for Disease Control and Prevention
Role
Pathologist
Start Date
August 01, 2003
End Date
July 31, 2004

Spore In Breast Cancer

Administered By
Surgery
AwardedBy
National Institutes of Health
Role
Co-Principal Investigator
Start Date
September 30, 1995
End Date
August 31, 1998

Role Of Type-C Retroviral Antigens In Autoimmunity

Administered By
Pathology
AwardedBy
National Institutes of Health
Role
Principal Investigator
Start Date
August 01, 1989
End Date
July 31, 1993
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Publications:

A Therapeutic Antibody for Cancer, Derived from Single Human B Cells.

Some patients with cancer never develop metastasis, and their host response might provide cues for innovative treatment strategies. We previously reported an association between autoantibodies against complement factor H (CFH) and early-stage lung cancer. CFH prevents complement-mediated cytotoxicity (CDC) by inhibiting formation of cell-lytic membrane attack complexes on self-surfaces. In an effort to translate these findings into a biologic therapy for cancer, we isolated and expressed DNA sequences encoding high-affinity human CFH antibodies directly from single, sorted B cells obtained from patients with the antibody. The co-crystal structure of a CFH antibody-target complex shows a conformational change in the target relative to the native structure. This recombinant CFH antibody causes complement activation and release of anaphylatoxins, promotes CDC of tumor cell lines, and inhibits tumor growth in vivo. The isolation of anti-tumor antibodies derived from single human B cells represents an alternative paradigm in antibody drug discovery.

Authors
Bushey, RT; Moody, MA; Nicely, NL; Haynes, BF; Alam, SM; Keir, ST; Bentley, RC; Roy Choudhury, K; Gottlin, EB; Campa, MJ; Liao, H-X; Patz, EF
MLA Citation
Bushey, RT, Moody, MA, Nicely, NL, Haynes, BF, Alam, SM, Keir, ST, Bentley, RC, Roy Choudhury, K, Gottlin, EB, Campa, MJ, Liao, H-X, and Patz, EF. "A Therapeutic Antibody for Cancer, Derived from Single Human B Cells." Cell reports 15.7 (May 4, 2016): 1505-1513.
Website
http://hdl.handle.net/10161/12221
PMID
27160908
Source
epmc
Published In
Cell Reports
Volume
15
Issue
7
Publish Date
2016
Start Page
1505
End Page
1513
DOI
10.1016/j.celrep.2016.04.038

The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia.

Vascular smooth muscle cell (SMC) migration is regulated by cytoskeletal remodeling as well as by certain transient receptor potential (TRP) channels, nonselective cation channels that modulate calcium influx. Proper function of multiple subfamily C TRP (TRPC) channels requires the scaffolding protein Homer 1, which associates with the actin-binding protein Drebrin. We found that SMC Drebrin expression is upregulated in atherosclerosis and in response to injury and investigated whether Drebrin inhibits SMC activation, either through regulation of TRP channel function via Homer or through a direct effect on the actin cytoskeleton.Wild-type (WT) and congenic Dbn(-/+) mice were subjected to wire-mediated carotid endothelial denudation. Subsequent neointimal hyperplasia was 2.4±0.3-fold greater in Dbn(-/+) than in WT mice. Levels of globular actin were equivalent in Dbn(-/+) and WT SMCs, but there was a 2.4±0.5-fold decrease in filamentous actin in Dbn(-/+) SMCs compared with WT. Filamentous actin was restored to WT levels in Dbn(-/+) SMCs by adenoviral-mediated rescue expression of Drebrin. Compared with WT SMCs, Dbn(-/+) SMCs exhibited increased TRP channel activity in response to platelet-derived growth factor, increased migration assessed in Boyden chambers, and increased proliferation. Enhanced TRP channel activity and migration in Dbn(-/+) SMCs were normalized to WT levels by rescue expression of not only WT Drebrin but also a mutant Drebrin isoform that binds actin but fails to bind Homer.Drebrin reduces SMC activation through its interaction with the actin cytoskeleton but independently of its interaction with Homer scaffolds.

Authors
Stiber, JA; Wu, J-H; Zhang, L; Nepliouev, I; Zhang, Z-S; Bryson, VG; Brian, L; Bentley, RC; Gordon-Weeks, PR; Rosenberg, PB; Freedman, NJ
MLA Citation
Stiber, JA, Wu, J-H, Zhang, L, Nepliouev, I, Zhang, Z-S, Bryson, VG, Brian, L, Bentley, RC, Gordon-Weeks, PR, Rosenberg, PB, and Freedman, NJ. "The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia." Arteriosclerosis, thrombosis, and vascular biology 36.5 (May 2016): 984-993.
PMID
27013612
Source
epmc
Published In
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume
36
Issue
5
Publish Date
2016
Start Page
984
End Page
993
DOI
10.1161/atvbaha.115.306140

Secreted Frizzled-Related Protein 3 (SFRP3) Is Required for Tumorigenesis of PAX3-FOXO1-Positive Alveolar Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is a soft tissue sarcoma associated with the skeletal muscle lineage. Of the two predominant subtypes, known as embryonal (eRMS) and alveolar (aRMS), aRMS has the poorer prognosis, with a five-year survival rate of <50%. The majority of aRMS tumors express the fusion protein PAX3-FOXO1. As PAX3-FOXO1 has proven chemically intractable, this study aims to identify targetable proteins that are downstream from or cooperate with PAX3-FOXO1 to support tumorigenesis.Microarray analysis of the transcriptomes of human skeletal muscle myoblasts expressing PAX3-FOXO1 revealed alteration of several Wnt pathway gene members, including secreted frizzled related protein 3 (SFRP3), a secreted Wnt pathway inhibitor. Loss-of-function using shRNAs against SFRP3 was used to interrogate the role of SFRP3 in human aRMS cell lines in vitro and conditional murine xenograft systems in vivo. The combination of SFRP3 genetic suppression and the chemotherapeutic agent vincristine was also examined.In vitro, suppression of SFRP3 inhibited aRMS cell growth, reduced proliferation accompanied by a G1 arrest and induction of p21, and induced apoptosis. In vivo, doxycycline-inducible suppression of SFRP3 reduced aRMS tumor growth and weight by more than three-fold, in addition to increasing myogenic differentiation and β-catenin signaling. The combination of SFRP3 suppression and vincristine was more effective at reducing aRMS cell growth in vitro than either treatment alone, and ablated tumorigenesis in vivo.SFRP3 is necessary for the growth of human aRMS cells both in vitro and in vivo and is a promising new target for investigation in aRMS.

Authors
Kephart, JJG; Tiller, RGJ; Crose, LES; Slemmons, KK; Chen, P-H; Hinson, AR; Bentley, RC; Chi, J-TA; Linardic, CM
MLA Citation
Kephart, JJG, Tiller, RGJ, Crose, LES, Slemmons, KK, Chen, P-H, Hinson, AR, Bentley, RC, Chi, J-TA, and Linardic, CM. "Secreted Frizzled-Related Protein 3 (SFRP3) Is Required for Tumorigenesis of PAX3-FOXO1-Positive Alveolar Rhabdomyosarcoma." Clinical cancer research : an official journal of the American Association for Cancer Research 21.21 (November 2015): 4868-4880.
PMID
26071485
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
21
Issue
21
Publish Date
2015
Start Page
4868
End Page
4880
DOI
10.1158/1078-0432.ccr-14-1797

Evaluation of hybrid algorithm for analysis of scattered light using ex vivo nuclear morphology measurements of cervical epithelium.

We evaluate a new hybrid algorithm for determining nuclear morphology using angle-resolved low coherence interferometry (a/LCI) measurements in ex vivo cervical tissue. The algorithm combines Mie theory based and continuous wavelet transform inverse light scattering analysis. The hybrid algorithm was validated and compared to traditional Mie theory based analysis using an ex vivo tissue data set. The hybrid algorithm achieved 100% agreement with pathology in distinguishing dysplastic and non-dysplastic biopsy sites in the pilot study. Significantly, the new algorithm performed over four times faster than traditional Mie theory based analysis.

Authors
Ho, D; Drake, TK; Bentley, RC; Valea, FA; Wax, A
MLA Citation
Ho, D, Drake, TK, Bentley, RC, Valea, FA, and Wax, A. "Evaluation of hybrid algorithm for analysis of scattered light using ex vivo nuclear morphology measurements of cervical epithelium." Biomedical optics express 6.8 (August 2015): 2755-2765.
PMID
26309741
Source
epmc
Published In
Biomedical Optics Express
Volume
6
Issue
8
Publish Date
2015
Start Page
2755
End Page
2765
DOI
10.1364/boe.6.002755

Vaginal cuff thermal injury by mode of colpotomy at total laparoscopic hysterectomy: a randomized clinical trial.

STUDY OBJECTIVE: To evaluate if the use of Valleylab mode ("V mode") (Covidien, Mansfield, MA) electrothermal energy for colpotomy during total laparoscopic hysterectomy (LH) results in a smaller margin of thermal injury to the upper vagina compared with traditional cut/coagulate (cut/coag) electrothermal energy. DESIGN: Prospective randomized clinical trial (Canadian Task Force classification I). SETTING: University medical center. PATIENTS: A total of 101 subjects who underwent LH between June 2010 and August 2012. INTERVENTIONS: Subjects were randomized to colpotomy by V mode electrothermal energy or cut/coag electrothermal energy. MEASUREMENTS AND MAIN RESULTS: The primary end point was the median depth of thermal injury measured in millimeters. The secondary end points included the proportion of subjects who developed granulation tissue, induration, infection, or dehiscence at the vaginal cuff at 4 weeks, 3 months, or 6 months postoperatively. There was no significant difference in the median depth of thermal injury in the cut/coag and V mode arms (anterior margin: 0.68 mm vs 0.63 mm [p = .94], posterior margin: 0.66 mm vs 0.70 mm [p = .87], respectively). Twenty-seven percent of subjects in each arm developed at least 1 of the clinical end points at 4 weeks, 3 months, or 6 months postoperatively (granulation tissue: 6%-18% vs 8%-21%, induration: 0%-2% vs 4%-5%, infection: 0%-4% vs 0%-10%, dehiscence: 2% vs 0% in the cut/coag and V mode arms, respectively), with no difference between arms (p = 1.0). CONCLUSION: The V mode does not reduce the depth of thermal injury compared with cut/coag electrothermal energy when used for colpotomy incision during total laparoscopic hysterectomy (Clinical Trials.gov ID: NCT02080546).

Authors
Teoh, D; Lowery, WJ; Jiang, X; Ehrisman, J; Halvorson, P; Broadwater, G; Bentley, R; Secord, AA; Sobolewski, C; Berchuck, A; Havrilesky, LJ; Valea, FA; Lee, PS
MLA Citation
Teoh, D, Lowery, WJ, Jiang, X, Ehrisman, J, Halvorson, P, Broadwater, G, Bentley, R, Secord, AA, Sobolewski, C, Berchuck, A, Havrilesky, LJ, Valea, FA, and Lee, PS. "Vaginal cuff thermal injury by mode of colpotomy at total laparoscopic hysterectomy: a randomized clinical trial." February 2015.
PMID
25305572
Source
epmc
Published In
Journal of Minimally Invasive Gynecology
Volume
22
Issue
2
Publish Date
2015
Start Page
227
End Page
233
DOI
10.1016/j.jmig.2014.10.002

Role of the YAP Oncoprotein in Priming Ras-Driven Rhabdomyosarcoma.

Rhabdomyosarcoma (RMS), a cancer characterized by features of skeletal muscle histogenesis, is the most common soft tissue sarcoma of childhood and adolescence. Survival for high-risk groups is less than 30% at 5 years. RMS also occurs during adulthood, with a lower incidence but higher mortality. Recently, mutational profiling has revealed a correlation between activating Ras mutations in the embryonal (eRMS) and pleomorphic (pRMS) histologic variants of RMS, and a poorer outcome for those patients. Independently, the YAP transcriptional coactivator, an oncoprotein kept in check by the Hippo tumor suppressor pathway, is upregulated in eRMS. Here we show that YAP promotes cell proliferation and antagonizes apoptosis and myogenic differentiation of human RMS cells bearing oncogenic Ras mutations in cell culture studies in vitro and in murine xenografts in vivo. Pharmacologic inhibition of YAP by the benzoporphyrin derivative verteporfin decreased cell proliferation and tumor growth in vivo. To interrogate the temporal contribution of YAP in eRMS tumorigenesis, we used a primary human cell-based genetic model of Ras-driven RMS. Constitutively active YAP functioned as an early genetic lesion, permitting bypass of senescence and priming myoblasts to tolerate subsequent expression of hTERT and oncogenic Ras, which were necessary and sufficient to generate murine xenograft tumors mimicking RMS in vivo. This work provides evidence for cooperation between YAP and oncogenic Ras in RMS tumorigenesis, laying the foundation for preclinical co-targeting of these pathways.

Authors
Slemmons, KK; Crose, LES; Rudzinski, E; Bentley, RC; Linardic, CM
MLA Citation
Slemmons, KK, Crose, LES, Rudzinski, E, Bentley, RC, and Linardic, CM. "Role of the YAP Oncoprotein in Priming Ras-Driven Rhabdomyosarcoma." PloS one 10.10 (January 2015): e0140781-.
PMID
26496700
Source
epmc
Published In
PloS one
Volume
10
Issue
10
Publish Date
2015
Start Page
e0140781
DOI
10.1371/journal.pone.0140781

HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA.

For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at disentangling differences in HPV distribution among AA and EA women.Five-hundred and seventy-two women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infections were detected using HPV linear array, and chi-squared tests and linear regression models were used to compare HPV genotypes across racial/ethnic groups by CIN status.Of the 572 participants, 494 (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and 88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with multiple HPV genotypes. After adjusting for race, age, parity, income, oral contraception use, and current smoking, AAs were two times less likely to harbor HPV 16/18 (OR 0.48, 95 % CI 0.21-0.94, p = 0.03) when all women were considered. This association remained unchanged when only women with CIN2/3 lesions were examined (OR 0.22, 95 % CI 0.05-0.95, p = 0.04). The most frequent high-risk HPV genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33, 35, 45, 58, and 68 were the most frequent ones detected in AAs.Our data suggest that while HPV 16/18 are the most common genotypes among EA women with CIN, AAs may harbor different genotypes.

Authors
Vidal, AC; Smith, JS; Valea, F; Bentley, R; Gradison, M; Yarnall, KSH; Ford, A; Overcash, F; Grant, K; Murphy, SK; Hoyo, C
MLA Citation
Vidal, AC, Smith, JS, Valea, F, Bentley, R, Gradison, M, Yarnall, KSH, Ford, A, Overcash, F, Grant, K, Murphy, SK, and Hoyo, C. "HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA." Cancer causes & control : CCC 25.8 (August 2014): 1055-1062.
PMID
24928693
Source
epmc
Published In
Cancer Causes & Control
Volume
25
Issue
8
Publish Date
2014
Start Page
1055
End Page
1062
DOI
10.1007/s10552-014-0406-2

Metastatic ampullary adenocarcinoma presenting as a hydrocele: a case report.

CONTEXT: Metastases from ampullary malignancies are common, but spread to the testicle and paratesticular tissue is exceedingly rare with only 2 reported cases in the literature. CASE REPORT: We report a case of a 70 year-old male with a history of ampullary adenocarcinoma status post pancreaticoduodenectomy who presented with a symptomatic right-sided hydrocele. Subsequent pathology revealed metastatic ampullary adenocarcinoma. CONCLUSIONS: Metastasis to the testicle and paratesticular tissue from ampullary malignancies is rare, but must be considered in the evaluation of scrotal masses in patients with a history of ampullary malignancy.

Authors
Lane, WO; Bentley, RC; Hurwitz, HI; Howard, LA; Polascik, TJ; Anderson, MR; Blazer, DG
MLA Citation
Lane, WO, Bentley, RC, Hurwitz, HI, Howard, LA, Polascik, TJ, Anderson, MR, and Blazer, DG. "Metastatic ampullary adenocarcinoma presenting as a hydrocele: a case report." JOP : Journal of the pancreas 15.3 (May 27, 2014): 266-268.
PMID
24865540
Source
epmc
Published In
JOP : Journal of the pancreas
Volume
15
Issue
3
Publish Date
2014
Start Page
266
End Page
268
DOI
10.6092/1590-8577/2407

Metastatic ampullary adenocarcinoma presenting as a hydrocele: a case report

CONTEXT: Metastases from ampullary malignancies are common, but spread to the testicle and paratesticular tissue is exceedingly rare with only 2 reported cases in the literature.CASE REPORT: We report a case of a 70 year-old male with a history of ampullary adenocarcinoma status post pancreaticoduodenectomy who presented with a symptomatic right-sided hydrocele. Subsequent pathology revealed metastatic ampullary adenocarcinoma.CONCLUSIONS: Metastasis to the testicle and paratesticular tissue from ampullary malignancies is rare, but must be considered in the evaluation of scrotal masses in patients with a history of ampullary malignancy.

Authors
Lane, WO; Bentley, RC; Hurwitz, HI; Howard, LA; Polascik, TJ; Anderson, MR; Blazer, DG
MLA Citation
Lane, WO, Bentley, RC, Hurwitz, HI, Howard, LA, Polascik, TJ, Anderson, MR, and Blazer, DG. "Metastatic ampullary adenocarcinoma presenting as a hydrocele: a case report." JOP : Journal of the pancreas 15.3 (May 1, 2014): 266-268.
Source
scopus
Published In
JOP : Journal of the pancreas
Volume
15
Issue
3
Publish Date
2014
Start Page
266
End Page
268
DOI
10.6092/1590-8577/2407

Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: a single institution study of 458 patients.

The aim of this study is to determine whether a minimally invasive approach to hysterectomy is associated with an increased rate of lymph vascular space invasion (LVSI) and/or malignant pelvic peritoneal cytology in endometrial cancer.We performed a single institution analysis of 458 women with endometrial cancer who underwent either total abdominal hysterectomy (TAH) or minimally invasive hysterectomy (MIH) with use of a disposable uterine manipulator. All patients had endometrial cancer diagnosed by endometrial biopsy at a single academic institution between 2002 and 2012. Exclusion criteria were pre-operative D&C and/or hysteroscopy, uterine perforation or morcellation, and conversion to laparotomy. Multivariate logistic regression models to determine if type of hysterectomy predicts either LVSI or presence of abnormal cytology were controlled for grade, stage, depth of invasion, tumor size, cervical and adnexal involvement.LVSI was identified in 39/214 (18%) MIH and 44/242 (18%) TAH (p=0.99). Pelvic washings were malignant in 14/203 (7%) MIH and 16/241 (7%) TAH (p=1.0). Washings were atypical or inconclusive in 16/203 (8%) MIH and 6/241 (2.5%) TAH (p=0.014). In multivariate analyses, type of hysterectomy was not a significant predictor of either LVSI (p=0.29) or presence of malignant washings (p=0.66), but was a predictor of atypical or inconclusive washings (p=0.03).Minimally invasive hysterectomy with use of a uterine manipulator for endometrial cancer is not associated with LVSI or malignant cytology. Algorithms that better determine the etiology and implications of inconclusive or atypical pelvic cytology are needed to inform the possible additional risk associated with a minimally invasive approach to endometrial cancer.

Authors
Zhang, C; Havrilesky, LJ; Broadwater, G; Di Santo, N; Ehrisman, JA; Lee, PS; Berchuck, A; Alvarez Secord, A; Bean, S; Bentley, RC; Valea, FA
MLA Citation
Zhang, C, Havrilesky, LJ, Broadwater, G, Di Santo, N, Ehrisman, JA, Lee, PS, Berchuck, A, Alvarez Secord, A, Bean, S, Bentley, RC, and Valea, FA. "Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: a single institution study of 458 patients." Gynecologic oncology 133.2 (May 2014): 211-215.
PMID
24582867
Source
epmc
Published In
Gynecologic Oncology
Volume
133
Issue
2
Publish Date
2014
Start Page
211
End Page
215
DOI
10.1016/j.ygyno.2014.02.025

Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: A single institution study of 458 patients

Authors
Zhang, C; Havrilesky, LJ; Broadwater, G; Di Santo, N; Ehrisman, JA; Lee, PS; Berchuck, A; Alvarez Secord, A; Bean, S; Bentley, RC; Valea, FA
MLA Citation
Zhang, C, Havrilesky, LJ, Broadwater, G, Di Santo, N, Ehrisman, JA, Lee, PS, Berchuck, A, Alvarez Secord, A, Bean, S, Bentley, RC, and Valea, FA. "Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: A single institution study of 458 patients." Gynecologic Oncology 133.2 (May 2014): 211-215.
Source
crossref
Published In
Gynecologic Oncology
Volume
133
Issue
2
Publish Date
2014
Start Page
211
End Page
215
DOI
10.1016/j.ygyno.2014.02.025

TTF-1 Is Expressed in a Subset of Esophageal Adenocarcinomas

Authors
Layne, AC; Cummings, TJ; Guy, CD; Cardona, DM; Bentley, RC; Shealy, MJ; Zhang, X; McCall, SJ
MLA Citation
Layne, AC, Cummings, TJ, Guy, CD, Cardona, DM, Bentley, RC, Shealy, MJ, Zhang, X, and McCall, SJ. "TTF-1 Is Expressed in a Subset of Esophageal Adenocarcinomas." February 2014.
Source
wos-lite
Published In
Modern Pathology
Volume
27
Publish Date
2014
Start Page
188A
End Page
188A

TTF-1 Is Expressed in a Subset of Esophageal Adenocarcinomas

Authors
Layne, AC; Cummings, TJ; Guy, CD; Cardona, DM; Bentley, RC; Shealy, MJ; Zhang, X; McCall, SJ
MLA Citation
Layne, AC, Cummings, TJ, Guy, CD, Cardona, DM, Bentley, RC, Shealy, MJ, Zhang, X, and McCall, SJ. "TTF-1 Is Expressed in a Subset of Esophageal Adenocarcinomas." February 2014.
Source
wos-lite
Published In
Laboratory Investigation
Volume
94
Publish Date
2014
Start Page
188A
End Page
188A

Bacteria Localization and Chorion Thinning among Preterm Premature Rupture of Membranes

Bacterial colonization of the fetal membranes and its role in pathogenesis of membrane rupture is poorly understood. Prior retrospective work revealed chorion layer thinning in preterm premature rupture of membranes (PPROM) subjects. Our objective was to prospectively examine fetal membrane chorion thinning and to correlate to bacterial presence in PPROM, preterm, and term subjects.

Authors
Murtha, AP; Fortner, KB; Grotegut, CA; Ransom, CE; Bentley, RC; Feng, L; Lan, L; Heine, RP; Seed, PC
MLA Citation
Murtha, AP, Fortner, KB, Grotegut, CA, Ransom, CE, Bentley, RC, Feng, L, Lan, L, Heine, RP, and Seed, PC. "Bacteria Localization and Chorion Thinning among Preterm Premature Rupture of Membranes." PLoS One (January 8, 2014). (Academic Article)
Website
http://hdl.handle.net/10161/8299
PMID
24421883
Source
manual
Published In
PLoS One
Publish Date
2014
DOI
10.1371/journal.pone.0083338

Cystic fibrosis involving the cervix, mimicking a well-differentiated adenocarcinoma: A case report

We describe clinicopathologic and immunohistochemical features of an unusual case of cystic fibrosis manifesting in the cervix as a mass lesion, mimicking cervical adenocarcinoma. A 24-year-old nulligravida with cystic fibrosis developed heavy postcoital vaginal bleeding 4 months after starting oral contraceptives and was found to have a cervical mass. She underwent a loop electrosurgical excision of the mass, and microscopic examination revealed a florid endocervical proliferation, extending to the margins. This lesion was initially interpreted as an invasive, well-differentiated endocervical adenocarcinoma. However, on subsequent review, the lesion was found to have a low rate of proliferation, no evidence of an infiltrative growth pattern, and abundant acute inflammation. Given these findings and the absence of any residual endocervical lesion on a subsequent cold knife conization, we determined that this was a benign, likely reactive, lesion. This case, together with previous studies, suggests that women with cystic fibrosis can develop proliferative endocervical lesions and that oral contraceptives may contribute to their development. © 2013 International Society of Gynecological Pathologists.

Authors
Previs, RA; Edwards, JM; Secord, AA; Nucci, MR; Bentley, RC; Hall, AHS
MLA Citation
Previs, RA, Edwards, JM, Secord, AA, Nucci, MR, Bentley, RC, and Hall, AHS. "Cystic fibrosis involving the cervix, mimicking a well-differentiated adenocarcinoma: A case report." International Journal of Gynecological Pathology 33.1 (January 1, 2014): 100-104.
Source
scopus
Published In
International Journal of Gynecological Pathology
Volume
33
Issue
1
Publish Date
2014
Start Page
100
End Page
104
DOI
10.1097/PGP.0b013e318278b832

HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA

Purpose: For poorly understood reasons, invasive cervical cancer (ICC) incidence and mortality rates are higher in women of African descent. Oncogenic human papillomavirus (HPV) genotypes distribution may vary between European American (EA) and African-American (AA) women and may contribute to differences in ICC incidence. The current study aimed at disentangling differences in HPV distribution among AA and EA women. Methods: Five-hundred and seventy-two women were enrolled at the time of colposcopic evaluation following an abnormal liquid-based cytology screen. HPV infections were detected using HPV linear array, and chi-squared tests and linear regression models were used to compare HPV genotypes across racial/ethnic groups by CIN status. Results: Of the 572 participants, 494 (86 %) had detectable HPV; 245 (43 %) had no CIN lesion, 239 (42 %) had CIN1, and 88 (15 %) had CIN2/3. Seventy-three percent of all women were infected with multiple HPV genotypes. After adjusting for race, age, parity, income, oral contraception use, and current smoking, AAs were two times less likely to harbor HPV 16/18 (OR 0.48, 95 % CI 0.21-0.94, p = 0.03) when all women were considered. This association remained unchanged when only women with CIN2/3 lesions were examined (OR 0.22, 95 % CI 0.05-0.95, p = 0.04). The most frequent high-risk HPV genotypes detected among EAs were 16, 18, 56, 39, and 66, while HPV genotypes 33, 35, 45, 58, and 68 were the most frequent ones detected in AAs. Conclusions: Our data suggest that while HPV 16/18 are the most common genotypes among EA women with CIN, AAs may harbor different genotypes. © 2014 The Author(s).

Authors
Vidal, AC; Smith, JS; Valea, F; Bentley, R; Gradison, M; Yarnall, KSH; Ford, A; Overcash, F; Grant, K; Murphy, SK; Hoyo, C
MLA Citation
Vidal, AC, Smith, JS, Valea, F, Bentley, R, Gradison, M, Yarnall, KSH, Ford, A, Overcash, F, Grant, K, Murphy, SK, and Hoyo, C. "HPV genotypes and cervical intraepithelial neoplasia in a multiethnic cohort in the southeastern USA." Cancer Causes and Control 25.8 (January 1, 2014): 1055-1062.
Source
scopus
Published In
Cancer Causes & Control
Volume
25
Issue
8
Publish Date
2014
Start Page
1055
End Page
1062
DOI
10.1007/s10552-014-0406-2

Cystic fibrosis involving the cervix, mimicking a well-differentiated adenocarcinoma: a case report.

We describe clinicopathologic and immunohistochemical features of an unusual case of cystic fibrosis manifesting in the cervix as a mass lesion, mimicking cervical adenocarcinoma. A 24-year-old nulligravida with cystic fibrosis developed heavy postcoital vaginal bleeding 4 months after starting oral contraceptives and was found to have a cervical mass. She underwent a loop electrosurgical excision of the mass, and microscopic examination revealed a florid endocervical proliferation, extending to the margins. This lesion was initially interpreted as an invasive, well-differentiated endocervical adenocarcinoma. However, on subsequent review, the lesion was found to have a low rate of proliferation, no evidence of an infiltrative growth pattern, and abundant acute inflammation. Given these findings and the absence of any residual endocervical lesion on a subsequent cold knife conization, we determined that this was a benign, likely reactive, lesion. This case, together with previous studies, suggests that women with cystic fibrosis can develop proliferative endocervical lesions and that oral contraceptives may contribute to their development.

Authors
Previs, RA; Edwards, JM; Secord, AA; Nucci, MR; Bentley, RC; Hall, AHS
MLA Citation
Previs, RA, Edwards, JM, Secord, AA, Nucci, MR, Bentley, RC, and Hall, AHS. "Cystic fibrosis involving the cervix, mimicking a well-differentiated adenocarcinoma: a case report." International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 33.1 (January 2014): 100-104.
PMID
24300542
Source
epmc
Published In
International Journal of Gynecological Pathology
Volume
33
Issue
1
Publish Date
2014
Start Page
100
End Page
104
DOI
10.1097/pgp.0b013e318278b832

Alveolar rhabdomyosarcoma-associated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression.

Alveolar rhabdomyosarcoma (aRMS) is an aggressive sarcoma of skeletal muscle characterized by expression of the paired box 3-forkhead box protein O1 (PAX3-FOXO1) fusion oncogene. Despite its discovery nearly two decades ago, the mechanisms by which PAX3-FOXO1 drives tumor development are not well characterized. Previously, we reported that PAX3-FOXO1 supports aRMS initiation by enabling bypass of cellular senescence checkpoints. We have now found that this bypass occurs in part through PAX3-FOXO1-mediated upregulation of RASSF4, a Ras-association domain family (RASSF) member. RASSF4 expression was upregulated in PAX3-FOXO1-positive aRMS cell lines and tumors. Enhanced RASSF4 expression promoted cell cycle progression, senescence evasion, and tumorigenesis through inhibition of the Hippo pathway tumor suppressor MST1. We also found that the downstream Hippo pathway target Yes-associated protein 1 (YAP), which is ordinarily restrained by Hippo signaling, was upregulated in RMS tumors. These data suggest that Hippo pathway dysfunction promotes RMS. This work provides evidence for Hippo pathway suppression in aRMS and demonstrates a progrowth role for RASSF4. Additionally, we identify a mechanism used by PAX3-FOXO1 to inhibit MST1 signaling and promote tumorigenesis in aRMS.

Authors
Crose, LES; Galindo, KA; Kephart, JG; Chen, C; Fitamant, J; Bardeesy, N; Bentley, RC; Galindo, RL; Chi, J-TA; Linardic, CM
MLA Citation
Crose, LES, Galindo, KA, Kephart, JG, Chen, C, Fitamant, J, Bardeesy, N, Bentley, RC, Galindo, RL, Chi, J-TA, and Linardic, CM. "Alveolar rhabdomyosarcoma-associated PAX3-FOXO1 promotes tumorigenesis via Hippo pathway suppression." J Clin Invest 124.1 (January 2014): 285-296.
PMID
24334454
Source
pubmed
Published In
Journal of Clinical Investigation
Volume
124
Issue
1
Publish Date
2014
Start Page
285
End Page
296
DOI
10.1172/JCI67087

HPV Genotypes and Cervical Intraepithelial Neoplasiain a Multiethnic Cohort in the Southeastern United States

Authors
Cathrine Hoyo, SKM
MLA Citation
Cathrine Hoyo, SKM. "HPV Genotypes and Cervical Intraepithelial Neoplasiain a Multiethnic Cohort in the Southeastern United States." Journal of Vaccines & Vaccination 05.03 (2014).
Source
crossref
Published In
Journal of Vaccines and Vaccination
Volume
05
Issue
03
Publish Date
2014
DOI
10.4172/2157-7560.1000224

The chorion layer of fetal membranes is prematurely destroyed in women with preterm premature rupture of the membranes.

Preterm premature rupture of the membranes (PPROM) is an important etiology of preterm birth and source of significant neonatal morbidity. We propose that PPROM occurs in the setting of long-standing altered tissue remodeling, which creates a vulnerable environment for the fetal membranes and pregnancy. We tested the hypothesis that PPROM is the result of tissue remodeling in the fetal membranes, specifically the chorion, and this weakening of the chorion compromises the protection provided to the amnion. The purpose of this study was to quantify thickness and apoptosis in the choriodecidua of fetal membranes in patients with PPROM, preterm labor (PTL), preterm no labor (PTNL), and women with term labor (TERM). We conducted a retrospective evaluation of fetal membrane samples from 86 placentas. Immunohistochemistry was performed using a cytokeratin antibody, and mean chorion cellular thickness was compared between each clinical group. To evaluate chorion apoptosis, fetal membranes from patients with PPROM, PTL, and TERM were stained with the M30 antibody, and the degree of cellular apoptosis was determined. Statistical analysis was performed using analysis of variance with corrections for multiple comparisons. The chorion cellular layer was thinner in patients with PPROM compared to patients with PTNL and TERM (62, 140, and 169 µm, respectively, P < .0001), though not significantly different from PTL (95 µm, P > .05). The percentage of apoptotic cells within the chorion among the patients with PPROM was greater compared to PTL and TERM (24.2%, 13.1%, and 8.4%, respectively, P < .001). The chorion cellular layer is thinner and demonstrates increased apoptosis in PPROM compared to patients with PTL, PTNL, and TERM, suggesting differential remodeling between clinical phenotypes.

Authors
Canzoneri, BJ; Feng, L; Grotegut, CA; Bentley, RC; Heine, RP; Murtha, AP
MLA Citation
Canzoneri, BJ, Feng, L, Grotegut, CA, Bentley, RC, Heine, RP, and Murtha, AP. "The chorion layer of fetal membranes is prematurely destroyed in women with preterm premature rupture of the membranes." Reprod Sci 20.10 (October 2013): 1246-1254.
PMID
23536574
Source
pubmed
Published In
Reproductive Sciences
Volume
20
Issue
10
Publish Date
2013
Start Page
1246
End Page
1254
DOI
10.1177/1933719113483009

Molecular signatures of epithelial ovarian cancer: analysis of associations with tumor characteristics and epidemiologic risk factors.

BACKGROUND: Six gene expression subtypes of invasive epithelial ovarian cancer were recently defined using microarrays by Tothill and colleagues. The Cancer Genome Atlas (TCGA) project subsequently replicated these subtypes and identified a signature predictive of survival in high-grade serous (HGS) cancers. We previously validated these signatures for use in formalin-fixed paraffin-embedded tissues. The aim of the present study was to determine whether these signatures are associated with specific ovarian cancer risk factors, which would add to the evidence that they reflect the heterogeneous etiology of this disease. METHODS: We modeled signature-specific tumor characteristics and epidemiologic risk factor relationships using multiple regression and multivariate response multiple regression models in 193 patients from a case-control study of epithelial ovarian cancer. RESULTS: We observed associations between the Tothill gene expression subtype signatures and both age at diagnosis (P = 0.0008) and race (P = 0.008). Although most established epidemiologic risk factors were not associated with molecular signatures, there was an association between breast feeding (P = 0.024) and first-degree family history of breast or ovarian cancer (P = 0.034) among the 106 HGS cases. Some of the above associations were validated using gene expression microarray data from the TCGA project. Weak associations were seen with age at menarche and duration of oral contraceptive use and the TCGA survival signature. CONCLUSIONS: These data support the potential for genomic characterization to elucidate the etiologic heterogeneity of epithelial ovarian cancer. IMPACT: This study suggests that molecular signatures may augment the ability to define etiologic subtypes of epithelial ovarian cancer.

Authors
Schildkraut, JM; Iversen, ES; Akushevich, L; Whitaker, R; Bentley, RC; Berchuck, A; Marks, JR
MLA Citation
Schildkraut, JM, Iversen, ES, Akushevich, L, Whitaker, R, Bentley, RC, Berchuck, A, and Marks, JR. "Molecular signatures of epithelial ovarian cancer: analysis of associations with tumor characteristics and epidemiologic risk factors." Cancer Epidemiol Biomarkers Prev 22.10 (October 2013): 1709-1721.
PMID
23917454
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
22
Issue
10
Publish Date
2013
Start Page
1709
End Page
1721
DOI
10.1158/1055-9965.EPI-13-0192

Pseudoangiomatous stromal hyperplasia (PASH) causing massive breast enlargement: MRI findings.

Authors
Johnson, KS; Bentley, RC; Kelly Marcom, P; Baker, JA
MLA Citation
Johnson, KS, Bentley, RC, Kelly Marcom, P, and Baker, JA. "Pseudoangiomatous stromal hyperplasia (PASH) causing massive breast enlargement: MRI findings." Breast J 18.6 (November 2012): 600-601.
PMID
23110315
Source
pubmed
Published In
The Breast Journal
Volume
18
Issue
6
Publish Date
2012
Start Page
600
End Page
601
DOI
10.1111/tbj.12026

Vagina

Authors
Bean, SM; Veras, E; Bentley, RC; Robboy, SJ
MLA Citation
Bean, SM, Veras, E, Bentley, RC, and Robboy, SJ. "Vagina." Histology for Pathologists: Fourth Edition. July 16, 2012.
Source
scopus
Publish Date
2012

FGFR4 blockade exerts distinct antitumorigenic effects in human embryonal versus alveolar rhabdomyosarcoma.

PURPOSE: Rhabdomyosarcoma (RMS) is a malignancy with features of skeletal muscle, and the most common soft tissue sarcoma of childhood. Survival for high-risk groups is approximately 30% at 5 years and there are no durable therapies tailored to its genetic aberrations. During genetic modeling of the common RMS variants, embryonal RMS (eRMS) and alveolar RMS (aRMS), we noted that the receptor tyrosine kinase (RTK) fibroblast growth factor receptor 4 (FGFR4) was upregulated as an early event in aRMS. Herein, we evaluated the expression of FGFR4 in eRMS compared with aRMS, and whether FGFR4 had similar or distinct roles in their tumorigenesis. EXPERIMENTAL DESIGN: Human RMS cell lines and tumor tissue were analyzed for FGFR4 expression by immunoblot and immunohistochemistry. Genetic and pharmacologic loss-of-function of FGFR4 using virally transduced short hairpin RNA (shRNA) and the FGFR small-molecule inhibitor PD173074, respectively, were used to study the role of FGFR4 in RMS cell lines in vitro and xenografts in vivo. Expression of the antiapoptotic protein BCL2L1 was also examined. RESULTS: FGFR4 is expressed in both RMS subtypes, but protein expression is higher in aRMS. The signature aRMS gene fusion product, PAX3-FOXO1, induced FGFR4 expression in primary human myoblasts. In eRMS, FGFR4 loss-of-function reduced cell proliferation in vitro and xenograft formation in vivo. In aRMS, it diminished cell survival in vitro. In myoblasts and aRMS, FGFR4 was necessary and sufficient for expression of BCL2L1 whereas in eRMS, this induction was not observed, suggesting differential FGFR4 signaling. CONCLUSION: These studies define dichotomous roles for FGFR4 in RMS subtypes, and support further study of FGFR4 as a therapeutic target.

Authors
Crose, LES; Etheridge, KT; Chen, C; Belyea, B; Talbot, LJ; Bentley, RC; Linardic, CM
MLA Citation
Crose, LES, Etheridge, KT, Chen, C, Belyea, B, Talbot, LJ, Bentley, RC, and Linardic, CM. "FGFR4 blockade exerts distinct antitumorigenic effects in human embryonal versus alveolar rhabdomyosarcoma." Clin Cancer Res 18.14 (July 15, 2012): 3780-3790.
PMID
22648271
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
18
Issue
14
Publish Date
2012
Start Page
3780
End Page
3790
DOI
10.1158/1078-0432.CCR-10-3063

Carbonic anhydrase IX is a predictive marker of doxorubicin resistance in early-stage breast cancer independent of HER2 and TOP2A amplification.

BACKGROUND: In early-stage breast cancer, adjuvant chemotherapy is associated with significant systemic toxicity with only a modest survival benefit. Therefore, there is considerable interest in identifying predictive markers of response to therapy. Doxorubicin, one of the most common drugs used to treat breast cancer, is an anthracycline chemotherapeutic agent, a class of drugs known to be affected by hypoxia. Accordingly, we examined whether expression of the endogenous hypoxia marker carbonic anhydrase IX (CA IX) is predictive of outcome in early-stage breast cancer patients treated with doxorubicin. METHODS: We obtained 209 early-stage pre-treatment surgically-resected breast tumours from patients, who received doxorubicin in their chemotherapeutic regimen and had >10 years of follow-up. Immunohistochemistry was used to detect CA IX, and we used fluorescence in situ hybridisation to detect both human epidermal growth factor receptor (HER2) and DNA topoisomerase II-alpha (TOP2A) gene amplification. RESULTS: Carbonic anhydrase IX intensity was significantly correlated with progression-free survival (PFS) and overall survival (OS) in patients receiving 300 mg m(-2) of doxorubicin (HR=1.82 and 3.77; P=0.0014 and 0.010, respectively). There was a significant, inverse correlation between CA IX score and oestrogen receptor expression, but no significant correlations were seen with either HER2 or TOP2A ratio. CONCLUSION: We demonstrate that CA IX expression is correlated with worse PFS and OS for breast cancer patients treated with doxorubicin, independent of HER2 or TOP2A gene amplification. This study provides evidence that using CA IX to detect hypoxia in surgically-resected breast tumours may be of clinical use in choosing an appropriate chemotherapy regimen.

Authors
Betof, AS; Rabbani, ZN; Hardee, ME; Kim, SJ; Broadwater, G; Bentley, RC; Snyder, SA; Vujaskovic, Z; Oosterwijk, E; Harris, LN; Horton, JK; Dewhirst, MW; Blackwell, KL
MLA Citation
Betof, AS, Rabbani, ZN, Hardee, ME, Kim, SJ, Broadwater, G, Bentley, RC, Snyder, SA, Vujaskovic, Z, Oosterwijk, E, Harris, LN, Horton, JK, Dewhirst, MW, and Blackwell, KL. "Carbonic anhydrase IX is a predictive marker of doxorubicin resistance in early-stage breast cancer independent of HER2 and TOP2A amplification." Br J Cancer 106.5 (February 28, 2012): 916-922.
PMID
22333602
Source
pubmed
Published In
British Journal of Cancer
Volume
106
Issue
5
Publish Date
2012
Start Page
916
End Page
922
DOI
10.1038/bjc.2012.32

Malignant struma ovarii: a blinded study of 86 cases assessing which histologic features correlate with aggressive clinical behavior.

CONTEXT: Struma ovarii exhibiting malignant histology are uncommon, and an aggressive clinical course in the form of initial extraovarian spread or recurrence is even more exceptional for these tumors. OBJECTIVE: To determine whether specific histologic features have predictive value in distinguishing clinically benign from clinically malignant struma ovarii. DESIGN: Blinded analysis of 19 histologic characteristics of thyroid tumors was performed in 60 clinically benign and 26 clinically malignant struma ovarii cases, with long-term follow-up. RESULTS: Except for lack of fibrosis and macrofollicular pattern, which were more common in biologically malignant tumors (P  =  .04 and P  =  .008, respectively), and trabecular pattern, which was associated with a benign clinical course (P  =  .03), none of the other histologic features was found to be correlated with clinical behavior. The presence of the following features was similar in the biologically benign and malignant tumors: papillae, pseudo-papillae, psammoma bodies, nuclear grooves, nuclear overlap, "orphan Annie" nuclei, nuclear pseudo-inclusions, prominent nucleoli, hypercellularity, colloid scalloping, eosinophilic cytoplasm, mitoses, vascular invasion, cytologic atypia, nuclear pleomorphism, and cell size and type. Trabecular pattern and absence of fibrosis were uncommon, and there was considerable overlap of macrofollicular pattern ratio between benign and malignant cases. Thus, their practical usefulness is uncertain. CONCLUSIONS: The clinical outcome of struma ovarii cannot be predicted based on the microscopic diagnosis of the thyroid tissue or on specific histologic features. The lack of correlation between morphology and outcome in proliferative and histologically malignant struma ovarii is striking, making the behavior of these tumors particularly unpredictable.

Authors
Shaco-Levy, R; Peng, RY; Snyder, MJ; Osmond, GW; Veras, E; Bean, SM; Bentley, RC; Robboy, SJ
MLA Citation
Shaco-Levy, R, Peng, RY, Snyder, MJ, Osmond, GW, Veras, E, Bean, SM, Bentley, RC, and Robboy, SJ. "Malignant struma ovarii: a blinded study of 86 cases assessing which histologic features correlate with aggressive clinical behavior." Arch Pathol Lab Med 136.2 (February 2012): 172-178.
PMID
22288964
Source
pubmed
Published In
Archives of Pathology and Laboratory Medicine
Volume
136
Issue
2
Publish Date
2012
Start Page
172
End Page
178
DOI
10.5858/arpa.2011-0092-OA

An Analysis of the Application and Reproducibility of the NIH Consensus Guidelines for the Histologic Diagnosis of Gastrointestinal Acute Graft Versus Host Disease

Authors
Cardona, DM; Shealy, MJ; Bentley, RC; Veras, E
MLA Citation
Cardona, DM, Shealy, MJ, Bentley, RC, and Veras, E. "An Analysis of the Application and Reproducibility of the NIH Consensus Guidelines for the Histologic Diagnosis of Gastrointestinal Acute Graft Versus Host Disease." February 2012.
Source
wos-lite
Published In
Laboratory Investigation
Volume
92
Publish Date
2012
Start Page
156A
End Page
157A

An Analysis of the Application and Reproducibility of the NIH Consensus Guidelines for the Histologic Diagnosis of Gastrointestinal Acute Graft Versus Host Disease

Authors
Cardona, DM; Shealy, MJ; Bentley, RC; Veras, E
MLA Citation
Cardona, DM, Shealy, MJ, Bentley, RC, and Veras, E. "An Analysis of the Application and Reproducibility of the NIH Consensus Guidelines for the Histologic Diagnosis of Gastrointestinal Acute Graft Versus Host Disease." February 2012.
Source
wos-lite
Published In
Modern Pathology
Volume
25
Publish Date
2012
Start Page
156A
End Page
157A

Loss of ARID1A-associated protein expression is a frequent event in clear cell and endometrioid ovarian cancers.

BACKGROUND: Inactivating somatic mutations in the ARID1A gene are described in a significant fraction of clear cell and endometrioid ovarian cancers leading to loss of the corresponding protein (BAF250a). Expression of BAF250a was examined in clear cell and endometrioid cancers accrued as part of the North Carolina Ovarian Cancer Study, a population-based case-control study, to determine whether loss of expression is associated with clinical and epidemiological features. METHODS: Immunostaining for BAF250a was performed using 212 clear cell and endometrioid ovarian cancers. Associations between loss of BAF250a and clinical and epidemiological features were examined. Variables were analyzed by logistic regression. RESULTS: Loss of BAF250a expression was noted in 96 (45%) of 212 cancers: 34 (41%) of 82 clear cell cases and 62 (48%) of 130 endometrioid cases. There was no relationship between the loss of BAF250a and stage, grade, survival, or epidemiological variables. CONCLUSIONS: These data confirm that loss of the ARID1A-encoded protein BAF250a is a frequent event in the genesis of clear cell and endometrioid ovarian cancers. Loss of BAF250a was not associated with clinical or epidemiologic characteristics. One explanation for these findings is that inactivation of the chromatin remodeling pathway may be a requisite event in the development of these cancers.

Authors
Lowery, WJ; Schildkraut, JM; Akushevich, L; Bentley, R; Marks, JR; Huntsman, D; Berchuck, A
MLA Citation
Lowery, WJ, Schildkraut, JM, Akushevich, L, Bentley, R, Marks, JR, Huntsman, D, and Berchuck, A. "Loss of ARID1A-associated protein expression is a frequent event in clear cell and endometrioid ovarian cancers." Int J Gynecol Cancer 22.1 (January 2012): 9-14.
PMID
22193641
Source
pubmed
Published In
International Journal of Gynecological Cancer
Volume
22
Issue
1
Publish Date
2012
Start Page
9
End Page
14
DOI
10.1097/IGC.0b013e318231f140

Inhibition of the Notch-Hey1 axis blocks embryonal rhabdomyosarcoma tumorigenesis.

PURPOSE: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and remains refractory to combined-modality therapy in patients with high risk disease. In skeletal myogenesis, Notch signaling prevents muscle differentiation and promotes proliferation of satellite cell progeny. Given its physiologic role in myogenesis and oncogenic role in other human cancers, we hypothesized that aberrant Notch signaling may contribute to RMS tumorigenesis and present novel therapeutic opportunities. EXPERIMENTAL DESIGN: Human RMS cell lines and tumors were evaluated by immunoblot, IHC, and RT-PCR to measure Notch ligand, receptor, and target gene expression. Manipulation of Notch signaling was accomplished using genetic and pharmacologic approaches. In vitro cell growth, proliferation, and differentiation were assessed using colorimetric MTT and BrdU assays, and biochemical/morphologic changes after incubation in differentiation-promoting media, respectively. In vivo tumorigenesis was assessed using xenograft formation in SCID/beige mice. RESULTS: Notch signaling is upregulated in human RMS cell lines and tumors compared with primary skeletal muscle, especially in the embryonal (eRMS) subtype. Inhibition of Notch signaling using Notch1 RNAi or γ-secretase inhibitors reduced eRMS cell proliferation in vitro. Hey1 RNAi phenocopied Notch1 loss and permitted modest myogenic differentiation, while overexpression of an activated Notch moiety, ICN1, promoted eRMS cell proliferation and rescued pharmacologic inhibition. Finally, Notch inhibition using RNAi or γ-secretase inhibitors blocked tumorigenesis in vivo. CONCLUSIONS: Aberrant Notch-Hey1 signaling contributes to eRMS by impeding differentiation and promoting proliferation. The efficacy of Notch pathway inhibition in vivo supports the development of Notch-Hey1 axis inhibitors in the treatment of eRMS.

Authors
Belyea, BC; Naini, S; Bentley, RC; Linardic, CM
MLA Citation
Belyea, BC, Naini, S, Bentley, RC, and Linardic, CM. "Inhibition of the Notch-Hey1 axis blocks embryonal rhabdomyosarcoma tumorigenesis." Clin Cancer Res 17.23 (December 1, 2011): 7324-7336.
PMID
21948088
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
17
Issue
23
Publish Date
2011
Start Page
7324
End Page
7336
DOI
10.1158/1078-0432.CCR-11-1004

The Association of Intratumoral Germinal Centers with early-stage non-small cell lung cancer.

INTRODUCTION: Lung cancers can display immune cell infiltration although the role of an adaptive immune response in disease pathogenesis is unknown. To investigate the possibility of a functional humoral response to the tumor, we surveyed histologic sections from non-small cell lung cancer (NSCLC) tumors for germinal centers (GCs) and assessed whether there was an association between the presence of GCs and tumor stage. METHODS: Tumor sections from 91 patients with all stages of NSCLC were examined by a pathologist blinded to clinical data. GCs were identified by hematoxylin and eosin staining patterns and confirmed by immunohistochemical staining for B-cell markers, BCL-6 and CD21. The distribution of GCs within the tumor or the tumor margin was recorded. Statistical analysis was performed to evaluate the association between stage and presence of GCs. RESULTS: Thirty-five percent of all tumors evaluated contained GCs, and sections evaluated by immunohistochemistry showed positive staining for both B-cell markers. GCs were seen both within the tumor and the tumor margin, consistent with an immune response to antigen stimulation. Patients with stage I NSCLC had a higher prevalence of intratumoral GCs than patients with stages II to IV (Cochran-Armitage Trend Test p = 0.02011). There was no association of stage with GCs in the tumor margin. CONCLUSIONS: Intratumoral GCs are associated with early-stage NSCLC. Further characterization of intratumoral GCs may lead to new diagnostic and therapeutic strategies based on manipulation of the adaptive immune response.

Authors
Gottlin, EB; Bentley, RC; Campa, MJ; Pisetsky, DS; Herndon, JE; Patz, EF
MLA Citation
Gottlin, EB, Bentley, RC, Campa, MJ, Pisetsky, DS, Herndon, JE, and Patz, EF. "The Association of Intratumoral Germinal Centers with early-stage non-small cell lung cancer." J Thorac Oncol 6.10 (October 2011): 1687-1690.
PMID
21642860
Source
pubmed
Published In
Journal of Thoracic Oncology
Volume
6
Issue
10
Publish Date
2011
Start Page
1687
End Page
1690
DOI
10.1097/JTO.0b013e3182217bec

Bacteria Localization in Fetal Membranes among Subjects with Preterm Premature Rupture of Membranes

Authors
Fortner, KB; Ransom, CE; Canzoneri, BJ; Bentley, RC; Feng, L; Seed, PC; Murtha, AP
MLA Citation
Fortner, KB, Ransom, CE, Canzoneri, BJ, Bentley, RC, Feng, L, Seed, PC, and Murtha, AP. "Bacteria Localization in Fetal Membranes among Subjects with Preterm Premature Rupture of Membranes." REPRODUCTIVE SCIENCES 18.3 (March 2011): 238A-238A.
Source
wos-lite
Published In
Reproductive Sciences
Volume
18
Issue
3
Publish Date
2011
Start Page
238A
End Page
238A

Neuronal ceroid lipofuscinosis diagnosed via skin biopsy.

We aim to report that skin biopsy, a non-invasive test by neurological standards, may lead to a diagnosis. A 4-year-old male presented with a 2-year history of epilepsy and progressive developmental regression. The patient had a mildly elevated ammonia level; however, evaluation for the accumulation of excess serum amino acids and evaluation of urine for organic acids was negative. MRI revealed cerebral atrophy, and an electroencephalogram demonstrated multifocal sharp and slow waves. Due to the progressive degenerative neurologic presentation, a neurologic storage disease was favored. An axillary skin biopsy was performed, revealing eosinophilic intra-cytoplasmic inclusions within the eccrine glands. A periodic acid-Schiff stain also highlighted these inclusions. Electron microscopic studies demonstrated characteristic multiple membrane-bound inclusions within the eccrine epithelial cells, containing curvilinear inclusion material characteristic of neuronal ceroid lipofuscinosis. The clinical, histological, electron microscopic and enzymatic studies were diagnostic of late-infantile onset neuronal ceroid lipofuscinosis.

Authors
Puri, PK; Leilani Valdes, C; Angelica Selim, M; Bentley, RC
MLA Citation
Puri, PK, Leilani Valdes, C, Angelica Selim, M, and Bentley, RC. "Neuronal ceroid lipofuscinosis diagnosed via skin biopsy." J Clin Neurosci 17.12 (December 2010): 1585-1587.
PMID
20800490
Source
pubmed
Published In
Journal of Clinical Neuroscience
Volume
17
Issue
12
Publish Date
2010
Start Page
1585
End Page
1587
DOI
10.1016/j.jocn.2010.03.027

The oncotype DX recurrence score is correlated with a composite index including routinely reported pathobiologic features.

In a series of 177 breast carcinomas, we found that the Oncotype DX Recurrence Score (RS) was correlated with six pathobiologic features: estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status, and the three components of the Nottingham tumor grade. The RS also correlated with a composite index (the Breast Cancer Prognostic Score or BCPS) comprising the same six parameters. Categorical concordance was 56% and 66% using conventional and TAILORx cutoffs, respectively. Our data show that a composite prognostic index can be constructed from routinely reported breast tumor features that captures much of the information provided by the Oncotype assay at no added cost.

Authors
Geradts, J; Bean, SM; Bentley, RC; Barry, WT
MLA Citation
Geradts, J, Bean, SM, Bentley, RC, and Barry, WT. "The oncotype DX recurrence score is correlated with a composite index including routinely reported pathobiologic features." Cancer Invest 28.9 (November 2010): 969-977.
PMID
20873988
Source
pubmed
Published In
Cancer Investigation (Informa)
Volume
28
Issue
9
Publish Date
2010
Start Page
969
End Page
977
DOI
10.3109/07357907.2010.512600

Neural entrapment during uterosacral ligament suspension: an anatomic study of female cadavers.

OBJECTIVE: To describe retroperitoneal neural structures at risk during uterosacral ligament suspension and to estimate risk of neural injury based on uterosacral ligament suspension suture placement technique. METHODS: Uterosacral ligament suspension was performed in 10 unembalmed female cadavers. In each cadaver, bilateral uterosacral ligament suspension sutures were placed using different techniques, as described in the literature. Distances from the ischial spine and instances of neural entrapment were recorded. Biopsy specimens of the deepest (most dorsal) tissue that each suture traversed were immunostained with a nerve-specific (S100) antibody, and the largest nerve diameter was recorded. RESULTS: Median location of sutures relative to the ischial spine did not differ significantly by suture technique. Portions of sacral nerve roots were encircled by uterosacral ligament suspension sutures in seven cadavers. There were no instances of nerve entrapment when sutures were placed while tenting the ligament with an Allis clamp, although these sutures contained a less substantial purchase of connective tissue. In six cadavers, sacral nerves were encircled by sutures placed using a dorsal and posterior arc, regardless of the needle size. In one instance, only the larger CT-1 needle encircled sacral nerve roots. S100 immunostaining confirmed gross findings, with nerve tissue in all specimens (diameter 30-1,225 micrometers). Mean nerve diameter was significantly larger in biopsy specimens in which entrapment was noted grossly (472 micrometers compared with 108 micrometers; P<.001). CONCLUSION: Sacral nerve roots are the most vulnerable neural structures during uterosacral ligament suspension. Suture placement directly into the uterosacral ligament with a dorsal and posterior needle arc results in a higher risk of nerve entrapment compared with ventral tenting of the ligament.

Authors
Siddiqui, NY; Mitchell, TRT; Bentley, RC; Weidner, AC
MLA Citation
Siddiqui, NY, Mitchell, TRT, Bentley, RC, and Weidner, AC. "Neural entrapment during uterosacral ligament suspension: an anatomic study of female cadavers." Obstet Gynecol 116.3 (September 2010): 708-713.
PMID
20733456
Source
pubmed
Published In
Obstetrics and Gynecology
Volume
116
Issue
3
Publish Date
2010
Start Page
708
End Page
713
DOI
10.1097/AOG.0b013e3181ec658a

Primary peritoneal and ovarian cancers: an epidemiological comparative analysis.

We performed case-control analyses using data from the North Carolina Ovarian Cancer Study to determine risk factors that distinguish primary peritoneal cancer (PPC) from epithelial ovarian cancer (EOC). Our risk factor analyses were restricted to invasive serous cancers including 495 EOC cases, 62 PPC cases and 1,086 control women. Logistic regression analyses were used to calculate adjusted odds ratios and 95% confidence intervals for risk factor associations. Although many case-control associations for the invasive serous PPC cases were similar to those of the invasive serous EOC cases, some differences were observed including a twofold increase in risk of invasive serous PPC in women who were >or=35 years at last pregnancy, whereas a decreased risk was observed for invasive serous EOC risk. We could not confirm a previous report of an association between tubal ligation and PPC, a factor consistently associated with a decreased risk of EOC. The difference in the risk factor associations between invasive serous PPC and EOC cancers suggests divergent molecular development of peritoneal and ovarian cancers. A larger study to determine risk factors for invasive serous PPC is warranted.

Authors
Grant, DJ; Moorman, PG; Akushevich, L; Palmieri, RT; Bentley, RC; Schildkraut, JM
MLA Citation
Grant, DJ, Moorman, PG, Akushevich, L, Palmieri, RT, Bentley, RC, and Schildkraut, JM. "Primary peritoneal and ovarian cancers: an epidemiological comparative analysis." Cancer Causes Control 21.7 (July 2010): 991-998.
PMID
20309725
Source
pubmed
Published In
Cancer Causes & Control
Volume
21
Issue
7
Publish Date
2010
Start Page
991
End Page
998
DOI
10.1007/s10552-010-9525-6

Correlation of the Oncotype DX recurrence score with a composite index comprised of ER, PR, HER2, and breast tumor grade

Authors
Geradts, J; Bean, SM; Bentley, RC; Barry, W
MLA Citation
Geradts, J, Bean, SM, Bentley, RC, and Barry, W. "Correlation of the Oncotype DX recurrence score with a composite index comprised of ER, PR, HER2, and breast tumor grade." JOURNAL OF CLINICAL ONCOLOGY 28.15 (May 20, 2010).
Source
wos-lite
Published In
Journal of Clinical Oncology
Volume
28
Issue
15
Publish Date
2010

Gastric ulceration in a patient treated with SIR-spheres.

Authors
Jazwinski, A; Bentley, R; Teitelman, M
MLA Citation
Jazwinski, A, Bentley, R, and Teitelman, M. "Gastric ulceration in a patient treated with SIR-spheres." Clin Gastroenterol Hepatol 8.5 (May 2010): A22-.
PMID
19932765
Source
pubmed
Published In
Clinical Gastroenterology and Hepatology
Volume
8
Issue
5
Publish Date
2010
Start Page
A22
DOI
10.1016/j.cgh.2009.11.006

Is surgical excision of core biopsy proven benign papillomas of the breast necessary?

RATIONALE AND OBJECTIVES: The aim of this study was to determine if core biopsy-proven benign papillomas of the breast need to be surgically excised. MATERIALS AND METHODS: Mammographic and pathologic database review from January 1994 to January 2004 revealed 178 papillary lesions diagnosed by core biopsy in 176 women (mean age, 59 years). All lesions had >or=24 months of imaging follow-up (n = 75) or surgical correlation (n = 103). Details regarding core biopsy technique, lesion appearance, pathologic results, imaging-histopathologic concordance, and follow-up imaging were recorded. Core and surgical pathologic results were correlated. RESULTS: Of the 178 papillary lesions diagnosed at core needle biopsy, 120 (67%) were initially diagnosed as benign without atypia. The core biopsy diagnoses of benignity were confirmed for all 120 lesions by either surgical excision (n = 45) or stability after >or=2 years of imaging follow-up (n = 75). Of the remaining 58 papillary lesions, 50 were found to be atypical at core needle biopsy; 15 of those 50 (29%) were upgraded to malignancies at surgical excision. Eight of the 178 lesions (5%) were initially diagnosed as malignant papillary lesions at core needle biopsy. Seven of these eight (88%) were confirmed malignant at excision. None of the surgically proven cancers was diagnosed as benign at core biopsy. CONCLUSIONS: Close imaging follow-up rather than excision of core biopsy-proven benign papillomas was adequate given careful imaging-histopathologic correlation and excision of all atypical and discordant lesions. Individual centers should evaluate their own data and tailor their practices accordingly.

Authors
Bennett, LE; Ghate, SV; Bentley, R; Baker, JA
MLA Citation
Bennett, LE, Ghate, SV, Bentley, R, and Baker, JA. "Is surgical excision of core biopsy proven benign papillomas of the breast necessary?." Acad Radiol 17.5 (May 2010): 553-557.
PMID
20223685
Source
pubmed
Published In
Academic Radiology
Volume
17
Issue
5
Publish Date
2010
Start Page
553
End Page
557
DOI
10.1016/j.acra.2010.01.001

Natural history of biologically malignant struma ovarii: analysis of 27 cases with extraovarian spread.

The natural history of 27 cases of biologically malignant struma ovarii from a series of 88 cases of histologically malignant or histologically proliferative struma ovarii is described. The extraovarian spread was evident at presentation in 17 patients. The malignant nature of the other 10 tumors became apparent only after they recurred. The tumors measured 5 to 24.5 cm and were more than 50% thyroid tissue in all but 2 cases. The microscopic diagnosis of the thyroid tissue was follicular adenoma in 17 cases (63%), papillary carcinoma in 7 (26%), unremarkable in 2 (7%), and follicular carcinoma in 1 case (4%). Generally, the clinical course was protracted, with long-term survival documented in most patients. Clinical features predictive of biologic malignancy were the presence of adhesions, peritoneal fluid (> or = 1 L), or a serosal rent in the struma ovarii (including cystectomy). In addition, pathologic factors predictive of a poorer prognosis were large size (> or = 10 cm), strumal component more than 80%, and extensive papillary carcinoma, especially with solid areas, necrosis, and > or = 5 mitoses per 10 high-power fields. Follow-up for all patients was 1.5 to 33 years (mean=13.5 yr). On last follow-up 3 patients (11%) had no evidence of disease, 9 (33%) were alive with disease, 5 (19%) died of other causes, and 10 patients (37%) died of the disease. Death from disease occurred 1.5 to 32 years after diagnosis (mean=14 yr). Recurrence was seen as early as 2 months and as late as 29 years after initial surgery (mean=7 yr). Long-term follow-up is indicated in patients with any of the above-mentioned adverse indicators.

Authors
Shaco-Levy, R; Bean, SM; Bentley, RC; Robboy, SJ
MLA Citation
Shaco-Levy, R, Bean, SM, Bentley, RC, and Robboy, SJ. "Natural history of biologically malignant struma ovarii: analysis of 27 cases with extraovarian spread." Int J Gynecol Pathol 29.3 (May 2010): 212-227.
PMID
20407319
Source
pubmed
Published In
International Journal of Gynecological Pathology
Volume
29
Issue
3
Publish Date
2010
Start Page
212
End Page
227
DOI
10.1097/PGP.0b013e3181bfb133

Association between DNA damage response and repair genes and risk of invasive serous ovarian cancer.

BACKGROUND: We analyzed the association between 53 genes related to DNA repair and p53-mediated damage response and serous ovarian cancer risk using case-control data from the North Carolina Ovarian Cancer Study (NCOCS), a population-based, case-control study. METHODS/PRINCIPAL FINDINGS: The analysis was restricted to 364 invasive serous ovarian cancer cases and 761 controls of white, non-Hispanic race. Statistical analysis was two staged: a screen using marginal Bayes factors (BFs) for 484 SNPs and a modeling stage in which we calculated multivariate adjusted posterior probabilities of association for 77 SNPs that passed the screen. These probabilities were conditional on subject age at diagnosis/interview, batch, a DNA quality metric and genotypes of other SNPs and allowed for uncertainty in the genetic parameterizations of the SNPs and number of associated SNPs. Six SNPs had Bayes factors greater than 10 in favor of an association with invasive serous ovarian cancer. These included rs5762746 (median OR(odds ratio)(per allele) = 0.66; 95% credible interval (CI) = 0.44-1.00) and rs6005835 (median OR(per allele) = 0.69; 95% CI = 0.53-0.91) in CHEK2, rs2078486 (median OR(per allele) = 1.65; 95% CI = 1.21-2.25) and rs12951053 (median OR(per allele) = 1.65; 95% CI = 1.20-2.26) in TP53, rs411697 (median OR (rare homozygote) = 0.53; 95% CI = 0.35 - 0.79) in BACH1 and rs10131 (median OR( rare homozygote) = not estimable) in LIG4. The six most highly associated SNPs are either predicted to be functionally significant or are in LD with such a variant. The variants in TP53 were confirmed to be associated in a large follow-up study. CONCLUSIONS/SIGNIFICANCE: Based on our findings, further follow-up of the DNA repair and response pathways in a larger dataset is warranted to confirm these results.

Authors
Schildkraut, JM; Iversen, ES; Wilson, MA; Clyde, MA; Moorman, PG; Palmieri, RT; Whitaker, R; Bentley, RC; Marks, JR; Berchuck, A
MLA Citation
Schildkraut, JM, Iversen, ES, Wilson, MA, Clyde, MA, Moorman, PG, Palmieri, RT, Whitaker, R, Bentley, RC, Marks, JR, and Berchuck, A. "Association between DNA damage response and repair genes and risk of invasive serous ovarian cancer. (Published online)" PLoS One 5.4 (April 8, 2010): e10061-.
Website
http://hdl.handle.net/10161/8883
PMID
20386703
Source
pubmed
Published In
PloS one
Volume
5
Issue
4
Publish Date
2010
Start Page
e10061
DOI
10.1371/journal.pone.0010061

Colonic schwannoma visualized on FDG PET/CT.

Authors
Wang, CL; Neville, AM; Wong, TZ; Hall, AH; Paulson, EK; Bentley, RC
MLA Citation
Wang, CL, Neville, AM, Wong, TZ, Hall, AH, Paulson, EK, and Bentley, RC. "Colonic schwannoma visualized on FDG PET/CT." Clinical nuclear medicine 35.3 (March 2010): 181-183.
PMID
20173452
Source
epmc
Published In
Clinical Nuclear Medicine
Volume
35
Issue
3
Publish Date
2010
Start Page
181
End Page
183
DOI
10.1097/rlu.0b013e3181cc632a

Paget disease of the vulva: a study of 56 cases.

OBJECTIVE: To resolve controversial issues regarding vulvar Paget disease through analysis of a substantial number of cases. STUDY DESIGN: The medical records and pathology slides of 56 patients with a diagnosis of vulvar Paget disease were reviewed. Possible correlation between clinical and pathological data was examined. RESULTS: Most patients were Caucasian and their mean age at diagnosis was 69 years. The average length of follow-up was 5.6 years. The most common symptom was pruritus, almost always accompanied by erythematous-white plaques. Substantial delay between appearance of symptoms and diagnosis was observed in many patients, and was significantly associated with larger lesions. Recurrence rate after surgical management was 32%, with disease involving the perineum being the only statistically significant risk factor. Patients with positive surgical margins had an increased recurrence rate, but this was not statistically significant. Intra-operative frozen section analysis of the margins as well as radical surgery as initial treatment did not reduce recurrence rate. In general, stromal invasion was not associated with worse prognosis, but the single patient who died of disease had the deepest stromal invasion. Radiation therapy given to five patients who either had multiple positive surgical margins or experienced disease recurrence and refused additional surgery resulted in complete response with no further recurrences. On the last day of follow-up 24 patients (43%) had no evidence of disease, 24 patients (43%) were dead of other causes, 5 patients (9%) were alive with disease, 2 patients (3%) were lost to follow-up, and 1 (2%) died due to vulvar Paget disease with invasive adenocarcinoma. CONCLUSIONS: Vulvar Paget disease only rarely results in a patient's death, but long term follow-up is required, as recurrences are common and can be noted many years after the initial treatment.

Authors
Shaco-Levy, R; Bean, SM; Vollmer, RT; Jewell, E; Jones, EL; Valdes, CL; Bentley, RC; Selim, MA; Robboy, SJ
MLA Citation
Shaco-Levy, R, Bean, SM, Vollmer, RT, Jewell, E, Jones, EL, Valdes, CL, Bentley, RC, Selim, MA, and Robboy, SJ. "Paget disease of the vulva: a study of 56 cases." Eur J Obstet Gynecol Reprod Biol 149.1 (March 2010): 86-91.
PMID
19969410
Source
pubmed
Published In
European Journal of Obstetrics Gynecology and Reproductive Biology
Volume
149
Issue
1
Publish Date
2010
Start Page
86
End Page
91
DOI
10.1016/j.ejogrb.2009.11.003

Paget Disease of the Vulva - A Study of 56 Cases

Authors
Shaco-Levy, R; Bean, SM; Bentley, RC; Vollmer, RT; Papalas, JA; Selim, MA; Robboy, SJ
MLA Citation
Shaco-Levy, R, Bean, SM, Bentley, RC, Vollmer, RT, Papalas, JA, Selim, MA, and Robboy, SJ. "Paget Disease of the Vulva - A Study of 56 Cases." February 2010.
Source
wos-lite
Published In
Modern Pathology
Volume
23
Publish Date
2010
Start Page
262A
End Page
262A

Paget Disease of the Vulva - A Study of 56 Cases

Authors
Shaco-Levy, R; Bean, SM; Bentley, RC; Vollmer, RT; Papalas, JA; Selim, MA; Robboy, SJ
MLA Citation
Shaco-Levy, R, Bean, SM, Bentley, RC, Vollmer, RT, Papalas, JA, Selim, MA, and Robboy, SJ. "Paget Disease of the Vulva - A Study of 56 Cases." February 2010.
Source
wos-lite
Published In
Laboratory Investigation
Volume
90
Publish Date
2010
Start Page
262A
End Page
262A

Natural History of Biologically Malignant Struma Ovarii: Analysis of 27 Cases with Extra-Ovarian Spread

Authors
Shaco-Levy, R; Bean, SM; Bentley, RC; Robboy, SJ
MLA Citation
Shaco-Levy, R, Bean, SM, Bentley, RC, and Robboy, SJ. "Natural History of Biologically Malignant Struma Ovarii: Analysis of 27 Cases with Extra-Ovarian Spread." February 2010.
Source
wos-lite
Published In
Laboratory Investigation
Volume
90
Publish Date
2010
Start Page
262A
End Page
262A

Natural History of Biologically Malignant Struma Ovarii: Analysis of 27 Cases with Extra-Ovarian Spread

Authors
Shaco-Levy, R; Bean, SM; Bentley, RC; Robboy, SJ
MLA Citation
Shaco-Levy, R, Bean, SM, Bentley, RC, and Robboy, SJ. "Natural History of Biologically Malignant Struma Ovarii: Analysis of 27 Cases with Extra-Ovarian Spread." February 2010.
Source
wos-lite
Published In
Modern Pathology
Volume
23
Publish Date
2010
Start Page
262A
End Page
262A

Paget disease of the vulva: a histologic study of 56 cases correlating pathologic features and disease course.

The Duke experience with 56 vulvar Paget disease patients was analyzed emphasizing pathologic features and controversial issues. Nearly all patients were Caucasian, and their mean age was 69 years. The average length of follow-up was 5.6 years. For each case, the following histologic features were evaluated and their association with disease course was examined: pseudo-invasion, adnexal involvement, signet-ring cells, cytologic atypia, glands formation, epidermal acantholysis, parakeratosis, hyperkeratosis, and chronic inflammation. The recurrence rate after surgical management was 32%, with epidermal acantholysis being the only statistically significant risk factor. Stromal invasion occurred in 10 patients (18%), and was not a statistically significant adverse prognostic indicator, although the single patient who died of the disease had the deepest stromal invasion. Recurrence was more common after resections with positive surgical margins, but this correlation was not statistically significant. Intraoperative frozen section analysis of the margins did not reduce recurrence rate, nor was it useful in attaining permanent free margins. The Paget cells were consistently reactive with cytokeratin-7 and carcinoembryonic antigen and unreactive with S-100 protein, HMB-45, and Mart-1. In addition, the tumor cells were usually positive for mucin stains. This profile helps distinguish vulvar Paget disease from its mimics, Pagetoid squamous cell carcinoma and malignant melanoma.

Authors
Shaco-Levy, R; Bean, SM; Vollmer, RT; Papalas, JA; Bentley, RC; Selim, MA; Robboy, SJ
MLA Citation
Shaco-Levy, R, Bean, SM, Vollmer, RT, Papalas, JA, Bentley, RC, Selim, MA, and Robboy, SJ. "Paget disease of the vulva: a histologic study of 56 cases correlating pathologic features and disease course." Int J Gynecol Pathol 29.1 (January 2010): 69-78.
PMID
19952933
Source
pubmed
Published In
International Journal of Gynecological Pathology
Volume
29
Issue
1
Publish Date
2010
Start Page
69
End Page
78
DOI
10.1097/PGP.0b013e3181b1cc5e

A safety and survival analysis of neoadjuvant bevacizumab with standard chemoradiation in a phase I/II study compared with standard chemoradiation in locally advanced rectal cancer.

INTRODUCTION: Bevacizumab is increasingly being tested with neoadjuvant regimens in patients with localized cancer, but its effects on metastasis and survival remain unknown. This study examines the long-term outcome of clinical stage II/III rectal cancer patients treated in a prospective phase II study of bevacizumab with chemoradiation and surgery. As a benchmark, we used data from an analysis of 42 patients with locally advanced rectal cancer treated with a contemporary approach of preoperative fluoropyrimidine-based radiation therapy. MATERIALS AND METHODS: Outcome analyses were performed on 32 patients treated prospectively with neoadjuvant bevacizumab, 5-fluorouracil, radiation therapy, and surgery as well as 42 patients treated with standard fluoropyrimidine-based chemoradiation. RESULTS: Overall survival, disease-free survival, and local control showed favorable trends in patients treated with bevacizumab with chemoradiation followed by surgery. Acute and postoperative toxicity appeared acceptable. CONCLUSIONS: Neoadjuvant bevacizumab with standard chemoradiation and surgery shows promising long-term efficacy and safety profiles in locally advanced rectal cancer patients.

Authors
Willett, CG; Duda, DG; Ancukiewicz, M; Shah, M; Czito, BG; Bentley, R; Poleski, M; Fujita, H; Lauwers, GY; Carroll, M; Tyler, D; Mantyh, C; Shellito, P; Chung, DC; Clark, JW; Jain, RK
MLA Citation
Willett, CG, Duda, DG, Ancukiewicz, M, Shah, M, Czito, BG, Bentley, R, Poleski, M, Fujita, H, Lauwers, GY, Carroll, M, Tyler, D, Mantyh, C, Shellito, P, Chung, DC, Clark, JW, and Jain, RK. "A safety and survival analysis of neoadjuvant bevacizumab with standard chemoradiation in a phase I/II study compared with standard chemoradiation in locally advanced rectal cancer." Oncologist 15.8 (2010): 845-851.
PMID
20667969
Source
pubmed
Published In
The oncologist
Volume
15
Issue
8
Publish Date
2010
Start Page
845
End Page
851
DOI
10.1634/theoncologist.2010-0030

Plasma soluble VEGFR-1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer.

We explored plasma and urinary concentrations of two members of the vascular endothelial growth factor (VEGF) family and their receptors as potential response and toxicity biomarkers of bevacizumab with neoadjuvant chemoradiation in patients with localized rectal cancer. The concentrations of VEGF, placental growth factor (PlGF), soluble VEGF receptor 1 (sVEGFR-1), and sVEGFR-2 were measured in plasma and urine at baseline and during treatment. Pretreatment values and changes over time were analyzed as potential biomarkers of pathological response to treatment as well as for acute toxicity in patients with locally advanced rectal cancer treated prospectively in 2002-2008 with neoadjuvant bevacizumab, 5-fluorouracil, radiation therapy, and surgery in a phase I/II trial. Of all biomarkers, pretreatment plasma sVEGFR-1-an endogenous blocker of VEGF and PlGF, and a factor linked with "vascular normalization"-was associated with both primary tumor regression and the development of adverse events after neoadjuvant bevacizumab and chemoradiation. Based on the findings in this exploratory study, we propose that plasma sVEGFR-1 should be further studied as a potential biomarker to stratify patients in future studies of bevacizumab and/or cytotoxics in the neoadjuvant setting.

Authors
Duda, DG; Willett, CG; Ancukiewicz, M; di Tomaso, E; Shah, M; Czito, BG; Bentley, R; Poleski, M; Lauwers, GY; Carroll, M; Tyler, D; Mantyh, C; Shellito, P; Clark, JW; Jain, RK
MLA Citation
Duda, DG, Willett, CG, Ancukiewicz, M, di Tomaso, E, Shah, M, Czito, BG, Bentley, R, Poleski, M, Lauwers, GY, Carroll, M, Tyler, D, Mantyh, C, Shellito, P, Clark, JW, and Jain, RK. "Plasma soluble VEGFR-1 is a potential dual biomarker of response and toxicity for bevacizumab with chemoradiation in locally advanced rectal cancer." Oncologist 15.6 (2010): 577-583.
PMID
20484123
Source
pubmed
Published In
The oncologist
Volume
15
Issue
6
Publish Date
2010
Start Page
577
End Page
583
DOI
10.1634/theoncologist.2010-0029

Novel tumor sampling strategies to enable microarray gene expression signatures in breast cancer: a study to determine feasibility and reproducibility in the context of clinical care.

Feasibility and reproducibility of microarray biomarkers in clinical settings are doubted because of reliance on fresh frozen tissue. We sought to develop and validate a paradigm of frozen tissue collection from early breast tumors to enable use of microarray in oncology practice. Frozen core needle biopsies (CNBx) were collected from 150 clinical stage I patients during image-guided diagnostic biopsy and/or surgery. Histology and tumor content from frozen cores were compared to diagnostic specimens. Twenty-eight patients had microarray analysis to examine accuracy and reproducibility of predictive gene signatures developed for estrogen receptor (ER) and HER2. One hundred twenty-seven (85%) of 150 patients had at least one frozen core containing cancer suitable for microarray analysis. Larger tumor size, ex vivo biopsy, and use of a new specimen device increased the likelihood of obtaining adequate specimens. Sufficient quality RNA was obtained from 90% of tumor cores. Microarray signatures predicting ER and HER2 expression were developed in training sets of up to 363 surgical samples and were applied to microarray data obtained from core samples collected in clinical settings. In these samples, prediction of ER and HER2 expression achieved a sensitivity/specificity of 94%/100%, and 82%/72%, respectively. Predictions were reproducible in 83-100% of paired samples. Frozen CNBx can be readily obtained from most breast cancers without interfering with pathologic evaluation in routine clinical settings. Collection of tumor tissue at diagnostic biopsy and/or at surgery from lumpectomy specimens using image guidance resulted in sufficient samples for array analysis from over 90% of patients. Sampling of breast cancer for microarray data is reproducible and feasible in clinical practice and can yield signatures predictive of multiple breast cancer phenotypes.

Authors
Tebbit, CL; Zhai, J; Untch, BR; Ellis, MJ; Dressman, HK; Bentley, RC; Baker, JA; Marcom, PK; Nevins, JR; Marks, JR; Olson, JA
MLA Citation
Tebbit, CL, Zhai, J, Untch, BR, Ellis, MJ, Dressman, HK, Bentley, RC, Baker, JA, Marcom, PK, Nevins, JR, Marks, JR, and Olson, JA. "Novel tumor sampling strategies to enable microarray gene expression signatures in breast cancer: a study to determine feasibility and reproducibility in the context of clinical care." Breast Cancer Res Treat 118.3 (December 2009): 635-643.
PMID
19224362
Source
pubmed
Published In
Breast Cancer Research and Treatment
Volume
118
Issue
3
Publish Date
2009
Start Page
635
End Page
643
DOI
10.1007/s10549-008-0301-1

Direct evidence that bevacizumab, an anti-VEGF antibody, up-regulates SDF1alpha, CXCR4, CXCL6, and neuropilin 1 in tumors from patients with rectal cancer.

Clinical studies converge on the observation that circulating cytokines are elevated in most cancer patients by anti-vascular endothelial growth factor (VEGF) therapy. However, the source of these molecules and their relevance in tumor escape remain unknown. We examined the gene expression profiles of cancer cells and tumor-associated macrophages in tumor biopsies before and 12 days after monotherapy with the anti-VEGF antibody bevacizumab in patients with rectal carcinoma. Bevacizumab up-regulated stromal cell-derived factor 1alpha (SDF1alpha), its receptor CXCR4, and CXCL6, and down-regulated PlGF, Ang1, and Ang2 in cancer cells. In addition, bevacizumab decreased Ang1 and induced neuropilin 1 (NRP1) expression in tumor-associated macrophages. Higher SDF1alpha plasma levels during bevacizumab treatment significantly associated with distant metastasis at three years. These data show that VEGF blockade up-regulates inflammatory pathways and NRP1, which should be evaluated as potential targets for improving anti-VEGF therapy.

Authors
Xu, L; Duda, DG; di Tomaso, E; Ancukiewicz, M; Chung, DC; Lauwers, GY; Samuel, R; Shellito, P; Czito, BG; Lin, P-C; Poleski, M; Bentley, R; Clark, JW; Willett, CG; Jain, RK
MLA Citation
Xu, L, Duda, DG, di Tomaso, E, Ancukiewicz, M, Chung, DC, Lauwers, GY, Samuel, R, Shellito, P, Czito, BG, Lin, P-C, Poleski, M, Bentley, R, Clark, JW, Willett, CG, and Jain, RK. "Direct evidence that bevacizumab, an anti-VEGF antibody, up-regulates SDF1alpha, CXCR4, CXCL6, and neuropilin 1 in tumors from patients with rectal cancer." Cancer Res 69.20 (October 15, 2009): 7905-7910.
PMID
19826039
Source
pubmed
Published In
Cancer Research
Volume
69
Issue
20
Publish Date
2009
Start Page
7905
End Page
7910
DOI
10.1158/0008-5472.CAN-09-2099

Malignant struma ovarii: an analysis of 88 cases, including 27 with extraovarian spread.

Struma ovarii that display extraovarian spread or later recurrence is exceedingly rare. Among 88 patients with "malignant" struma ovarii followed for prolonged periods, several features helped to predict the adverse clinical course. Adhesions (graded 2 to 4+), peritoneal fluid (> or =1 L) or ovarian serosal rent were worrisome features, occurring in 74% of 27 biologically malignant tumors but only 10% of 61 clinically benign tumors. The size of the strumal component rather than the overall size of the ovarian teratoma also had some predictive value. Tumors with a strumal component < or =6 cm recurred rarely (7%), whereas 33% of the consult and 88% of the literature cases > or =12 cm were clinically malignant. Except for a papillary pattern or poorly differentiated cancer, no microscopic feature reliably predicted the clinical outcome, including those typically associated with malignancy in primary thyroid tumors. Among the consult cases, 7% with histologic follicular adenomas and 29% with papillary carcinomas were clinically malignant. Unequivocal vascular invasion was rare, precluding assessment of its effect. Optically clear nuclei, when extensive, were useful to diagnose papillary carcinoma, but were present nevertheless in smaller numbers in both macrofollicular and microfollicular adenomas. Eight tumors confined initially to the ovary (stage 1) recurred. Papillary carcinomas recurred earlier (average 4 y) than follicular adenomatous neoplasms (average 11 y, range: 1-29 y). Overall, the survival rate for all patients was 89% at 10 years and 84% at 25 years, indicating the need for routine long-term follow-up.

Authors
Robboy, SJ; Shaco-Levy, R; Peng, RY; Snyder, MJ; Donahue, J; Bentley, RC; Bean, S; Krigman, HR; Roth, LM; Young, RH
MLA Citation
Robboy, SJ, Shaco-Levy, R, Peng, RY, Snyder, MJ, Donahue, J, Bentley, RC, Bean, S, Krigman, HR, Roth, LM, and Young, RH. "Malignant struma ovarii: an analysis of 88 cases, including 27 with extraovarian spread." Int J Gynecol Pathol 28.5 (September 2009): 405-422.
PMID
19696610
Source
pubmed
Published In
International Journal of Gynecological Pathology
Volume
28
Issue
5
Publish Date
2009
Start Page
405
End Page
422
DOI
10.1097/PGP.0b013e3181a27777

Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study.

PURPOSE: To assess the safety and efficacy of neoadjuvant bevacizumab with standard chemoradiotherapy in locally advanced rectal cancer and explore biomarkers for response. PATIENTS AND METHODS: In a phase I/II study, 32 patients received four cycles of therapy consisting of: bevacizumab infusion (5 or 10 mg/kg) on day 1 of each cycle; fluorouracil infusion (225 mg/m(2)/24 hours) during cycles 2 to 4; external-beam irradiation (50.4 Gy in 28 fractions over 5.5 weeks); and surgery 7 to 10 weeks after completion of all therapies. We measured molecular, cellular, and physiologic biomarkers before treatment, during bevacizumab monotherapy, and during and after combination therapy. RESULTS: Tumors regressed from a mass with mean size of 5 cm (range, 3 to 12 cm) to an ulcer/scar with mean size of 2.4 cm (range, 0.7 to 6.0 cm) in all 32 patients. Histologic examination revealed either no cancer or varying numbers of scattered cancer cells in a bed of fibrosis at the primary site. This treatment resulted in an actuarial 5-year local control and overall survival of 100%. Actuarial 5-year disease-free survival was 75% and five patients developed metastases postsurgery. Bevacizumab with chemoradiotherapy showed acceptable toxicity. Bevacizumab decreased tumor interstitial fluid pressure and blood flow. Baseline plasma soluble vascular endothelial growth factor receptor 1 (sVEGFR1), plasma vascular endothelial growth factor (VEGF), placental-derived growth factor (PlGF), and interleukin 6 (IL-6) during treatment, and circulating endothelial cells (CECs) after treatment showed significant correlations with outcome. CONCLUSION: Bevacizumab with chemoradiotherapy appears safe and active and yields promising survival results in locally advanced rectal cancer. Plasma VEGF, PlGF, sVEGFR1, and IL-6 and CECs should be further evaluated as candidate biomarkers of response for this regimen.

Authors
Willett, CG; Duda, DG; di Tomaso, E; Boucher, Y; Ancukiewicz, M; Sahani, DV; Lahdenranta, J; Chung, DC; Fischman, AJ; Lauwers, GY; Shellito, P; Czito, BG; Wong, TZ; Paulson, E; Poleski, M; Vujaskovic, Z; Bentley, R; Chen, HX; Clark, JW; Jain, RK
MLA Citation
Willett, CG, Duda, DG, di Tomaso, E, Boucher, Y, Ancukiewicz, M, Sahani, DV, Lahdenranta, J, Chung, DC, Fischman, AJ, Lauwers, GY, Shellito, P, Czito, BG, Wong, TZ, Paulson, E, Poleski, M, Vujaskovic, Z, Bentley, R, Chen, HX, Clark, JW, and Jain, RK. "Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study." J Clin Oncol 27.18 (June 20, 2009): 3020-3026.
PMID
19470921
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
27
Issue
18
Publish Date
2009
Start Page
3020
End Page
3026
DOI
10.1200/JCO.2008.21.1771

Quantitative physiology of the precancerous cervix in vivo through optical spectroscopy.

Cervical cancer is the second most common female cancer worldwide. The ability to quantify physiological and morphological changes in the cervix is not only useful in the diagnosis of cervical precancers but also important in aiding the design of cost-effective detection systems for use in developing countries that lack well-established screening and diagnostic programs. We assessed the capability of a diffuse reflectance spectroscopy technique to identify contrasts in optical biomarkers that vary with different grades of cervical intraepithelial neoplasia (CIN) from normal cervical tissues. The technology consists of an optical probe and an instrument (with broadband light source, dispersive element, and detector), and a Monte Carlo algorithm to extract optical biomarker contributions including total hemoglobin (Hb) concentration, Hb saturation, and reduced scattering coefficient from the measured spectra. Among 38 patients and 89 sites examined, 46 squamous normal sites, 18 CIN 1, and 15 CIN 2(+) sites were included in the analysis. Total Hb was statistically higher in CIN 2(+) (18.3 +/- 3.6 microM, mean +/- SE) compared with normal (9.58 +/- 1.91 microM) and CIN 1 (12.8 +/- 2.6 microM), whereas scattering was significantly reduced in CIN 1 (8.3 +/- 0.8 cm(-1)) and CIN 2(+) (8.6 +/- 1.0 cm(-1)) compared with normal (10.2 +/- 1.1 cm(-1)). Hemoglobin saturation was not significantly altered in CIN 2(+) compared with normal and CIN 1. The difference in total Hb is likely because of stromal angiogenesis, whereas decreased scattering can be attributed to breakdown of collagen network in the cervical stroma.

Authors
Chang, VT-C; Cartwright, PS; Bean, SM; Palmer, GM; Bentley, RC; Ramanujam, N
MLA Citation
Chang, VT-C, Cartwright, PS, Bean, SM, Palmer, GM, Bentley, RC, and Ramanujam, N. "Quantitative physiology of the precancerous cervix in vivo through optical spectroscopy." Neoplasia 11.4 (April 2009): 325-332.
PMID
19308287
Source
pubmed
Published In
Neoplasia (New York, N.Y.)
Volume
11
Issue
4
Publish Date
2009
Start Page
325
End Page
332

Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells.

The cancer stem cell hypothesis posits that malignant growth arises from a rare population of progenitor cells within a tumor that provide it with unlimited regenerative capacity. Such cells also possess increased resistance to chemotherapeutic agents. Resurgence of chemoresistant disease after primary therapy typifies epithelial ovarian cancer and may be attributable to residual cancer stem cells, or cancer-initiating cells, that survive initial treatment. As the cell surface marker CD133 identifies cancer-initiating cells in a number of other malignancies, we sought to determine the potential role of CD133+ cells in epithelial ovarian cancer. We detected CD133 on ovarian cancer cell lines, in primary cancers and on purified epithelial cells from ascitic fluid of ovarian cancer patients. We found CD133+ ovarian cancer cells generate both CD133+ and CD133- daughter cells, whereas CD133- cells divide symmetrically. CD133+ cells exhibit enhanced resistance to platinum-based therapy, drugs commonly used as first-line agents for the treatment of ovarian cancer. Sorted CD133+ ovarian cancer cells also form more aggressive tumor xenografts at a lower inoculum than their CD133- progeny. Epigenetic changes may be integral to the behavior of cancer progenitor cells and their progeny. In this regard, we found that CD133 transcription is controlled by both histone modifications and promoter methylation. Sorted CD133- ovarian cancer cells treated with DNA methyltransferase and histone deacetylase inhibitors show a synergistic increase in cell surface CD133 expression. Moreover, DNA methylation at the ovarian tissue active P2 promoter is inversely correlated with CD133 transcription. We also found that promoter methylation increases in CD133- progeny of CD133+ cells, with CD133+ cells retaining a less methylated or unmethylated state. Taken together, our results show that CD133 expression in ovarian cancer is directly regulated by epigenetic modifications and support the idea that CD133 demarcates an ovarian cancer-initiating cell population. The activity of these cells may be epigenetically detected and such cells might serve as pertinent chemotherapeutic targets for reducing disease recurrence.

Authors
Baba, T; Convery, PA; Matsumura, N; Whitaker, RS; Kondoh, E; Perry, T; Huang, Z; Bentley, RC; Mori, S; Fujii, S; Marks, JR; Berchuck, A; Murphy, SK
MLA Citation
Baba, T, Convery, PA, Matsumura, N, Whitaker, RS, Kondoh, E, Perry, T, Huang, Z, Bentley, RC, Mori, S, Fujii, S, Marks, JR, Berchuck, A, and Murphy, SK. "Epigenetic regulation of CD133 and tumorigenicity of CD133+ ovarian cancer cells." Oncogene 28.2 (January 15, 2009): 209-218.
PMID
18836486
Source
pubmed
Published In
Oncogene: Including Oncogene Reviews
Volume
28
Issue
2
Publish Date
2009
Start Page
209
End Page
218
DOI
10.1038/onc.2008.374

Micro-CT imaging of breast tumors in rodents using a liposomal, nanoparticle contrast agent.

A long circulating liposomal, nanoscale blood pool agent encapsulating traditional iodinated contrast agent (65 mg I/mL) was used for micro-computed tomography (CT) imaging of rats implanted with R3230AC mammary carcinoma. Three-dimensional vascular architecture of tumors was imaged at 100-micron isotropic resolution. The image data showed good qualitative correlation with pathologic findings. The approach holds promise for studying tumor angiogenesis and for evaluating anti-angiogenesis therapies.

Authors
Samei, E; Saunders, RS; Badea, CT; Ghaghada, KB; Hedlund, LW; Qi, Y; Yuan, H; Bentley, RC; Mukundan, S
MLA Citation
Samei, E, Saunders, RS, Badea, CT, Ghaghada, KB, Hedlund, LW, Qi, Y, Yuan, H, Bentley, RC, and Mukundan, S. "Micro-CT imaging of breast tumors in rodents using a liposomal, nanoparticle contrast agent." Int J Nanomedicine 4 (2009): 277-282.
PMID
20011244
Source
pubmed
Published In
International journal of nanomedicine
Volume
4
Publish Date
2009
Start Page
277
End Page
282

Defining the cooperative genetic changes that temporally drive alveolar rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and adolescence. Despite advances in therapy, patients with a histologic variant of RMS known as alveolar (aRMS) have a 5-year survival rate of <30%. aRMS tissues exhibit a number of genetic changes, including loss-of-function of the p53 and Rb tumor suppressor pathways, amplification of MYCN, stabilization of telomeres, and most characteristically, reciprocal translocation of loci involving the PAX and FKHR genes, generating the PAX7-FKHR or PAX3-FKHR fusion proteins. We previously showed that PAX3-FKHR expression in primary human myoblasts, cells that can give rise to RMS, cooperated with loss of p16INK4A to promote extended proliferation. To better understand the genetic events required for aRMS formation, we then stepwise converted these cells to their transformed counterpart. PAX3-FKHR, the catalytic unit of telomerase hTERT, and MycN, in cooperation with down-regulation of p16INK4A/p14ARF expression, were necessary and sufficient to convert normal human myoblasts into tumorigenic cells that gave rise to aRMS tumors. However, the order of expression of these transgenes was critical, as only those cells expressing PAX3-FKHR early could form tumors. We therefore suggest that the translocation of PAX3 to FKHR drives proliferation of myoblasts, and a selection for loss of p16INK4A/p14ARF. These early steps, coupled with MycN amplification and telomere stabilization, then drive the cells to a fully tumorigenic state.

Authors
Naini, S; Etheridge, KT; Adam, SJ; Qualman, SJ; Bentley, RC; Counter, CM; Linardic, CM
MLA Citation
Naini, S, Etheridge, KT, Adam, SJ, Qualman, SJ, Bentley, RC, Counter, CM, and Linardic, CM. "Defining the cooperative genetic changes that temporally drive alveolar rhabdomyosarcoma." Cancer Res 68.23 (December 1, 2008): 9583-9588.
PMID
19047133
Source
pubmed
Published In
Cancer Research
Volume
68
Issue
23
Publish Date
2008
Start Page
9583
End Page
9588
DOI
10.1158/0008-5472.CAN-07-6178

A clinicogenomic model to predict lymph node metastasis in breast cancer

Authors
Danko, ME; Untch, BR; Tebbit, CL; Zhai, J; Dressman, HK; Bentley, RC; Baker, J; Marks, JR; Nevins, JR; Jr, OJA
MLA Citation
Danko, ME, Untch, BR, Tebbit, CL, Zhai, J, Dressman, HK, Bentley, RC, Baker, J, Marks, JR, Nevins, JR, and Jr, OJA. "A clinicogenomic model to predict lymph node metastasis in breast cancer." September 2008.
Source
wos-lite
Published In
Journal of The American College of Surgeons
Volume
207
Issue
3
Publish Date
2008
Start Page
S45
End Page
S45
DOI
10.1016/j.jamcollsurg.2008.06.092

Desmoplastic small round cell tumor masquerading as advanced ovarian cancer.

Desmoplastic small round cell tumor (DSRCT) is a rare abdominal malignancy usually diagnosed in young adult males. Most patients have widespread disease at presentation, with an organ of origin difficult to ascertain. A 33-year-old female presented to her gynecologist with complaints of suprapubic pressure, abdominal pain, and increased abdominal girth. She had a large intraabdominal tumor on ultrasound, thought to be ovarian cancer. She underwent surgical exploration, which confirmed a malignancy, but the exact etiology was uncertain. Final pathology was consistent with DSRCT. DSRCT is a rare malignancy that can mimic other more commonly seen tumors such as lymphoma and ovarian cancer. When encountering an extensive intraabdominal malignancy of uncertain etiology, DSRCT should be in the differential diagnosis.

Authors
Bland, AE; Shah, AA; Piscitelli, JT; Bentley, RC; Secord, AA
MLA Citation
Bland, AE, Shah, AA, Piscitelli, JT, Bentley, RC, and Secord, AA. "Desmoplastic small round cell tumor masquerading as advanced ovarian cancer." Int J Gynecol Cancer 18.4 (July 2008): 847-850.
PMID
18081791
Source
pubmed
Published In
International Journal of Gynecological Cancer
Volume
18
Issue
4
Publish Date
2008
Start Page
847
End Page
850
DOI
10.1111/j.1525-1438.2007.01110.x

Hormonal risk factors for ovarian cancer in premenopausal and postmenopausal women.

Ovarian cancer is most frequently diagnosed in postmenopausal women; however, the strongest risk predictors, pregnancy and oral contraceptive use, occur in most women in their twenties and thirties. Relatively few studies have examined how reproductive risk factors vary between pre- and postmenopausal ovarian cancer. The authors used data from a population-based, case-control study of ovarian cancer (896 cases, 967 controls) conducted in North Carolina from 1999 to 2006. Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Inverse associations with ovarian cancer were observed with duration of oral contraceptive use, later age at last use, and more recent use among premenopausal women; no significant associations were found for postmenopausal women. Analyses limited to oral contraceptive users showed that duration was a more significant predictor of risk than was timing of use. Parity was inversely associated with premenopausal but not postmenopausal ovarian cancer. Later age at pregnancy was associated with reduced risk for both pre- and postmenopausal women. Analyses among parous women showed that pregnancy timing was a stronger risk predictor than number of pregnancies. Findings suggest that associations between ovarian cancer and reproductive characteristics vary by menopausal status. Additional research is needed to further elucidate risk factors for postmenopausal disease.

Authors
Moorman, PG; Calingaert, B; Palmieri, RT; Iversen, ES; Bentley, RC; Halabi, S; Berchuck, A; Schildkraut, JM
MLA Citation
Moorman, PG, Calingaert, B, Palmieri, RT, Iversen, ES, Bentley, RC, Halabi, S, Berchuck, A, and Schildkraut, JM. "Hormonal risk factors for ovarian cancer in premenopausal and postmenopausal women." Am J Epidemiol 167.9 (May 1, 2008): 1059-1069.
PMID
18303003
Source
pubmed
Published In
American Journal of Epidemiology
Volume
167
Issue
9
Publish Date
2008
Start Page
1059
End Page
1069
DOI
10.1093/aje/kwn006

Cyclin E overexpression in epithelial ovarian cancer characterizes an etiologic subgroup.

BACKGROUND: The objective of this study was to determine whether cyclin E overexpression defines an etiologically distinct subgroup of ovarian cancer. METHODS: We analyzed data from 538 epithelial ovarian cancer cases and 629 controls enrolled in a population-based case-control study. Cyclin E protein overexpression was assessed using immunohistochemistry. Case-control and case-case comparisons were done to evaluate the relationship between cyclin E overexpression and epidemiologic risk factors. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) while adjusting for potential confounders. RESULTS: Case-control comparisons showed ovarian cancers with and without cyclin E overexpression have different associations with several epidemiologic risk factors. A dose-response relationship was observed between lifetime ovulatory cycles (LOC) and ovarian cancer that overexpressed cyclin E [OR, 1.8; 95% CI, 1.1-3.0 for moderately high LOC (265-390 cycles) and OR, 2.7; 95% CI, 1.6-4.5 for high LOC (>390 cycles) compared with low LOC (<265 cycles)], but no relationship was seen with cancers that lacked overexpression. The most important components of the LOC variable contributing to the differences in the association with the cyclin E subgroups of ovarian cancer were months of oral contraceptive use and months pregnant. CONCLUSIONS: Cyclin E overexpression is associated with a high number of LOC, largely influenced by oral contraceptive use and pregnancy. This suggests that cyclin E overexpression is a molecular signature characteristic of ovarian cancer cases that may arise via a pathway that involves ovulation-induced alterations.

Authors
Schildkraut, JM; Moorman, PG; Bland, AE; Halabi, S; Calingaert, B; Whitaker, R; Lee, PS; Elkins-Williams, T; Bentley, RC; Marks, JR; Berchuck, A
MLA Citation
Schildkraut, JM, Moorman, PG, Bland, AE, Halabi, S, Calingaert, B, Whitaker, R, Lee, PS, Elkins-Williams, T, Bentley, RC, Marks, JR, and Berchuck, A. "Cyclin E overexpression in epithelial ovarian cancer characterizes an etiologic subgroup." Cancer Epidemiol Biomarkers Prev 17.3 (March 2008): 585-593.
PMID
18349276
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
17
Issue
3
Publish Date
2008
Start Page
585
End Page
593
DOI
10.1158/1055-9965.EPI-07-0596

The prognostic significance of p53 and cyclin E overexpression in ovarian cancer: A population-based study

Authors
Barnett, JC; Bland, A; Whitaker, R; Calingaert, B; Bentley, RC; Lee, PS; Moorman, PC; Schildkraut, JM; Berchuck, A
MLA Citation
Barnett, JC, Bland, A, Whitaker, R, Calingaert, B, Bentley, RC, Lee, PS, Moorman, PC, Schildkraut, JM, and Berchuck, A. "The prognostic significance of p53 and cyclin E overexpression in ovarian cancer: A population-based study." GYNECOLOGIC ONCOLOGY 108.3 (March 2008): S125-S125.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
108
Issue
3
Publish Date
2008
Start Page
S125
End Page
S125

Stem cell marker CD133 (PROMININ-1) is epigenetically regulated in ovarian cancer

Authors
Baba, T; Convery, PA; Matsumura, N; Whitaker, RS; Perry, T; Huang, Z; Mori, S; Kondoh, E; Bentley, RC; Fujii, S; Marks, JR; Berchuck, A; Murphy, SK
MLA Citation
Baba, T, Convery, PA, Matsumura, N, Whitaker, RS, Perry, T, Huang, Z, Mori, S, Kondoh, E, Bentley, RC, Fujii, S, Marks, JR, Berchuck, A, and Murphy, SK. "Stem cell marker CD133 (PROMININ-1) is epigenetically regulated in ovarian cancer." March 2008.
Source
wos-lite
Published In
Gynecologic Oncology
Volume
108
Issue
3
Publish Date
2008
Start Page
S104
End Page
S104

Elevated CAIX Expression is Associated with an Increased Risk of Distant Failure in Early-Stage Cervical Cancer.

Tumor hypoxia is associated with adverse outcome in many malignancies. The goal of this study was to determine if elevated expression of carbonic anhydrase IX (CAIX), a biomarker of hypoxia, predicts for recurrence in early-stage cervical cancer. The charts of all patients with early-stage cervical cancer, primarily FIGO IB, treated by radical hysterectomy at our institution from 1988-2001 were reviewed. Adequate pathologic specimens from patients who recurred or who had at least three years follow-up and remained disease-free were stained for CAIX. An immunohistochemical score (IHC) was generated from the extent/intensity of staining. Outcome, as measured by freedom from recurrence (FFR), distant metastases (FFDM) and local recurrence (FFLR), was analyzed as a function of age, IHC, lymph node status (LN) and histology. Forty-two relapsing patients and 76 non-relapsing patients were evaluated. In univariate analysis, +LN, though not IHC or histology, was a significant predictor of any recurrence. Both +LN and higher IHC were associated with decreased FFDM but not FFLR. Patients with both +LN and elevated IHC more frequently exhibited distant metastases as first site of failure (5-year FFDM 50%) than patients with only +LN, elevated IHC or neither feature (70, 85 and 95%, respectively, p = 0.0004). In multivariable analysis, only +LN was significantly associated with poorer FFDM (hazard ratio 4.6, p = 0.0015) though there was a strong trend with elevated CAIX expression (p = 0.069). Elevated CAIX expression is associated with more frequent distant metastases in early-stage cervical cancer, suggesting that patients with this characteristic may benefit from more aggressive treatment.

Authors
Kirkpatrick, JP; Rabbani, ZN; Bentley, RC; Hardee, ME; Karol, S; Meyer, J; Oosterwijk, E; Havrilesky, L; Secord, AA; Vujaskovic, Z; Dewhirst, MW; Jones, EL
MLA Citation
Kirkpatrick, JP, Rabbani, ZN, Bentley, RC, Hardee, ME, Karol, S, Meyer, J, Oosterwijk, E, Havrilesky, L, Secord, AA, Vujaskovic, Z, Dewhirst, MW, and Jones, EL. "Elevated CAIX Expression is Associated with an Increased Risk of Distant Failure in Early-Stage Cervical Cancer. (Published online)" Biomark Insights 3 (February 1, 2008): 45-55.
PMID
19578493
Source
pubmed
Published In
Biomark Insights
Volume
3
Publish Date
2008
Start Page
45
End Page
55

Novel approaches to Breast Tissue Banking: The Duke Breast SPORE experience

Authors
Hutchinson, CB; Dash, RC; Bentley, RC; Olson, JA; Geradts, J
MLA Citation
Hutchinson, CB, Dash, RC, Bentley, RC, Olson, JA, and Geradts, J. "Novel approaches to Breast Tissue Banking: The Duke Breast SPORE experience." January 2008.
Source
wos-lite
Published In
Modern Pathology
Volume
21
Publish Date
2008
Start Page
38A
End Page
39A

Novel approaches to breast tissue banking: The duke breast SPORE experience

Authors
Hutchinson, CB; Dash, RC; Bentley, RC; Olson, JA; Geradts, J
MLA Citation
Hutchinson, CB, Dash, RC, Bentley, RC, Olson, JA, and Geradts, J. "Novel approaches to breast tissue banking: The duke breast SPORE experience." January 2008.
Source
wos-lite
Published In
Laboratory Investigation
Volume
88
Publish Date
2008
Start Page
38A
End Page
39A

Stem cell marker CD133 (PROMININ-1) is epigenetically regulated in ovarian cancer

Authors
Baba, T; Convey, P; Matsumura, N; Whitaker, RS; Perry, T; Huang, Z; Mori, S; Kondoh, E; Bentley, RC; Fujii, S; Berchuck, A; Murphy, SK; Marks, JR
MLA Citation
Baba, T, Convey, P, Matsumura, N, Whitaker, RS, Perry, T, Huang, Z, Mori, S, Kondoh, E, Bentley, RC, Fujii, S, Berchuck, A, Murphy, SK, and Marks, JR. "Stem cell marker CD133 (PROMININ-1) is epigenetically regulated in ovarian cancer." 2008.
Source
wos-lite
Published In
Cancer biomarkers : section A of Disease markers
Volume
4
Issue
3
Publish Date
2008
Start Page
175
End Page
176

Clinical challenges and images in GI. Invasive candidal enterocolitis.

Authors
Micames, CG; Bentley, R; Onken, J
MLA Citation
Micames, CG, Bentley, R, and Onken, J. "Clinical challenges and images in GI. Invasive candidal enterocolitis." Gastroenterology 133.2 (August 2007): 391-731.
PMID
17681158
Source
pubmed
Published In
Gastroenterology
Volume
133
Issue
2
Publish Date
2007
Start Page
391
End Page
731
DOI
10.1053/j.gastro.2007.06.051

Complete pathological response to bevacizumab and chemoradiation in advanced rectal cancer.

BACKGROUND: Localized rectal cancer responds well to 5-fluorouracil and radiation-based regimens. A phase I-II trial is currently testing the efficacy of adding bevacizumab, a VEGF-specific antibody, to standard chemoradiotherapy. The case presented here is a complete pathological response seen in a patient with extensive and locally invasive carcinoma after receiving this combined treatment. INVESTIGATIONS: Physical examination, rectal ultrasound, PET-CT scan, laboratory tests, proctoscopic examination, chest radiograph, rectal forcep biopsies with immunohistochemistry, and protein and flow cytometric analyses. DIAGNOSIS: Large, invasive, ultrasound stage T4 carcinoma of the rectum, which was positive for survivin. MANAGEMENT: One 2-week cycle of bevacizumab alone, followed by 3 cycles of bevacizumab with continuous 5-fluorouracil infusion, and external-beam radiation therapy given 5 days per week to the pelvis, abdominoperineal resection with posterior vaginectomy, hysterectomy and bilateral salpingo-oophorectomy.

Authors
Willett, CG; Duda, DG; di Tomaso, E; Boucher, Y; Czito, BG; Vujaskovic, Z; Vlahovic, G; Bendell, J; Cohen, KS; Hurwitz, HI; Bentley, R; Lauwers, GY; Poleski, M; Wong, TZ; Paulson, E; Ludwig, KA; Jain, RK
MLA Citation
Willett, CG, Duda, DG, di Tomaso, E, Boucher, Y, Czito, BG, Vujaskovic, Z, Vlahovic, G, Bendell, J, Cohen, KS, Hurwitz, HI, Bentley, R, Lauwers, GY, Poleski, M, Wong, TZ, Paulson, E, Ludwig, KA, and Jain, RK. "Complete pathological response to bevacizumab and chemoradiation in advanced rectal cancer." Nat Clin Pract Oncol 4.5 (May 2007): 316-321.
PMID
17464339
Source
pubmed
Published In
Nature Clinical Practice Oncology
Volume
4
Issue
5
Publish Date
2007
Start Page
316
End Page
321
DOI
10.1038/ncponc0813

Benign endometrial hyperplasia sequence and endometrial intraepithelial neoplasia.

Endometrial "hyperplasia," as currently diagnosed, includes the changes caused by an abnormal hormonal state and those caused by a separate category of monoclonal premalignant disease. The appearance of the disease in these 2 functional categories is discontinuous, permitting more specific diagnosis of the condition using the terms "benign endometrial hyperplasia" and "endometrial intraepithelial neoplasia" (EIN), respectively. Benign endometrial hyperplasia involves the entire endometrial compartment and, with protracted estrogen exposure, shows the progressive development of cysts, remodeled glands, vascular thrombi, and stromal microinfarcts. They are best construed as a sequence of changes whereby the appearance at any single time point is uniquely dependent on the preceding combination and the duration of hormonal exposures. In contrast, the premalignant clone of an EIN lesion is characteristically offset from the background endometrium by its altered cytology and crowded architecture. The use of an internal standard for cytology assessment, combined with the distinctive topography of a clonal process, enables the diagnosis of EIN lesions with a long-term cancer risk 45-fold greater than that of their benign endometrial hyperplasia counterparts. The resolution of hormonal and premalignant subsets of traditional "endometrial hyperplasias" is possible using redefined diagnostic criteria, enabling patient therapy to be appropriately matched with the underlying disease mechanisms.

Authors
Mutter, GL; Zaino, RJ; Baak, JPA; Bentley, RC; Robboy, SJ
MLA Citation
Mutter, GL, Zaino, RJ, Baak, JPA, Bentley, RC, and Robboy, SJ. "Benign endometrial hyperplasia sequence and endometrial intraepithelial neoplasia." Int J Gynecol Pathol 26.2 (April 2007): 103-114. (Review)
PMID
17413975
Source
pubmed
Published In
International Journal of Gynecological Pathology
Volume
26
Issue
2
Publish Date
2007
Start Page
103
End Page
114
DOI
10.1097/PGP.0b013e31802e4696

Three-dimensional imaging of whole rodent organs using optical computed and emission tomography.

We explore the potential of optical computed tomography (optical-CT) and optical emission computed tomography (optical-ECT) in a new area-whole organ imaging. The techniques are implemented on an in-house prototype benchtop system with improved image quality and the capacity to image larger samples (up to 3 cm) than previous systems based on stereo microscopes. Imaging performance tests confirm high geometrical accuracy, accurate relative measurement of linear attenuation coefficients, and the ability to image features at the 50-microm level. Optical labeling of organ microvasculature was achieved using two stains deposited via natural in vivo circulatory processes: a passive absorbing ink-based stain and an active fluorescin FITC-lectin conjugate. The lectin protein binds to the endothelial lining, and FITC fluorescense enables optical-ECT imaging. Three-dimensional (3-D) optical-CT images have been acquired of a normal rat heart and left lung and a mouse right lung showing exquisite detail of the functional vasculature and relative perfusion distribution. Coregistered optical-ECT images were also acquired of the mouse lung and kidney. Histological sections confirmed effective labeling of microvasculature throughout the organs. The advantages of optical-CT and optical-ECT include the potential for a unique combination of high resolution and high contrast and compatibility with a wide variety of optical probes, including gene expression labeling fluorescent reporter proteins.

Authors
Oldham, M; Sakhalkar, H; Wang, YM; Guo, P; Oliver, T; Bentley, R; Vujaskovic, Z; Dewhirst, M
MLA Citation
Oldham, M, Sakhalkar, H, Wang, YM, Guo, P, Oliver, T, Bentley, R, Vujaskovic, Z, and Dewhirst, M. "Three-dimensional imaging of whole rodent organs using optical computed and emission tomography." J Biomed Opt 12.1 (January 2007): 014009-.
PMID
17343484
Source
pubmed
Published In
Journal of Biomedical Optics
Volume
12
Issue
1
Publish Date
2007
Start Page
014009
DOI
10.1117/1.2709858

Primary primitive neuroectodermal tumor of the breast.

Authors
Maxwell, RW; Ghate, SV; Bentley, RC; Soo, MS
MLA Citation
Maxwell, RW, Ghate, SV, Bentley, RC, and Soo, MS. "Primary primitive neuroectodermal tumor of the breast." J Ultrasound Med 25.10 (October 2006): 1331-1333.
PMID
16998107
Source
pubmed
Published In
Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine
Volume
25
Issue
10
Publish Date
2006
Start Page
1331
End Page
1333

Transtubal spread of serous adenocarcinoma of the endometrium: an underrecognized mechanism of metastasis.

Most endometrial carcinomas metastasize by invading myometrial lymphatics and spreading to regional lymph nodes. However, uterine serous carcinomas (USCs) metastasize frequently to peritoneal surfaces even when only minimally invasive. This study examines the methods of spread and the role of retrograde transtubal spread. Eighty-seven USCs treated by hysterectomy were identified. Primary peritoneal cases and cases with significant ovarian involvement were excluded. Eighty (92%) cases were pure serous, and the remainder had at least 25% serous histology. Fifty-four of 87 (62%) had extrauterine spread at hysterectomy, most commonly to peritoneal surfaces and sometimes to the pelvic lymph nodes. Twenty-six of 54 (48%) cases had no lymphatic/vascular (LV) invasion and 18/54 (33%) had no myometrial invasion. Eleven of these 54 (20%) patients with metastases lacked both myometrial and LV invasion, and the metastases involved the peritoneal surface more often than the lymph nodes (p<0.001). Three of the 11 cases had tumor clusters in the fallopian tube lumen. Another 13 cases also had clusters of tumor within the fallopian tube lumen, and all 16 cases had peritoneal spread (p<0.001). Extrauterine spread correlated highly with LV invasion (p<0.001) but not with the presence or depth of myometrial invasion. Retrograde transtubal implantation as well LV invasion are two important mechanisms by which USC spreads; all cases with tumor clusters in the fallopian tube lumen had peritoneal spread. This explains the phenomenon whereby patients with serous carcinomas confined to the endometrium and lacking LV invasion have widespread metastases to the peritoneum.

Authors
Snyder, MJ; Bentley, R; Robboy, SJ
MLA Citation
Snyder, MJ, Bentley, R, and Robboy, SJ. "Transtubal spread of serous adenocarcinoma of the endometrium: an underrecognized mechanism of metastasis." Int J Gynecol Pathol 25.2 (April 2006): 155-160.
PMID
16633065
Source
pubmed
Published In
International Journal of Gynecological Pathology
Volume
25
Issue
2
Publish Date
2006
Start Page
155
End Page
160
DOI
10.1097/01.pgp.0000179614.47838.82

Tissue transglutaminase expression in early-stage cervical cancer

Authors
Rabbani, ZN; Kirkpatrick, JP; Salahuddin, FK; Bentley, RC; Secord, AA; Greenberg, CS; Havrilesky, LJ; Vujaskovic, Z; Jones, E; Dewhirst, MW
MLA Citation
Rabbani, ZN, Kirkpatrick, JP, Salahuddin, FK, Bentley, RC, Secord, AA, Greenberg, CS, Havrilesky, LJ, Vujaskovic, Z, Jones, E, and Dewhirst, MW. "Tissue transglutaminase expression in early-stage cervical cancer." 2006.
Source
wos-lite
Published In
International Journal of Radiation Oncology, Biology, Physics
Volume
66
Issue
3
Publish Date
2006
Start Page
S167
End Page
S167
DOI
10.1016/j.ijrobp.2006.07.331

Anthropometric measurements and epithelial ovarian cancer risk in African-American and White women.

Previous studies of anthropometric factors and ovarian cancer risk have been inconsistent and none have evaluated the association among African-American women. Data from a population-based, case-control study of 593 cases and 628 controls were used to evaluate ovarian cancer risk in relation to weight, height, body mass index (BMI) and waist-to-hip ratio (WHR). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed and established risk factors were adjusted for using logistic regression models, stratified by race. Among all races, weight at age 18, WHR, weight and BMI one year prior to interview were associated with elevated ovarian cancer risk. When stratified by race, the association between WHR and ovarian was similar among Whites and among African Americans. However, African-American women in the fourth quartile of height had an elevated risk of ovarian cancer (OR = 3.2; 95% CI = 1.3-7.8), but this risk was not apparent in Whites (OR = 1.0; 95% CI = 0.7-1.4). These findings support the hypothesis that obesity is an important risk factor of ovarian cancer among African-Americans and Whites and also suggest that height may be a risk factor specific to African-Americans.

Authors
Hoyo, C; Berchuck, A; Halabi, S; Bentley, RC; Moorman, P; Calingaert, B; Schildkraut, JM
MLA Citation
Hoyo, C, Berchuck, A, Halabi, S, Bentley, RC, Moorman, P, Calingaert, B, and Schildkraut, JM. "Anthropometric measurements and epithelial ovarian cancer risk in African-American and White women." Cancer Causes Control 16.8 (October 2005): 955-963.
PMID
16132804
Source
pubmed
Published In
Cancer Causes & Control
Volume
16
Issue
8
Publish Date
2005
Start Page
955
End Page
963
DOI
10.1007/s10552-005-3205-y

Longitudinal mechanical tension induces growth in the small bowel of juvenile rats.

INTRODUCTION: The aim of our study was to apply longitudinal force to the small bowel to increase the length of intestine in juvenile rats. METHODS: Fifty juvenile rats had double barrelled, blind loop ostomies created using an isolated segment of bowel. Our intestinal lengthening device was inserted into one of the loops and the second loop served as a control. Once the device was deployed, the experimental, control, and in situ segments of bowel were evaluated for length, weight, histology, and disaccharidase enzyme activity. RESULTS: Mechanical tension increased intestinal length by 149%. The lengthened bowel also exhibited a greater total weight (218%), greater mucosal weight (122%), and increased protein mass (164%) compared with the control limb of bowel. Histologically, there was a markedly increased thickness of the muscularis propria in the lengthened bowel (200% increase compared with the control limb). Functionally, we found increased total disaccharidase activity in the lengthened bowel (between 47% and 350%, depending on the particular enzyme tested; p<0.01). CONCLUSION: Mechanical tension induces intestinal growth by increasing length, weight of the bowel and mucosa, and protein mass. Histological changes, such as increases in Paneth cells, suggest that increased proliferation and reorganisation of the mucosa and muscularis propria are a response to mechanical tension. Functionally, increased intestinal length corresponds with increased disaccharidase activity, thus implying potential increased absorptive capacity of the lengthened bowel.

Authors
Safford, SD; Freemerman, AJ; Safford, KM; Bentley, R; Skinner, MA
MLA Citation
Safford, SD, Freemerman, AJ, Safford, KM, Bentley, R, and Skinner, MA. "Longitudinal mechanical tension induces growth in the small bowel of juvenile rats." Gut 54.8 (August 2005): 1085-1090.
PMID
15840689
Source
pubmed
Published In
Gut
Volume
54
Issue
8
Publish Date
2005
Start Page
1085
End Page
1090
DOI
10.1136/gut.2004.061481

Genetic modeling of human rhabdomyosarcoma.

Rhabdomyosarcoma, a malignancy showing features of skeletal muscle differentiation, is the most common soft tissue sarcoma of childhood. The identification of distinct clinical presentation patterns, histologic tumor types, and risk groups suggests that rhabdomyosarcoma is a collection of highly related sarcomas rather than a single entity. In an effort to understand this seemingly heterogeneous malignancy, we constructed a genetically defined but malleable model of rhabdomyosarcoma by converting less differentiated human skeletal muscle cell precursors (SkMC) and committed human skeletal muscle myoblasts (HSMM) into their malignant counterparts by targeting pathways altered in rhabdomyosarcoma. Whereas the two cell types were both tumorigenic, SkMCs gave rise to highly heterogeneous tumors occasionally displaying features of rhabdomyosarcoma, whereas HSMMs formed rhabdomyosarcoma-like tumors with an embryonal morphology, capable of invasion and metastasis. Thus, despite introducing the same panel of genetic changes, altering the skeletal muscle cell of origin led to different tumor morphologies, suggesting that cell of origin may dictate rhabdomyosarcoma tumor histology. The ability to now genetically induce human rhabdomyosarcoma-like tumors provides a representative model to dissect the molecular mechanisms underlying this cancer.

Authors
Linardic, CM; Downie, DL; Qualman, S; Bentley, RC; Counter, CM
MLA Citation
Linardic, CM, Downie, DL, Qualman, S, Bentley, RC, and Counter, CM. "Genetic modeling of human rhabdomyosarcoma." Cancer Res 65.11 (June 1, 2005): 4490-4495.
PMID
15930263
Source
pubmed
Published In
Cancer Research
Volume
65
Issue
11
Publish Date
2005
Start Page
4490
End Page
4495
DOI
10.1158/0008-5472.CAN-04-3194

Transforming growth factor beta receptor I polyalanine repeat polymorphism does not increase ovarian cancer risk.

OBJECTIVES: It has been suggested that the 6A allele of the type I TGFbeta receptor (TGFbetaR1) polyalanine repeat tract polymorphism may increase susceptibility to various types of cancer including ovarian cancer. METHODS: The TGFbetaR1 polyalanine polymorphism was genotyped in 588 ovarian cancer cases and 614 controls from a population-based case-control study in North Carolina. RESULTS: Significant racial differences in the frequency of the 6A allele were observed between Caucasian (10.7%) and African-American (2.4%) controls (P < 0.001). One or two copies of the 6A allele of the TGFbetaR1 polyalanine polymorphism was carried by 18% of all controls and 19% of cases, and there was no association with ovarian cancer risk (OR = 1.07, 95% CI 0.80-1.44). The odds ratio for 6A homozygotes was 1.81 (95% CI 0.655.06), but these comprised only 0.98% of controls and 1.70% of cases. CONCLUSIONS: The 6A allele of the TGFbetaR1 polyalanine polymorphism does not appear to increase ovarian cancer risk. Larger studies would be needed to exclude the possibility that the small fraction of individuals who are 6A homozygotes have an increased risk of ovarian or other cancers.

Authors
Spillman, MA; Schildkraut, JM; Halabi, S; Moorman, P; Calingaert, B; Bentley, RC; Marks, JR; Murphy, S; Berchuck, A
MLA Citation
Spillman, MA, Schildkraut, JM, Halabi, S, Moorman, P, Calingaert, B, Bentley, RC, Marks, JR, Murphy, S, and Berchuck, A. "Transforming growth factor beta receptor I polyalanine repeat polymorphism does not increase ovarian cancer risk." Gynecol Oncol 97.2 (May 2005): 543-549.
PMID
15863158
Source
pubmed
Published In
Gynecologic Oncology
Volume
97
Issue
2
Publish Date
2005
Start Page
543
End Page
549
DOI
10.1016/j.ygyno.2005.01.025

Acoustic radiation force impulse (ARFI) imaging of the gastrointestinal tract.

The evaluation of lesions in the gastrointestinal (GI) tract using ultrasound can suffer from poor contrast between healthy and diseased tissue. Acoustic Radiation Force Impulse (ARFI) imaging provides information about the mechanical properties of tissue using brief, high-intensity, focused ultrasound to generate radiation force and ultrasonic correlation-based methods to track the resulting tissue displacement. Using conventional linear arrays, ARFI imaging has shown improved contrast over B-mode images when applied to solid masses in the breast and liver. The purpose of this work is to (1) investigate the potential for ARFI imaging to provide improvements over conventional B-mode imaging of GI lesions and (2) demonstrate that ARFI imaging can be performed with an endocavity probe. ARFI images of an adenocarcinoma of the gastroesophageal (GE) junction, status-post chemotherapy and radiation treatment, demonstrate better contrast between healthy and fibrotic/malignant tissue than standard B-mode images. ARFI images of healthy gastric, esophageal, and colonic tissue specimens differentiate normal anatomic tissue layers (i.e., mucosal, muscularis and adventitial layers), as confirmed by histologic evaluation. ARFI imaging of ex vivo colon and small bowel tumors portray interesting contrast and structure that are not as well defined in B-mode images. An endocavity probe created ARFI images to a depth of over 2 cm in tissue-mimicking phantoms, with maximum displacements of 4 microm. These findings support the clinical feasibility of endocavity ARFI imaging to guide diagnosis and staging of disease processes in the GI tract.

Authors
Palmeri, ML; Frinkley, KD; Zhai, L; Gottfried, M; Bentley, RC; Ludwig, K; Nightingale, KR
MLA Citation
Palmeri, ML, Frinkley, KD, Zhai, L, Gottfried, M, Bentley, RC, Ludwig, K, and Nightingale, KR. "Acoustic radiation force impulse (ARFI) imaging of the gastrointestinal tract." Ultrason Imaging 27.2 (April 2005): 75-88.
PMID
16231837
Source
pubmed
Published In
Ultrasonic Imaging
Volume
27
Issue
2
Publish Date
2005
Start Page
75
End Page
88
DOI
10.1177/016173460502700202

Decreased E-cadherin expression correlates with higher stage of Wilms' tumors.

PURPOSE: The aim of this study was to examine the association between E-cadherin expression and markers of Wilms' tumor aggression, including metastasis and recurrence. METHODS: Forty Wilms' tumor samples from the National Wilms' Tumor Study Group underwent immunohistochemical staining for E-cadherin. Tumor stage at diagnosis, recurrence, and loss of heterozygosity at 16q status was known for each of the tumor samples. E-Cadherin cell staining was defined as high (>33%) or low (<33%), and values were assigned by a pathologist blinded to the tumor characteristics. Five stage IV tumors were ineligible for assay because of lack of a tubular component. To identify a mechanism of downregulation, we screened tumor DNA for genetic mutations in exons 1-16 using a combination of WAVE and sequence analysis. To assess the functional significance of the identified mutations, the authors compared amino acid homology across multiple species. Finally, they performed reverse transcriptase-polymerase chain reaction for those tumors with intronic single nucleotide polymorphisms (SNPs) to evaluate for mRNA splice variants. RESULTS: Wilms' tumors presenting with metastatic (stage IV) disease demonstrated decreased levels of E-cadherin expression compared with localized tumors (stage I) (Fisher's Exact test, P < .01). In a search for the mechanism of the downregulation of E-cadherin, we identified 5 different mutations in 7 high stage tumors (7/15) and 1 mutation in a low stage tumor (1/20). The mutations occurred in amino acids that were conserved across multiple species. Additionally, 11 of 15 high stage tumors contained an intronic SNP located within 6 bp of the 5 intronic splice junction immediately downstream of exon 1. However, examination of 5 of these tumors using reverse transcriptase-polymerase chain reaction showed that this intronic SNP does not appear to disrupt the assembly of full-length E-cadherin transcripts. Lastly, no correlation was identified between E-cadherin expression and recurrence of disease. CONCLUSIONS: In this study, the authors have found an association between decreased E-cadherin expression and metastatic Wilms' tumor. Mutations identified may help identify a mechanism for downregulation. The functional significance of these mutations is supported by the conserved nature of the amino acids across multiple species. The authors believe these findings support the involvement of E-cadherin in the evolution of Wilms' tumor.

Authors
Safford, SD; Freemerman, AJ; Langdon, S; Bentley, R; Goyeau, D; Grundy, PE; Skinner, MA
MLA Citation
Safford, SD, Freemerman, AJ, Langdon, S, Bentley, R, Goyeau, D, Grundy, PE, and Skinner, MA. "Decreased E-cadherin expression correlates with higher stage of Wilms' tumors." J Pediatr Surg 40.2 (February 2005): 341-348.
PMID
15750927
Source
pubmed
Published In
Journal of Pediatric Surgery
Volume
40
Issue
2
Publish Date
2005
Start Page
341
End Page
348
DOI
10.1016/j.jpedsurg.2004.10.030

Retrograde transtubal spread in extra-uterine metastasis of uterine serous carcinoma

Authors
Snyder, MJ; Bentley, RC; Lutman, C; Robboy, SJ
MLA Citation
Snyder, MJ, Bentley, RC, Lutman, C, and Robboy, SJ. "Retrograde transtubal spread in extra-uterine metastasis of uterine serous carcinoma." January 2005.
Source
wos-lite
Published In
Laboratory Investigation
Volume
85
Publish Date
2005
Start Page
204A
End Page
205A

Retrograde transtubal spread in extra-uterine metastasis of uterine serous carcinoma

Authors
Snyder, MJ; Bentley, RC; Lutman, C; Robboy, SJ
MLA Citation
Snyder, MJ, Bentley, RC, Lutman, C, and Robboy, SJ. "Retrograde transtubal spread in extra-uterine metastasis of uterine serous carcinoma." January 2005.
Source
wos-lite
Published In
Modern Pathology
Volume
18
Publish Date
2005
Start Page
204A
End Page
205A

Acoustic radiation force impulse imaging of the mechanical properties of arteries: in vivo and ex vivo results.

We present results of a pilot study of ex vivo and in vivo acoustic radiation force impulse (ARFI) imaging demonstrating measurements of the mechanical properties of the carotid and popliteal arteries. The results were obtained on a modified commercial scanner, providing coregistered B-mode and color Doppler images. 2D and 1D through time images are formed from the measurements of tissues' response to very brief and localized applications of radiation force. The images show good correlation with B-mode and, in ex vivo studies, pathology-based characterizations of vessel geometry and plaque stiffness. In vivo measurements of arterial response during both systole and diastole are presented. We address implementation issues and discuss potential applications of this new vascular imaging method.

Authors
Trahey, GE; Palmeri, ML; Bentley, RC; Nightingale, KR
MLA Citation
Trahey, GE, Palmeri, ML, Bentley, RC, and Nightingale, KR. "Acoustic radiation force impulse imaging of the mechanical properties of arteries: in vivo and ex vivo results." Ultrasound Med Biol 30.9 (September 2004): 1163-1171.
PMID
15550320
Source
pubmed
Published In
Ultrasound in Medicine & Biology
Volume
30
Issue
9
Publish Date
2004
Start Page
1163
End Page
1171
DOI
10.1016/j.ultrasmedbio.2004.07.022

Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study.

BACKGROUND: This study was performed to determine whether 24-h paclitaxel plus doxorubicin and filgrastim was superior to cisplatin plus doxorubicin in patients with endometrial cancer with respect to response, progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: Eligible chemotherapy-naïve patients were randomly assigned to doxorubicin 60 mg/m2 intravenously (i.v.) followed by cisplatin 50 mg/m2 i.v. (arm 1, n=157) or doxorubicin 50 mg/m2 i.v. followed 4 h later by paclitaxel 150 mg/m2 i.v. over 24 h plus filgrastim 5 microg/kg on days 3-12 (arm 2, n=160). Starting doses were reduced for prior pelvic radiotherapy and age > 65 years. Both regimens were to be repeated every 3 weeks for a maximum of seven cycles. RESULTS: There was no significant difference in response rate (40% versus 43%), PFS (median 7.2 versus 6 months) or OS (median 12.6 versus 13.6 months) for arm 1 and arm 2, respectively. Toxicities were primarily hematological, with 54% (arm 1) and 50% (arm 2) of patients experiencing grade 4 granulocytopenia. Gastrointestinal toxicities were similar in both arms. CONCLUSIONS: Doxorubicin and 24-h paclitaxel plus filgrastim was not superior to doxorubicin and cisplatin in terms of response, PFS or survival in advanced endometrial cancer.

Authors
Fleming, GF; Filiaci, VL; Bentley, RC; Herzog, T; Sorosky, J; Vaccarello, L; Gallion, H
MLA Citation
Fleming, GF, Filiaci, VL, Bentley, RC, Herzog, T, Sorosky, J, Vaccarello, L, and Gallion, H. "Phase III randomized trial of doxorubicin + cisplatin versus doxorubicin + 24-h paclitaxel + filgrastim in endometrial carcinoma: a Gynecologic Oncology Group study." Ann Oncol 15.8 (August 2004): 1173-1178.
PMID
15277255
Source
pubmed
Published In
Annals of Oncology
Volume
15
Issue
8
Publish Date
2004
Start Page
1173
End Page
1178
DOI
10.1093/annonc/mdh316

HER-2 gene amplification correlates with higher levels of angiogenesis and lower levels of hypoxia in primary breast tumors.

PURPOSE: This study investigated the connection among HER-2 gene amplification, HER-2 protein expression, and markers of tumor angiogenesis and oxygenation in patients with operable, invasive breast tumors. EXPERIMENTAL DESIGN: From 1988 to 1995, 425 patients with metastatic breast cancer were enrolled in a study of high-dose chemotherapy with autologous transplant. Primary tumor blocks were obtained and evaluated using immunohistochemistry (IHC) staining of vessels with von Willebrand factor antibody. Mean microvessel densities (MVD) were determined by counting von Willebrand factor stained cells in three separate "vascular hot spots" using image analysis. Tumor samples were also stained for HER-2 by IHC, HER-2 gene amplification by fluorescence in situ hybridization, carbonic anhydrase 9 by IHC, and vascular endothelial growth factor (VEGF) by IHC. Plasma from 36 patients with primary tumor samples had VEGF (R&D Systems, MN) and d-dimer (American Diagnostica, Greenwich, CT) levels determined. RESULTS: There was a significant positive correlation between HER-2 gene amplification and both maximum and average MVD (Spearman coefficient = 0.51 and 0.50; P = 0.03 and 0.05, respectively). There was an inverse correlation with HER-2 gene amplification and expression of the tumor hypoxia marker CA-9 (chi(2) P = 0.02). The level of HER-2 gene amplification correlated with plasma d-dimer levels (Spearman coefficient = 0.43; P = 0.021). Interestingly, tumors with HER-2 by IHC had decreased amounts of VEGF staining (chi(2) = 5.81; P = 0.01). There was no correlation between HER-2 by IHC and MVD or d-dimer. Of all of the variables examined, only average (P = 0.0016) and maximum MVD (P = 0.0128) predicted disease-free survival (Cox univariate model). CONCLUSIONS: HER-2-amplified breast cancers have increased amounts of angiogenesis, decreased amounts of hypoxia, and increased markers of fibrin degradation. These findings have prognostic, predictive, and therapeutic implications in breast cancer treatment.

Authors
Blackwell, KL; Dewhirst, MW; Liotcheva, V; Snyder, S; Broadwater, G; Bentley, R; Lal, A; Riggins, G; Anderson, S; Vredenburgh, J; Proia, A; Harris, LN
MLA Citation
Blackwell, KL, Dewhirst, MW, Liotcheva, V, Snyder, S, Broadwater, G, Bentley, R, Lal, A, Riggins, G, Anderson, S, Vredenburgh, J, Proia, A, and Harris, LN. "HER-2 gene amplification correlates with higher levels of angiogenesis and lower levels of hypoxia in primary breast tumors." Clin Cancer Res 10.12 Pt 1 (June 15, 2004): 4083-4088.
PMID
15217943
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
10
Issue
12 Pt 1
Publish Date
2004
Start Page
4083
End Page
4088
DOI
10.1158/1078-0432.CCR-03-0695

Radical hysterectomy and pelvic lymphadenectomy for stage IB2 cervical cancer.

OBJECTIVE: We wished to evaluate survival and adverse outcomes of patients with stage IB2 cervical cancer treated primarily with radical hysterectomy and lymphadenectomy. METHODS: A review was performed of all patients undergoing primary radical hysterectomy for stage IB2 cervical cancer at two institutions from 1987 to 2002. Patients were stratified into low, intermediate (Gynecologic Oncology Group protocol 92 criteria), and high-risk (positive nodes, margins, or parametria) groups. Survival and progression-free interval were analyzed using the Kaplan-Meier method and multivariate analysis. RESULTS: Seventy-two patients underwent primary type III radical hysterectomy and lymphadenectomy (72 pelvic, 58 pelvic and paraaortic). Patients were classified as low (n = 6), intermediate (n = 49), or high (n = 17) risk for recurrence. Adjuvant therapy was administered to 94%, 12%, and 0% of the high-, intermediate-, and low-risk groups, respectively. Five-year survival was 72%, while 5-year progression-free survival was 63%. Five-year overall and progression-free survival by risk group were 47% and 40% (high-risk), 80% and 66% (intermediate-risk), 100% and 100% (low-risk). Predictors of survival in multivariate analysis were Caucasian race (P = 0.001), older age (P = 0.017), inner 2/3 cervical wall invasion (P = 0.045), and absence of lymph-vascular invasion (P < 0.001). Major complications were experienced by 10/72 (13.9%) patients. Among 34 patients who received radiation therapy, two (5.9%) experienced complications attributable to radiation. CONCLUSIONS: Radical hysterectomy and lymphadenectomy followed by tailored adjuvant therapy is a reasonable alternative to primary radiotherapy for stage IB2 cervical cancer. Patients with low- and intermediate-risk factors have satisfactory results after primary surgical management. A prospective randomized trial will clarify the optimal mode of initial therapy for patients with stage IB2 disease.

Authors
Havrilesky, LJ; Leath, CA; Huh, W; Calingaert, B; Bentley, RC; Soper, JT; Alvarez Secord, A
MLA Citation
Havrilesky, LJ, Leath, CA, Huh, W, Calingaert, B, Bentley, RC, Soper, JT, and Alvarez Secord, A. "Radical hysterectomy and pelvic lymphadenectomy for stage IB2 cervical cancer." Gynecol Oncol 93.2 (May 2004): 429-434.
PMID
15099957
Source
pubmed
Published In
Gynecologic Oncology
Volume
93
Issue
2
Publish Date
2004
Start Page
429
End Page
434
DOI
10.1016/j.ygyno.2004.01.038

Estrogen receptor alpha (ESR1) mutant A908G is not a common feature in benign and malignant proliferations of the breast.

Alterations in estrogen responsive pathways are thought to contribute to benign and malignant breast disease. It has been reported previously that more than a third of typical epithelial hyperplasia lesions harbor the missense mutation A908G in the estrogen receptor alpha (ESR1) gene. This substitution of an arginine for a lysine at codon 303 was reported to confer mitogenic hypersensitivity to estrogen. To explore this finding further, we analyzed ESR1 for this mutation in a series of breast tissues ranging from typical hyperplasia to invasive cancer. In contrast to previous studies, no evidence for this mutation was found in 36 invasive cancers, 11 in situ carcinomas, 14 epithelial hyperplasias with atypia, 11 epithelial hyperplasias without atypia, and 11 breast cancer cell lines. These results indicate that ESR1 mutant A908G does not occur with significant frequency in either benign or malignant proliferations of breast epithelia.

Authors
Tebbit, CL; Bentley, RC; Olson, JA; Marks, JR
MLA Citation
Tebbit, CL, Bentley, RC, Olson, JA, and Marks, JR. "Estrogen receptor alpha (ESR1) mutant A908G is not a common feature in benign and malignant proliferations of the breast." Genes Chromosomes Cancer 40.1 (May 2004): 51-54.
PMID
15034868
Source
pubmed
Published In
Genes, Chromosomes and Cancer
Volume
40
Issue
1
Publish Date
2004
Start Page
51
End Page
54
DOI
10.1002/gcc.20017

Acoustic Radiation Force Impulse (ARFI) imaging of the gastrointestinal tract

Currently, the evaluation of lesions in the gastrointestinal (GI) tract using ultrasound suffers from poor contrast between healthy and diseased tissue. Acoustic Radiation Force Impulse (ARFI) imaging provides information about the mechanical properties of tissue using brief, high-intensity, focused ultrasound to generate radiation force, and conventional, ultrasonic, correlation-based methods to track tissue displacement. Using conventional linear arrays, ARFI imaging has shown improved contrast over B-mode images when applied to solid masses in the breast and liver. The purpose of this work is to (1) demonstrate that ARFI imaging can be performed with an endocavity probe, and (2) demonstrate that ARFI imaging can provide improvements over conventional B-mode imaging of GI lesions. An EC94, 6.2 MHz, endocavity probe was modified to perform ARFI imaging in tissue-mimicking phantoms using a Siemens SONOLINE Antares scanner. ARFI imaging was performed on fresh, surgically-excised, GI lesions using a 75L40, 7.2 MHz, linear array on a modified Siemens SONOLINE Elegra™ scanner. The endocavity probe created ARFI images to a depth of over 2 cm in tissue-mimicking phantoms, with maximum displacements of 5 μm. The endocavity probe did not heat appreciably during ARFI imaging, demonstrating that the probe's small size will not limit in vivo ARFI imaging. ARFI images of an adenocarcinoma of the gastroesophageal (GE) junction, status-post chemotherapy and radiation treatment, demonstrate better contrast between healthy and fibrotic/malignant tissue than standard B-mode images. ARFI images of healthy gastric, esophageal, and colonic tissue specimens differentiate normal anatomic tissue planes (i.e., mucosal, muscularis, and adventitial layers), as confirmed by histologic evaluation. ARFI imaging of an ex vivo colon cancer portrays interesting contrast and structure not present in B-mode images. These findings support the clinical feasibility of endoscopic ARFI imaging to guide diagnosis and staging of disease processes in the GI tract. © 2004 IEEE.

Authors
Palmeri, M; Frinkley, K; Zhai, L; Bentley, R; Ludwig, K; Gottfried, M; Nightingale, K
MLA Citation
Palmeri, M, Frinkley, K, Zhai, L, Bentley, R, Ludwig, K, Gottfried, M, and Nightingale, K. "Acoustic Radiation Force Impulse (ARFI) imaging of the gastrointestinal tract." 2004.
Source
scival
Published In
Proceedings of the IEEE Ultrasonics Symposium
Volume
1
Publish Date
2004
Start Page
744
End Page
747

Accuracy of MRI in the detection of residual breast cancer after neoadjuvant chemotherapy.

OBJECTIVE: This study was undertaken to evaluate the ability of MRI to accurately show residual primary breast malignancy in women treated with neoadjuvant chemotherapy. MATERIALS AND METHODS: Twenty-one patients with locally advanced primary breast carcinoma underwent contrast-enhanced MRI before and after treatment with neoadjuvant anthracycline-based chemotherapy. For each patient, the maximum extent of the MRI abnormality was measured both before and after treatment. These measurements were subsequently compared with physical examination findings and histologic results to determine the ability of MRI to accurately reveal tumor extent after neoadjuvant chemotherapy. RESULTS: MRI after chemotherapy showed a correlation coefficient of 0.75 with histology, which was better than physical examination (r = 0.61). MRI underestimated the extent of residual tumor in two patients by more than 1 cm (including one false-negative examination), was within 1 cm in 12 of 21 patients, and overestimated tumor extent by more than 1 cm in seven of 21 patients. CONCLUSION: MRI can show residual malignancy after neoadjuvant chemotherapy better than physical examination, particularly in patients who have not had a complete clinical response to therapy.

Authors
Rosen, EL; Blackwell, KL; Baker, JA; Soo, MS; Bentley, RC; Yu, D; Samulski, TV; Dewhirst, MW
MLA Citation
Rosen, EL, Blackwell, KL, Baker, JA, Soo, MS, Bentley, RC, Yu, D, Samulski, TV, and Dewhirst, MW. "Accuracy of MRI in the detection of residual breast cancer after neoadjuvant chemotherapy." AJR Am J Roentgenol 181.5 (November 2003): 1275-1282.
PMID
14573420
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
181
Issue
5
Publish Date
2003
Start Page
1275
End Page
1282
DOI
10.2214/ajr.181.5.1811275

Polymorphisms in BRCA1 and BRCA2 and risk of epithelial ovarian cancer.

PURPOSE: Because inherited BRCA1 or BRCA2 mutations strikingly increase ovarian cancer risk, polymorphisms in these genes could represent low penetrance susceptibility alleles. Previous studies of the BRCA2 N372H polymorphism suggested that HH homozygotes have a modestly increased risk of both breast and ovarian cancer. We have examined whether BRCA2 N372H or common amino acid-changing polymorphisms in BRCA1 predispose to ovarian cancer. EXPERIMENTAL DESIGN: A population-based, case control study of ovarian cancer was performed in North Carolina. Cases included 312 women with ovarian cancer (76% invasive and 24% borderline) and 401 age- and race-matched controls. Blood DNA from subjects was genotyped for BRCA2 N372H and BRCA1 Q356R and P871L. RESULTS: There was no association between BRCA2 N372H and risk of borderline or invasive epithelial ovarian cancer. The overall odds ratio (OR) for HH homozygotes was 0.8 [95% confidence interval (CI) = 0.4-1.5] and was similar in all subsets, including invasive serous cases. In addition, neither the BRCA1 Q356R (OR = 0.9, 95% CI 0.5-1.4) nor P871L (OR = 0.9, 95% CI 0.6-1.9) polymorphisms were associated with ovarian cancer risk. There was a significant racial difference in allele frequencies of the P871L polymorphism (P = 0.64 in Caucasians, L = 0.76 in African-Americans, P < 0.0001). CONCLUSIONS: In this population-based, case control study, common amino acid changing BRCA1 and 2 polymorphisms were not found to affect the risk of developing ovarian cancer.

Authors
Wenham, RM; Schildkraut, JM; McLean, K; Calingaert, B; Bentley, RC; Marks, J; Berchuck, A
MLA Citation
Wenham, RM, Schildkraut, JM, McLean, K, Calingaert, B, Bentley, RC, Marks, J, and Berchuck, A. "Polymorphisms in BRCA1 and BRCA2 and risk of epithelial ovarian cancer." Clin Cancer Res 9.12 (October 1, 2003): 4396-4403.
PMID
14555511
Source
pubmed
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
9
Issue
12
Publish Date
2003
Start Page
4396
End Page
4403

Pathology of gestational trophoblastic disease.

Authors
Bentley, RC
MLA Citation
Bentley, RC. "Pathology of gestational trophoblastic disease." Clin Obstet Gynecol 46.3 (September 2003): 513-522. (Review)
PMID
12972734
Source
pubmed
Published In
Clinical Obstetrics and Gynecology
Volume
46
Issue
3
Publish Date
2003
Start Page
513
End Page
522

Matrix metalloproteinase-1 gene promoter polymorphism and risk of ovarian cancer.

OBJECTIVE: It has been suggested that the 2G allele of a guanine insertion-deletion promoter polymorphism in the promoter of the matrix metalloproteinase-1 (MMP1) gene may increase susceptibility to ovarian cancer. The 2G allele also has been associated with increased MMP1 expression. We investigated the relationship between the MMP1 polymorphism and ovarian cancer risk in a large population-based, case-control study. METHODS: The MMP1 promoter polymorphism was examined in white blood cell DNA from 311 cases and 387 age- and race-matched controls using a radiolabeled polymerase chain reaction assay. In addition, genotyping of the MMP1 polymorphism performed in 42 advanced-stage invasive serous ovarian cancers was compared to their mean relative MMP1 expression from Affymetrix microarrays. RESULTS: The 2G allele frequency did not differ significantly between cases (0.49) and controls (0.48), and the distribution of genotypes was in Hardy-Weinberg equilibrium. Using 1G homozygotes as the reference group, neither 2G homozygotes (odds ratio 1.1, 95% confidence interval 0.7-1.7) nor heterozygotes plus 2G homozygotes (odds ratio 0.9, 95% confidence interval 0.7-1.3) had an increased risk of ovarian cancer. There was also no relationship between MMP1 genotype and histologic grade, histologic type, stage, or tumor behavior (borderline versus invasive). The mean MMP1 expression was twice as high in 2G homozygotes relative to 1G homozygotes, but this difference was not statistically significant. CONCLUSION: The reported association between the MMP1 promoter polymorphism and ovarian cancer risk was not supported by our data. There was a suggestion that the 2G allele may be associated with higher MMP1 expression, and this finding is worthy of further investigation.

Authors
Wenham, RM; Calingaert, B; Ali, S; McClean, K; Whitaker, R; Bentley, R; Lancaster, JM; Schildkraut, J; Marks, J; Berchuck, A
MLA Citation
Wenham, RM, Calingaert, B, Ali, S, McClean, K, Whitaker, R, Bentley, R, Lancaster, JM, Schildkraut, J, Marks, J, and Berchuck, A. "Matrix metalloproteinase-1 gene promoter polymorphism and risk of ovarian cancer." J Soc Gynecol Investig 10.6 (September 2003): 381-387.
PMID
12969782
Source
pubmed
Published In
Journal of the Society for Gynecologic Investigation (Elsevier)
Volume
10
Issue
6
Publish Date
2003
Start Page
381
End Page
387

Increased sectioning of pathologic specimens with ductal carcinoma in situ of the breast: are there clinical consequences?

To assess if there has been increased sectioning of pathologic specimens with ductal carcinoma in situ (DCIS), identify sources of this change, and consider the clinical consequences, pathologic data from patients who underwent initial excisional biopsies at our institution and were referred to the radiation oncology department with DCIS from 1992-2002 were retrospectively reviewed. One hundred forty-four of 480 patients with DCIS were eligible for review. Specimen size was recorded as length, to the nearest 0.1 cm, in 3 dimensions. Specimen volume was approximated by the product of the 3 dimensions of the specimen. The primary endpoint was the number of microscopic sections taken from gross specimens, corrected for specimen size. Other analysis included margin status, use of a previous stereotactic needle biopsy, and whether a subsequent repeat excision was performed. Over time, there was an increase in size of the excisional biopsy specimens (mean of 49 cm3 from 1992 to 1994 and 90 cm3 from 2001 to 2002; P = 0.045). Mean numbers of slides per centimeter of specimen were 2.5, 2.7, 3.9, and 5.8 for the intervals 1992-1994, 1995-1997, 1998-2000, and 2001-2002, respectively (P < 0.001 for 1992-1997 vs. 1998-2002). Adjusting for volume, the increase over time in the number of slides per specimen was statistically significant (parameter significance, P < 0.001). For a given volume, the number of slides increased approximately 9.1% per year, on average, during the study period. The positive margin rates were 52%, 46%, 23%, and 25% from 1992 to 1994, from 1995 to 1997, from 1998 to 2000, and from 2001 to 2002, respectively. The degree of sectioning, corrected for specimen length and volume, increased over time.

Authors
Miller, KL; Marks, LB; Barrier, RC; Leight, GS; Clough, RW; Prosnitz, RG; Bentley, RC
MLA Citation
Miller, KL, Marks, LB, Barrier, RC, Leight, GS, Clough, RW, Prosnitz, RG, and Bentley, RC. "Increased sectioning of pathologic specimens with ductal carcinoma in situ of the breast: are there clinical consequences?." Clin Breast Cancer 4.3 (August 2003): 198-202.
PMID
14499013
Source
pubmed
Published In
Clinical Breast Cancer
Volume
4
Issue
3
Publish Date
2003
Start Page
198
End Page
202

No relationship between ovarian cancer risk and progesterone receptor gene polymorphism in a population-based, case-control study in North Carolina.

Authors
Lancaster, JM; Wenham, RM; Halabi, S; Calingaert, B; Marks, JR; Moorman, PG; Bentley, RC; Berchuck, A; Schildkraut, JM
MLA Citation
Lancaster, JM, Wenham, RM, Halabi, S, Calingaert, B, Marks, JR, Moorman, PG, Bentley, RC, Berchuck, A, and Schildkraut, JM. "No relationship between ovarian cancer risk and progesterone receptor gene polymorphism in a population-based, case-control study in North Carolina." Cancer Epidemiol Biomarkers Prev 12.3 (March 2003): 226-227.
PMID
12646513
Source
pubmed
Published In
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Volume
12
Issue
3
Publish Date
2003
Start Page
226
End Page
227

Fine mapping of Wilms' tumors with 16q loss of heterozygosity localizes the putative tumor suppressor gene to a region of 6.7 megabases.

BACKGROUND: The aim of this study was to more precisely map the region of 16q loss of heterozygosity (LOH) in Wilms' tumors and to examine the expression of putative tumor suppressor. METHODS: We performed polymerase chain reaction-based LOH analysis on the 185 sample pairs from 21 to 80 megabases (Mb) on chromosome 16q. Expression of two candidate tumor suppressor genes located within the identified consensus region of 16q LOH was examined by immunohistochemistry. RESULTS: We identified 16q LOH in 7 (4%) of 185 Wilms' tumors not previously thought to demonstrate such genetic loss. The smallest common region of genetic loss was located between 67.3 and 74.0 Mb on chromosome 16. Within this 6.7-Mb region, there reside only three recognized tumor suppressor genes: E-cadherin, P-cadherin, and E2F4. E-cadherin demonstrates statistically significantly reduced expression in Wilms' tumors with 16q LOH. CONCLUSIONS: We have localized the consensus region of 16q LOH in Wilms' tumor to a 6.7-Mb locus and have identified three candidate Wilms' tumor suppressor genes within this narrowed region. Our data support E-cadherin as a candidate tumor suppressor gene in Wilms' tumor; however, further studies are needed to definitively prove its role as the tumor suppressor gene associated with 16q LOH.

Authors
Safford, SD; Goyeau, D; Freemerman, AJ; Bentley, R; Everett, ML; Grundy, PE; Skinner, MA
MLA Citation
Safford, SD, Goyeau, D, Freemerman, AJ, Bentley, R, Everett, ML, Grundy, PE, and Skinner, MA. "Fine mapping of Wilms' tumors with 16q loss of heterozygosity localizes the putative tumor suppressor gene to a region of 6.7 megabases." Ann Surg Oncol 10.2 (March 2003): 136-143.
PMID
12620908
Source
pubmed
Published In
Annals of Surgical Oncology
Volume
10
Issue
2
Publish Date
2003
Start Page
136
End Page
143

Development of a novel tissue acquisition protocol for biomarker studies in early stage breast cancer.

Authors
Tebbit, CL; Ellis, M; Marks, JR; Bentley, RC; Mann, G; Soo, MS; Rosen, E; Baker, J; Leight, G; Olson, JA
MLA Citation
Tebbit, CL, Ellis, M, Marks, JR, Bentley, RC, Mann, G, Soo, MS, Rosen, E, Baker, J, Leight, G, and Olson, JA. "Development of a novel tissue acquisition protocol for biomarker studies in early stage breast cancer." 2003.
Source
wos-lite
Published In
Breast Cancer Research and Treatment
Volume
82
Publish Date
2003
Start Page
S143
End Page
S144

Does increased sectioning of ductal carcinoma in-situ (DCIS) pathologic specimens have clinical consequences?

Authors
Miller, KL; Marks, LB; Bentley, RC; Clough, RW; Prosnitz, RG; Leight, GS
MLA Citation
Miller, KL, Marks, LB, Bentley, RC, Clough, RW, Prosnitz, RG, and Leight, GS. "Does increased sectioning of ductal carcinoma in-situ (DCIS) pathologic specimens have clinical consequences?." December 2002.
Source
wos-lite
Published In
Breast Cancer Research and Treatment
Volume
76
Publish Date
2002
Start Page
S61
End Page
S61

Imaging-guided core needle biopsy of papillary lesions of the breast.

OBJECTIVE: Our objective was to assess the incidence of papillary lesions of the breast diagnosed at imaging-guided core needle biopsy and the need for surgical excision after a benign diagnosis. MATERIALS AND METHODS: This retrospective study included 1374 patients with consecutive suspicious breast lesions that underwent either mammography or sonographically guided large-core needle breast biopsy. Fifty-seven lesions (4%) were classified as papillary lesions. Eleven of the 57 cases were lost to follow-up (n = 6) or had not yet shown 2 years of stability (n = 5) and were excluded from this study. The remaining 46 papillary lesions constitute our study population. RESULTS: Surgical excision was performed in 17 (37%) of 46 papillary lesions. In the group of patients whose lesions were recommended for excision because carcinoma was identified at core biopsy, surgical excision revealed one false-positive and two true-positive diagnoses. In four cases, histologic diagnoses of the excisional biopsy and the core needle biopsy were discordant. One false-positive finding at core needle biopsy initially was interpreted as invasive ductal carcinoma on the basis of core needle biopsy specimens. In three false-negative findings, the initial diagnosis at core needle biopsy was upgraded after surgical excision. Two cases of papilloma with adjacent atypical ductal hyperplasia and one of atypical papilloma were upgraded to ductal carcinoma in situ after surgical excision. Imaging follow-up was performed in the remaining 29 patients. All lesions were stable or had decreased in size during the 2-year follow-up period. The negative predictive value of core needle biopsy for excluding malignancy among the papillary lesions diagnosed in our study was 93%. CONCLUSION: When the histologic diagnosis is benign, our data suggest that papillary lesions may be safely managed with imaging follow-up rather than with surgical excision. However, atypical papillary lesions or those associated with atypia require surgical excision because histologic underestimation occurs at a frequency similar to that in other atypical lesions undergoing core needle biopsy.

Authors
Rosen, EL; Bentley, RC; Baker, JA; Soo, MS
MLA Citation
Rosen, EL, Bentley, RC, Baker, JA, and Soo, MS. "Imaging-guided core needle biopsy of papillary lesions of the breast." AJR Am J Roentgenol 179.5 (November 2002): 1185-1192.
PMID
12388496
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
179
Issue
5
Publish Date
2002
Start Page
1185
End Page
1192
DOI
10.2214/ajr.179.5.1791185

Observations of tissue response to acoustic radiation force: opportunities for imaging.

Acoustic Radiation Force Impulse (ARFI) imaging is a method for characterizing local variations in tissue mechanical properties. In this method, a single ultrasonic transducer array is used to both apply temporally short localized radiation forces within tissue and to track the resulting displacements through time. In an ongoing study of the response of tissue to temporally short radiation force excitation, ARFI datasets have been obtained of ex vivo tissues under various focal configurations. The goal of this paper is to report observations of the response of tissue to radiation force and discuss the implications of these results in the construction of clinical imaging devices.

Authors
Nightingale, K; Bentley, R; Trahey, G
MLA Citation
Nightingale, K, Bentley, R, and Trahey, G. "Observations of tissue response to acoustic radiation force: opportunities for imaging." Ultrason Imaging 24.3 (July 2002): 129-138.
PMID
12503770
Source
pubmed
Published In
Ultrasonic Imaging
Volume
24
Issue
3
Publish Date
2002
Start Page
129
End Page
138
DOI
10.1177/016173460202400301

Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta.

BACKGROUND: Oral contraceptive (OC) use is associated with a reduced risk of ovarian cancer. An OC component, progestin, induces apoptosis in the primate ovarian epithelium. One regulator of apoptosis is transforming growth factor-beta (TGF-beta). We determined the effect of progestin on TGF-beta expression in the primate ovarian epithelium and examined the relationship between TGF-beta expression and apoptosis. METHODS: Female cynomolgus macaques were randomly assigned to receive a diet for 35 months containing no hormones (n = 20); the OC Triphasil (n = 17); or each of its constituents, ethinyl estradiol (estrogen, n = 20) or levonorgestrel (progestin, n = 18 ), alone. Ovarian sections were immunostained with monoclonal antibodies against TGF-beta1 or TGF-beta2 plus TGF-beta3 (TGF-beta2/3) isoforms. The expression of TGF-beta isoforms in four ovarian compartments (epithelium, oocytes, granulosa cells, and hilar vascular endothelium) was compared among treatment groups. The association between TGF-beta expression and apoptosis, as determined by morphology and histochemistry, was examined in ovarian epithelium. All statistical tests were two-sided. RESULTS: Compared with ovaries from the control and estrogen-only-treated monkeys, the ovaries of progestin-treated monkeys showed 1) a marked decrease in the expression of TGF-beta1 and a concomitant increase in the expression of the TGF-beta2/3 isoforms in the ovarian epithelium (P<.001), 2) an increase in the expression of TGF-beta2/3 in the hilar vascular endothelium (P<.001), and 3) a marked decrease in TGF-beta2/3 expression in granulosa cells (P<.001). The apoptotic index of the ovarian epithelium was highly associated with the change in expression from TGF-beta1 (P<.001) to TGF-beta2/3 (P

Authors
Rodriguez, GC; Nagarsheth, NP; Lee, KL; Bentley, RC; Walmer, DK; Cline, M; Whitaker, RS; Isner, P; Berchuck, A; Dodge, RK; Hughes, CL
MLA Citation
Rodriguez, GC, Nagarsheth, NP, Lee, KL, Bentley, RC, Walmer, DK, Cline, M, Whitaker, RS, Isner, P, Berchuck, A, Dodge, RK, and Hughes, CL. "Progestin-induced apoptosis in the Macaque ovarian epithelium: differential regulation of transforming growth factor-beta." J Natl Cancer Inst 94.1 (January 2, 2002): 50-60.
PMID
11773282
Source
pubmed
Published In
Journal of the National Cancer Institute
Volume
94
Issue
1
Publish Date
2002
Start Page
50
End Page
60

Acoustic radiation force impulse imaging: Remote palpation of the mechanical properties of tissue

An overview is given of the Acoustic Radiation Force Impulse (ARFI) imaging. It discusses the derivation of radiation force, the response of tissue to radiation force, and the potential for this imaging method to evaluate the mechanical properties of tissue. It is found that In vivo ARFI images of breast, abdomen, and carotid vessels demonstrate no speckle, good contrast between tissue structures, and resolution comparable to B-mode images.

Authors
Nightingale, K; Soo, MS; Nightingale, R; Bentley, R; Stutz, D; Palmeri, M; Dahl, J; Trahey, G
MLA Citation
Nightingale, K, Soo, MS, Nightingale, R, Bentley, R, Stutz, D, Palmeri, M, Dahl, J, and Trahey, G. "Acoustic radiation force impulse imaging: Remote palpation of the mechanical properties of tissue." Proceedings of the IEEE Ultrasonics Symposium 2 (2002): 1821-1830.
Source
scival
Published In
Proceedings of the IEEE Ultrasonics Symposium
Volume
2
Publish Date
2002
Start Page
1821
End Page
1830

CD34 expression in desmoplastic melanoma.

BACKGROUND: Primary and metastatic malignant melanoma can simulate various soft tissue tumors, including dermatofibrosarcoma protuberans (DFSP). Expression of CD34, a marker characteristic of DFSP, as well as other spindle cell tumors, has not been previously documented in malignant melanoma. METHODS: We present here an unusual case of metastatic malignant melanoma with a strong histologic resemblance to DFSP and also CD34 expression. RESULTS: The patient, a 72-year-old man with a history of an invasive malignant melanoma of the skin of the right lower abdomen, presented with a right axillary mass. Histologic sections revealed intersecting fascicles of spindle cells with nuclear pleomorphism and numerous mitotic figures, diffusely infiltrating the adipose tissue in a pattern closely simulating that seen in DFSP. In other foci, epithelioid neoplastic cells with abundant cytoplasm, prominent nucleoli, nuclear pseudoinclusions, and focal cytoplasmic melanin pigment were seen. The neoplastic spindle cells were strongly labeled by two anti-CD34 monoclonal antibodies. Some of the spindle cells and the majority of the epithelioid neoplastic cells expressed S-100 protein and focally tyrosinase. The tumor cells were negative for HMB-45 and MART-1. Melanosomes were not identified by electron microscopy. CONCLUSION: This case demonstrates the potential of melanoma to simulate DFSP closely, on both morphologic and immunohistochemical grounds, and confirms the utility of employing a broad panel of immunohistochemical reagents in problematic cases.

Authors
Hoang, MP; Selim, MA; Bentley, RC; Burchette, JL; Shea, CR
MLA Citation
Hoang, MP, Selim, MA, Bentley, RC, Burchette, JL, and Shea, CR. "CD34 expression in desmoplastic melanoma." J Cutan Pathol 28.10 (November 2001): 508-512.
PMID
11737519
Source
pubmed
Published In
Journal of Cutaneous Pathology
Volume
28
Issue
10
Publish Date
2001
Start Page
508
End Page
512

Mucolipidosis II (I-cell disease) presenting as neonatal cholestasis.

Authors
Hochman, JA; Treem, WR; Dougherty, F; Bentley, RC
MLA Citation
Hochman, JA, Treem, WR, Dougherty, F, and Bentley, RC. "Mucolipidosis II (I-cell disease) presenting as neonatal cholestasis." J Inherit Metab Dis 24.5 (October 2001): 603-604.
PMID
11757590
Source
pubmed
Published In
Journal of Inherited Metabolic Disease
Volume
24
Issue
5
Publish Date
2001
Start Page
603
End Page
604

Primary chondroid melanoma.

BACKGROUND: Malignant melanoma is notorious for the wide range of histologic patterns it can assume, among the least frequent of which is chondroid melamona. METHODS: Two cases of primary chondroid melanoma of the distal lower extremity were studied. Tissue for light microscopy was fixed in formalin, embedded in paraffin, and processed routinely. In one case, transmission electron microscopy and immunohistochemical evaluation were performed. RESULTS: Both cases exhibited melanoma in-situ, a conventional (non-chondroid) invasive component, and areas of chondroid differentiation, as confirmed by strongly positive staining with Alcian blue at pH 2.5 and Safranin O. Immunohistochemically, one case expressed S-100 protein and vimentin, and did not express gp100 (HMB-45), tyrosinase, MART-1, the Mel-5 antigen, the NKI/C3 antigen, CD45Ro, cytokeratin, or desmin. Electron microscopy of the chondroid component revealed occasional tumor cells with rare, membrane-bound, electron-dense organelles; the extracellular compartment showed amorphous ground substance consistent with cartilaginous differentiation. CONCLUSIONS: Chondroid change in the absence of osteogenic differentiation is extremely rare in malignant melanoma. Melanoma should be considered in the differential diagnosis of primary cutaneous neoplasms exhibiting cartilaginous differentiation.

Authors
Ackley, CD; Prieto, VG; Bentley, RC; Horenstein, MG; Seigler, HF; Shea, CR
MLA Citation
Ackley, CD, Prieto, VG, Bentley, RC, Horenstein, MG, Seigler, HF, and Shea, CR. "Primary chondroid melanoma." J Cutan Pathol 28.9 (October 2001): 482-485.
PMID
11553315
Source
pubmed
Published In
Journal of Cutaneous Pathology
Volume
28
Issue
9
Publish Date
2001
Start Page
482
End Page
485

Thrombospondin-1 expression in epithelial ovarian carcinoma: association with p53 status, tumor angiogenesis, and survival in platinum-treated patients.

OBJECTIVE: The regulation of the metastatic process in epithelial ovarian cancer has not been well defined. Similar to other tumor types, the angiogenic phenotype in ovarian cancer strongly influences clinical outcome, suggesting that the acquisition of a pro-angiogenic environment is essential to the process of ovarian cancer proliferation and metastasis. Thrombospondin-1 (TSP-1) is a potent peptide shown in other tumor systems to be associated with angiogenesis and possibly regulated by p53, a gene which is mutated in as high as 50% of advanced ovarian cancers. The purpose of this study was to investigate TSP-1 expression in invasive epithelial ovarian cancer and to examine the relationship between TSP-1 expression and the degree of angiogenesis. In addition, we examined whether TSP-1 expression was associated with overexpression of p53. METHODS: Frozen sections obtained from 85 patients with invasive epithelial ovarian cancer were examined immunohistochemically for expression of TSP-1 and p53. The sections were examined microscopically by two investigators, who were blinded to the clinicopathologic variables. Outcome variables included the correlation among TSP-1, angiogenesis, and p53, as well as the association between TSP-1 expression and survival. RESULTS: The majority (62%) of cases demonstrated high levels (3+) of TSP-1 expression; 7% demonstrated no TSP-1 expression. p53 was overexpressed in 55% of cases, and expression was inversely correlated with TSP-1 staining. Thirteen cancers had 0 or 1+ TSP-1 staining; 12 (92%) of these overexpressed the p53 protein. In contrast, only 49% of tumors with high expression of TSP-1 have overexpression of p53 (P = 0.02). TSP-1 was suggestive for improved survival in patients with advanced disease; high TSP-1 expression was associated with a median survival of 2.4 years compared to 1.5 years for patients with tumors having a lower degree of TSP-1 expression (P = 0.06). CONCLUSION: These data suggest that TSP-1 may possess a tumor inhibitory function in patients with advanced epithelial ovarian carcinoma. The reduction of TSP-1 expression associated with overexpression of p53 may be coupled with the development of a pro-angiogenic environment and malignant phenotype.

Authors
Alvarez, AA; Axelrod, JR; Whitaker, RS; Isner, PD; Bentley, RC; Dodge, RK; Rodriguez, GC
MLA Citation
Alvarez, AA, Axelrod, JR, Whitaker, RS, Isner, PD, Bentley, RC, Dodge, RK, and Rodriguez, GC. "Thrombospondin-1 expression in epithelial ovarian carcinoma: association with p53 status, tumor angiogenesis, and survival in platinum-treated patients." Gynecologic oncology 82.2 (August 2001): 273-278.
PMID
11531279
Source
epmc
Published In
Gynecologic Oncology
Volume
82
Issue
2
Publish Date
2001
Start Page
273
End Page
278
DOI
10.1006/gyno.2001.6287

Impact of core-needle breast biopsy on the surgical management of mammographic abnormalities.

OBJECTIVE: To evaluate the accuracy of percutaneous, image-guided core-needle breast biopsy (CNBx) and to compare the surgical management of patients with breast cancer diagnosed by CNBx with patients diagnosed by surgical needle-localization biopsy (SNLBx). SUMMARY BACKGROUND DATA: Percutaneous, image-guided CNBx is a less invasive alternative to SNLBx for the diagnosis of nonpalpable mammographic abnormalities. CNBx potentially spares patients with benign lesions from unnecessary surgery, although false-negative results can occur. For patients with malignant lesions, preoperative diagnosis by CNBx allows definitive treatment decisions to be made before surgery and may affect surgical outcomes. METHODS: Between 1992 and 1999, 939 patients with 1,042 mammographically detected lesions underwent biopsy by stereotactic CNBx or ultrasound-guided CNBx. Results were categorized pathologically as benign or malignant and, further, as invasive or noninvasive malignancies. Only biopsy results confirmed by excision or 1-year-minimum mammographic follow-up were included in the analysis. Patients with breast cancer diagnosed by CNBx were compared with a matched control group of patients with breast cancer diagnosed by SNLBx. RESULTS: Benign results were obtained in 802 lesions (77%), 520 of which were in patients with adequate follow-up. Ninety-five of the 520 evaluable lesions (18%) were subsequently excised because of atypical hyperplasia, mammographic-histologic discordance, or other clinical indications. There were 17 false-negative CNBx results in this group; 15 of these lesions were correctly diagnosed by excisional biopsy within 4 months of CNBx. In two patients (0.9%), delayed diagnoses of ductal carcinoma in situ were made at 15 and 19 months after CNBx. Malignant results were obtained in 240 lesions (23%), 220 of which were surgically excised from 202 patients at our institution. Two lesions diagnosed as ductal carcinoma in situ were reclassified as atypical ductal hyperplasia and considered false-positive results (0.4%). For malignant lesions, the sensitivity and specificity of CNBx for the detection of invasion were 89% and 96%, respectively. During the first surgical procedure, 115 of 199 patients (58%) diagnosed by CNBx underwent local excision; 194 of 199 patients (97%) evaluated by SNLBx underwent local excision. For patients whose initial surgery was local excision, those diagnosed before surgery by CNBx had larger excision specimens and were more likely to have negative surgical margins than were patients initially evaluated by SNLBx. Overall, patients diagnosed by CNBx required fewer surgical procedures for definitive treatment than did patients diagnosed by SNLBx. CONCLUSIONS: Diagnosis by CNBx spares most patients with benign mammographic abnormalities from unnecessary surgery. With the selective use of SNLBx to confirm discordant results, missed diagnoses are rare. When compared with SNLBx, preoperative diagnosis of breast cancer by CNBx facilitates wider initial margins of excision, fewer positive margins, and fewer surgical procedures to accomplish definitive treatment than diagnosis by SNLBx.

Authors
White, RR; Halperin, TJ; Olson, JA; Soo, MS; Bentley, RC; Seigler, HF
MLA Citation
White, RR, Halperin, TJ, Olson, JA, Soo, MS, Bentley, RC, and Seigler, HF. "Impact of core-needle breast biopsy on the surgical management of mammographic abnormalities." Ann Surg 233.6 (June 2001): 769-777.
PMID
11371735
Source
pubmed
Published In
Annals of Surgery
Volume
233
Issue
6
Publish Date
2001
Start Page
769
End Page
777

Synergism between platelets and leukocytes in inducing endothelial cell apoptosis in the cold ischemic rat liver: a Kupffer cell-mediated injury.

Authors
Sindram, D; Porte, RJ; Hoffman, MR; Bentley, RC; Clavien, PA
MLA Citation
Sindram, D, Porte, RJ, Hoffman, MR, Bentley, RC, and Clavien, PA. "Synergism between platelets and leukocytes in inducing endothelial cell apoptosis in the cold ischemic rat liver: a Kupffer cell-mediated injury." FASEB J 15.7 (May 2001): 1230-1232.
PMID
11344097
Source
pubmed
Published In
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume
15
Issue
7
Publish Date
2001
Start Page
1230
End Page
1232

Malignancy in endometriosis: frequency and comparison of ovarian and extraovarian types.

One thousand consecutive cases of surgically proven endometriosis were reviewed to evaluate the frequency and types of pelvic cancers that were associated with ovarian and extraovarian endometriosis. The frequency and types of histologic abnormalities present in the eutopic endometrium when cancers were noted in endometriosis were also evaluated. In the large subset of cases for which the authors were the primary pathologists and all foci of endometriosis were recorded, the frequency of malignancy was 10.8%. In contrast, the frequency was only 3.2% in cases diagnosed by others previously in our institution. Cancers were more commonly found in ovaries when endometriosis was present in that ovary (5%) compared to when endometriosis was present at other sites (1%). Clear cell and endometrioid carcinomas were the malignancies most commonly seen in ovaries containing endometriosis, while clear cell adenocarcinoma and adenosarcoma were most commonly seen in conjunction with extraovarian endometriosis. The association of endometriosis with endometrioid and clear cell carcinoma was much stronger than that of serous and mucinous tumors (p < .01). Concurrent endometrial pathology was commonly seen in cases of malignant transformation of endometriosis (32% of cases).

Authors
Stern, RC; Dash, R; Bentley, RC; Snyder, MJ; Haney, AF; Robboy, SJ
MLA Citation
Stern, RC, Dash, R, Bentley, RC, Snyder, MJ, Haney, AF, and Robboy, SJ. "Malignancy in endometriosis: frequency and comparison of ovarian and extraovarian types." Int J Gynecol Pathol 20.2 (April 2001): 133-139.
PMID
11293158
Source
pubmed
Published In
International Journal of Gynecological Pathology
Volume
20
Issue
2
Publish Date
2001
Start Page
133
End Page
139

Comparison of methods of measuring HER-2 in metastatic breast cancer patients treated with high-dose chemotherapy.

PURPOSE: HER-2 is overexpressed in 20% to 30% of human breast cancer and is associated with poor outcome. Studies suggest an association between HER-2 overexpression and resistance to alkylating agents. To further evaluate this relationship, we assessed the interaction of HER-2, measured by different methods, and outcome after dose intensification with alkylating agents in metastatic breast cancer. PATIENTS AND METHODS: From 1988 to 1995 at Duke University, 425 patients with metastatic breast cancer were enrolled in a study of high-dose alkylating agents (HDC) with autologous cellular support after doxorubicin-based therapy (AFM). HER-2 was measured in serum for shed extracellular domain (ECD) and in tissue by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). RESULTS: HER-2 ECD was positive in 29% (19 of 65) of patients pre-AFM and in 11.7% (34 of 290) pre-HDC. Higher pre-AFM and higher pre-HDC HER-2 ECD predicted worse overall survival (P =.045 and P =.0096, respectively). HER-2 overexpression by IHC and FISH showed no correlation with worse disease-free survival or overall survival. FISH and ECD were highly specific for IHC (97.3% and 97.7% respectively). However, ECD had a low sensitivity for IHC-only 22% of patients with HER-2 in the primary tumor shed ECD into the serum. CONCLUSION: These data suggest that the method of measuring HER-2 is important in predicting clinical outcome. HER2 ECD may identify a poor prognosis subgroup of HER-2-positive tumors. Lack of association of HER2 by IHC/FISH with worse outcome suggests that therapy with AFM and/or HDC therapy may be able to overcome the effect of this prognostic factor or it may not be a prognostic factor in this setting.

Authors
Harris, LN; Liotcheva, V; Broadwater, G; Ramirez, MJ; Maimonis, P; Anderson, S; Everett, T; Harpole, D; Moore, MB; Berry, DA; Rizzeri, D; Vredenburgh, JJ; Bentley, RC
MLA Citation
Harris, LN, Liotcheva, V, Broadwater, G, Ramirez, MJ, Maimonis, P, Anderson, S, Everett, T, Harpole, D, Moore, MB, Berry, DA, Rizzeri, D, Vredenburgh, JJ, and Bentley, RC. "Comparison of methods of measuring HER-2 in metastatic breast cancer patients treated with high-dose chemotherapy." J Clin Oncol 19.6 (March 15, 2001): 1698-1706.
PMID
11250999
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
19
Issue
6
Publish Date
2001
Start Page
1698
End Page
1706
DOI
10.1200/JCO.2001.19.6.1698

K-ras mutations in Müllerian inclusion cysts associated with serous borderline tumors of the ovary.

OBJECTIVE: Müllerian inclusion cysts (MIC) are small benign appearing glands that are occasionally noted in lymph nodes and peritoneal biopsies. They occur most frequently in women with serous ovarian tumors, with borderline tumors (SBOT) having a higher incidence than invasive cancers. The aim of this study was to examine whether MIC and SBOT have identical K-ras mutations, which would suggest that they are related. Methods. Six patients in whom adequate tissue was available from SBOT, MIC, and normal tissue were identified from a consecutive series of patients with SBOT who underwent lymph node sampling from 1992 to 1997 at Duke University Medical Center. DNA extraction was performed using laser capture microdissection. Exon 1 of the K-ras gene was amplified using PCR and subjected to single-strand conformation analysis to screen for mutations. Shifted bands were sequenced to confirm the presence of mutations. RESULTS: Mutations in codon 12 of K-ras were found in three of six (50%) SBOT. In two of these three cases, the identical mutation was found in the SBOT and the MIC (gly to val in both cases), but not in the corresponding normal DNA. In one case, a mutation was seen in the ovarian tumor (gly to asp), but not in the corresponding MIC. CONCLUSIONS: Mutations in codon 12 of the K-ras gene are a hallmark of serous borderline tumors. The presence of identical K-ras mutations in some SBOT and their associated MIC suggests that they are related processes. Both may arise due to a field effect, or alternatively some MIC may represent metastases from the primary ovarian tumor.

Authors
Alvarez, AA; Moore, WF; Robboy, SJ; Bentley, RC; Gumbs, C; Futreal, PA; Berchuck, A
MLA Citation
Alvarez, AA, Moore, WF, Robboy, SJ, Bentley, RC, Gumbs, C, Futreal, PA, and Berchuck, A. "K-ras mutations in Müllerian inclusion cysts associated with serous borderline tumors of the ovary." Gynecol Oncol 80.2 (February 2001): 201-206.
PMID
11161860
Source
pubmed
Published In
Gynecologic Oncology
Volume
80
Issue
2
Publish Date
2001
Start Page
201
End Page
206
DOI
10.1006/gyno.2000.6066

Pathologic quiz case: pituitary mass in a 48-year-old woman.

Authors
Cummings, TJ; Bentley, RC; McLendon, RE
MLA Citation
Cummings, TJ, Bentley, RC, and McLendon, RE. "Pathologic quiz case: pituitary mass in a 48-year-old woman." Arch Pathol Lab Med 125.2 (February 2001): 299-300.
PMID
11175658
Source
pubmed
Published In
Archives of Pathology and Laboratory Medicine
Volume
125
Issue
2
Publish Date
2001
Start Page
299
End Page
300
DOI
10.1043/0003-9985(2001)125<0299:PQCPMI>2.0.CO;2

Pathologic quiz case - Pituitary mass in a 48-year-old woman - Pathologic diagnosis: Granular cell tumor of the infundibulum

Authors
Cummings, TJ; Bentley, RC; McLendon, RE
MLA Citation
Cummings, TJ, Bentley, RC, and McLendon, RE. "Pathologic quiz case - Pituitary mass in a 48-year-old woman - Pathologic diagnosis: Granular cell tumor of the infundibulum." ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE 125.2 (February 2001): 299-300.
Source
wos-lite
Published In
Archives of Pathology and Laboratory Medicine
Volume
125
Issue
2
Publish Date
2001
Start Page
299
End Page
300

Mammographic-pathologic correlation: Part 2. Malignant breast lesions

The primary goal of the radiologist in interpreting mammograms is to detect abnormalities that are suggestive of malignancy. Unfortunately, great deal of overlap exists between the imaging patterns produced by benign and malignant breast lesions, creating the possibility of both false-positive and false-negative results. In the first part of this series, we discussed the mammographic appearance of a number of common benign entities along with several lesions that are most easily confused with carcinoma. In this article, we present the relevant clinical, imaging, and pathologic features of malignant diseases of the breast. We will focus our discussion on primary adenocarcinomas of the breast. Neoplasms arising from tissues other than breast epithelium (e.g., sarcomas, lymphomas), metastatic disease to the breast, and phyllodes tumors will not be included.

Authors
Kornguth, PJ; Bentley, RC
MLA Citation
Kornguth, PJ, and Bentley, RC. "Mammographic-pathologic correlation: Part 2. Malignant breast lesions." Journal of Women's Imaging 3.4 (2001): 134-145.
Source
scival
Published In
Journal of Women's Imaging
Volume
3
Issue
4
Publish Date
2001
Start Page
134
End Page
145
DOI
10.1097/00130747-200111000-00005

In vivo demonstration of acoustic radiation force impulse (ARFI) imaging in the thyroid, abdomen, and breast

Acoustic Radiation Force Impulse (ARFI) imaging is proposed as a method for characterizing local variations in tissue mechanical response. In this method, a single ultrasonic transducer array is used to both apply localized radiation forces within tissue and to track the resulting displacements. Tissue displacement is inversely proportional to tissue stiffness, and the temporal response of tissue to radiation force varies with tissue type. We have previously presented results generated using radiation force applied in a single pushing location in vivo, and using multiple pushing locations in tissue phantoms where the data was acquired over several minutes. In this paper, data are presented that were acquired using multiple applications of radiation force to interrogate an extended region of interest in a real-time data acquisition implementation, using beam sequences similar to those used for Color Doppler. In vivo ARFI images of the thyroid, abdomen, and breast are presented. Peak displacements of 5, 10, and 8 microns were observed in the these tissues, respectively. In all cases, the ARFI images and matched B-mode images show highly correlated structural information, and comparable resolution. Images of the thyroid exhibit remarkable uniformity in displacement with no speckle. The results suggest considerable clinical potential for ARFI imaging.

Authors
Nightingale, K; Soo, MS; Nightingale, R; Bentley, R; Trahey, G
MLA Citation
Nightingale, K, Soo, MS, Nightingale, R, Bentley, R, and Trahey, G. "In vivo demonstration of acoustic radiation force impulse (ARFI) imaging in the thyroid, abdomen, and breast." Proceedings of the IEEE Ultrasonics Symposium 2 (2001): 1633-1638.
Source
scival
Published In
Proceedings of the IEEE Ultrasonics Symposium
Volume
2
Publish Date
2001
Start Page
1633
End Page
1638

Mammographic-pathologic correlation: Part 1. Benign breast lesions

A great deal of overlap exists in the mammographic appearance of benign and malignant breast lesions. This makes the radiologist's job more difficult and results in a substantial false-positive rate. Thorough knowledge of the clinical presentation, mammographic appearance, and histopathology of benign breast entities is essential to lowering one's false-positive rate. This article covers some of the most common benign breast lesions (those that can be categorized as benign or probably benign at the end of the imaging workup) and those that can be easily confused with carcinoma.

Authors
Kornguth, PJ; Bentley, RC
MLA Citation
Kornguth, PJ, and Bentley, RC. "Mammographic-pathologic correlation: Part 1. Benign breast lesions." Journal of Women's Imaging 3.1 (2001): 29-37.
Source
scival
Published In
Journal of Women's Imaging
Volume
3
Issue
1
Publish Date
2001
Start Page
29
End Page
37

Pathology and pathophysiology of uterine smooth-muscle tumors.

Smooth-muscle tumors of uterine origin encompass a broad family of neoplasms. The leiomyoma, by far the most common of all the neoplasms, generally is hormone sensitive, with rates of growth semiquantitatively related to estrogen and progesterone receptor levels. Several forms of degenerative change can occur in the leiomyoma. The most common is hyaline degeneration, which is important in that it should not be mistaken for the coagulative tumor cell necrosis seen in leiomyosarcoma. Red degeneration (necrobiosis) is a form of degeneration that occurs characteristically but not exclusively in pregnancy, and the process is often the cause of pain and fever. Several forms of treatment have been used medically in the treatment of leiomyoma. Gonadotropin-releasing hormone analogs or agonists or selective arterial embolization with polyvinylformaldehyde particles may lead to substantial degeneration or infarction of the leiomyoma, respectively. Several variants of leiomyoma, the cellular and symplastic leiomyomas, are important to recognize, as they can be misinterpreted as sarcoma. In addition, there are two unusual growth patterns of leiomyoma that are important to recognize. Both the benign metastasizing leiomyoma and disseminated peritoneal leiomyomatosis are found outside the uterus, and neither is malignant. Recent studies offer insights into their origin and hormonal influences. From a diagnostic and therapeutic point of view, the leiomyosarcoma, while rare, is clinically of great import. Coagulative necrosis, cytologic atypia, and mitotic counts are all important in diagnosing the condition.

Authors
Robboy, SJ; Bentley, RC; Butnor, K; Anderson, MC
MLA Citation
Robboy, SJ, Bentley, RC, Butnor, K, and Anderson, MC. "Pathology and pathophysiology of uterine smooth-muscle tumors." Environ Health Perspect 108 Suppl 5 (October 2000): 779-784. (Review)
PMID
11035982
Source
pubmed
Published In
Environmental health perspectives
Volume
108 Suppl 5
Publish Date
2000
Start Page
779
End Page
784

Kupffer cells mediate leukocyte and platelet synergism causing sinusoidal endothelial cell apoptosis of the cold ischemic rat liver

Authors
Sindram, D; Porte, RJ; Bentley, RC; Clavien, PA
MLA Citation
Sindram, D, Porte, RJ, Bentley, RC, and Clavien, PA. "Kupffer cells mediate leukocyte and platelet synergism causing sinusoidal endothelial cell apoptosis of the cold ischemic rat liver." HEPATOLOGY 32.4 (October 2000): 208A-208A.
Source
wos-lite
Published In
Hepatology
Volume
32
Issue
4
Publish Date
2000
Start Page
208A
End Page
208A

Human chorionic gonadotropin beta subunit protein immunoreactivity in pituitary adenomas: Pathologic features

Authors
Cummings, TJ; McLendon, RE; Villavicencio, AT; Friedman, AH; Burchette, JL; Bentley, RC
MLA Citation
Cummings, TJ, McLendon, RE, Villavicencio, AT, Friedman, AH, Burchette, JL, and Bentley, RC. "Human chorionic gonadotropin beta subunit protein immunoreactivity in pituitary adenomas: Pathologic features." BRAIN PATHOLOGY 10.4 (September 2000): 746-747.
Source
wos-lite
Published In
Brain Pathology
Volume
10
Issue
4
Publish Date
2000
Start Page
746
End Page
747

Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans.

OBJECTIVE: To determine whether ischemic preconditioning protects the human liver against a subsequent period of ischemia in patients undergoing hemihepatectomy, and to identify possible underlying protective mechanisms of ischemic preconditioning, such as inhibition of hepatocellular apoptosis. SUMMARY BACKGROUND DATA: Ischemic preconditioning is a short period of ischemia followed by a brief period of reperfusion before a sustained ischemic insult. Recent studies in rodents suggest that ischemic preconditioning is a simple and powerful protective modality against ischemic injury of the liver. The underlying mechanisms are thought to be related to downregulation of the apoptotic pathway. METHODS: Twenty-four patients undergoing hemihepatectomy for various reasons alternatively received ischemic preconditioning (10 minutes of ischemia and 10 minutes of reperfusion) before transection of the liver performed under inflow occlusion for exactly 30 minutes. Liver wedge and Tru-cut biopsy samples were obtained at the opening of the abdomen and 30 minutes after the end of the hepatectomy. Serum levels of aspartate transferase, alanine transferase, bilirubin and prothrombin time were determined daily until discharge. Hepatocellular apoptosis was evaluated by in situ terminal deoxynucleotidyl transferase mediated d-UTP nick end-labeling (TUNEL) assay and electron microscopy. Caspase 3 and 8 activities were measured in tissue using specific fluorometric assays. RESULTS: Serum levels of aspartate transferase and alanine transferase were reduced by more than twofold in patients subjected to ischemic preconditioning versus controls. The analysis of a subgroup of patients with mild to moderate steatosis indicated possible increased protective effects of ischemic preconditioning. In situ TUNEL staining demonstrated a dramatic reduction in the number of apoptotic sinusoidal lining cells in the ischemic preconditioning group. Electron microscopy confirmed features of apoptosis present in control but not in ischemic preconditioning patients. There was no significant difference in caspase 3 and 8 activity when patients with ischemic preconditioning were compared with controls. CONCLUSIONS: Ischemic preconditioning is a simple and effective modality protecting the liver against subsequent prolonged periods of ischemia. This strategy may be a more attractive technique than intermittent inflow occlusion, which is associated with increased blood loss during each period of reperfusion.

Authors
Clavien, PA; Yadav, S; Sindram, D; Bentley, RC
MLA Citation
Clavien, PA, Yadav, S, Sindram, D, and Bentley, RC. "Protective effects of ischemic preconditioning for liver resection performed under inflow occlusion in humans." Ann Surg 232.2 (August 2000): 155-162.
PMID
10903590
Source
pubmed
Published In
Annals of Surgery
Volume
232
Issue
2
Publish Date
2000
Start Page
155
End Page
162

Bilateral pelvic lymph node metastases in a case of FIGO stage IA(1) adenocarcinoma of the cervix.

INTRODUCTION: Although the FIGO staging system has been recently described for microinvasive adenocarcinoma of the cervix, the precise role it will have on determining how patients are treated remains uncertain. Using various definitions for the classification of microinvasion, recent reports have suggested conservative management for patients with this disease. CASE: We present the case of a 62-year-old woman with FIGO stage IA(1) adenocarcinoma of the cervix found to have bilateral microscopic pelvic lymph node metastases. To our knowledge, this is the only documented case of lymph node metastases in a patient with IA(1) disease. CONCLUSIONS: A review of the controversial issues involving the definition and management of microinvasive adenocarcinoma of the cervix is presented. The finding of lymph node metastases in our patient provides support for aggressive surgical management in selected patients with this disease.

Authors
Nagarsheth, NP; Maxwell, GL; Bentley, RC; Rodriguez, G
MLA Citation
Nagarsheth, NP, Maxwell, GL, Bentley, RC, and Rodriguez, G. "Bilateral pelvic lymph node metastases in a case of FIGO stage IA(1) adenocarcinoma of the cervix." Gynecol Oncol 77.3 (June 2000): 467-470.
PMID
10831362
Source
pubmed
Published In
Gynecologic Oncology
Volume
77
Issue
3
Publish Date
2000
Start Page
467
End Page
470
DOI
10.1006/gyno.2000.5786

Some mullerian inclusion cysts in lymph nodes may sometimes be metastases from serous borderline tumors of the ovary.

Glandular inclusions that appear morphologically benign are occasionally found in lymph nodes as well as in peritoneal and omental biopsies. In patients with gynecologic malignancies, the nature and significance of these mullerian inclusion cysts (MIC) present a diagnostic challenge with regard to whether they are benign and incidental or are related to the coincident tumor for which surgery is being performed. Sixty-two cases of MIC were prospectively identified during a 6-year period. The frequencies were calculated and stratified by lymph node chain distribution, primary tumor site, and primary tumor type. MIC appeared as small cysts lined by a serous (mullerian)-type, cytologically bland, cuboidal to columnar epithelium with a simple architecture. Among 62 women, MIC was found in lymph nodes (27 cases), pelvic peritoneum (19 cases), omentum (16 cases), bowel serosa (9 cases), uterine serosa (8 cases), and parametrial connective tissues (4 cases). Among a set of 417 consecutive cases in which lymphadenectomy was performed, 46 (11%) women had MIC. The MIC involved multiple sites (26 cases in the peritoneum/omentum and 27 in lymph nodes). The primary tumor was in the ovary in 32 of the 46 women with MIC (70%) and of these, 17 were borderline serous (53%). Sixty-two of 6,154 lymph nodes examined contained MIC (1.0%). 3.2% of nodes contained MIC in which the primary tumor arose in the ovary, but only 0.1% with either endometrial or cervical tumors (chi2, p <0.00001). The lymph nodes most often involved by MIC were from para-aortic sites (40%), which reflect the primary drainage route from the ovary. Not uncommonly, neighboring areas in the same lymph node group with MIC disclosed separate foci of obvious metastatic borderline tumor (4 of 10; 40%). In summary, the increased frequency of MIC in lymph nodes sampled for primary ovarian malignancies suggests that MIC in some cases, rather than being benign, incidental inclusions, are more likely bland-appearing forms of metastatic tumor. The preponderance of inclusions occurs with serous ovarian tumors of borderline malignancy, and the inclusions are overrepresented in the lymph nodes that primarily receive drainage from the ovary.

Authors
Moore, WF; Bentley, RC; Berchuck, A; Robboy, SJ
MLA Citation
Moore, WF, Bentley, RC, Berchuck, A, and Robboy, SJ. "Some mullerian inclusion cysts in lymph nodes may sometimes be metastases from serous borderline tumors of the ovary." Am J Surg Pathol 24.5 (May 2000): 710-718.
PMID
10800990
Source
pubmed
Published In
American Journal of Surgical Pathology
Volume
24
Issue
5
Publish Date
2000
Start Page
710
End Page
718

The outcome of stage I-II clinically and surgically staged papillary serous and clear cell endometrial cancers when compared with endometrioid carcinoma.

PURPOSE: The aim of this study was to compare survival and recurrence in clinical and surgical stage I-II papillary serous (PS), clear cell (CC), and endometrioid (EM) cancers of the endometrium and examine the prognostic utility of myometrial invasion. METHODS: Clinical, surgicopathologic, and survival data were retrospectively collected on 574 clinical stage I-II endometrial cancer patients, including 53 PS and 18 CC (based on postoperative histology), undergoing hysterectomy at Duke University Medical Center between 1967 and 1990. All staging material was available and reexamined prior to this analysis, and FIGO surgical staging was retrospectively assigned. Prognostic variables examined included age, stage, grade, myometrial invasion, lymph-vascular space invasion (LVSI), and histology. PS and CC histologic subtypes were compared as both common category and discrete categories versus EM, EM grade 1 (EM1), EM grade 2 (EM2), and EM grade 3 (EM3). Statistical analyses were performed using chi(2), Fisher's exact, and Wilcoxon rank sum tests, Cox regression analysis, and Kaplan-Meier survival analysis. RESULTS: PS tumors accounted for 9%, CC for 3%, and EM for 88% of cases. Recurrences were more frequent among PS (38%) and CC (22%) compared with EM (9%) (P < 0.001 and 0.08, respectively), and PS recurred more frequently than EM3 alone (20%) (P = 0.06). Among PS, CC, and EM3 patients with recurrences there were no statistical differences in the proportion that received preoperative or postoperative radiotherapy or chemotherapy. Prognostic factors for shorter survival included age >=60, surgical stage III+IV, presence of LVSI, histology (PS, CC, or EM3), and >=50% myometrial invasion. The estimated 5-year survival of PS+CC patients with <2 mm myometrial invasion is 0.56 compared to 0.93 for EM patients (P < 0. 001). PS + CC tumors confined to the endometrium had a 5-year survival of 0.60 compared to 0.98 and 1.00 for EM and EM3, respectively. The 5-year survival for surgically staged IA patients (0.57) was not different from stages IB and IC combined (0.53) (P = 0.72). The 5-year survival for surgical stage I + II PS + CC patients (0.56) was comparable to that for clinical stage I + II PS + CC patients (0.46) and remained significantly smaller than that for EM patients (0.86) (P < 0.001). CONCLUSION: Recurrences are more frequent among PS and CC tumors compared with EM and among PS compared with EM3. When controlled for surgical stage I-II tumors, 5-year survival for PS + CC patients remains comparable to that of clinical stage I-II patients and below that of EM. Prognostic factors for survival in PS and CC patients include age, stage, and LVSI. PS, CC, and EM3 subtypes together are predictors of poor survival. Thorough extended surgical staging is indicated in PS and CC tumors, and prospective trials of aggressive adjuvant therapies for surgical stage I-II tumors are needed to improve outcome in PS and CC patients.

Authors
Cirisano, FD; Robboy, SJ; Dodge, RK; Bentley, RC; Krigman, HR; Synan, IS; Soper, JT; Clarke-Pearson, DL
MLA Citation
Cirisano, FD, Robboy, SJ, Dodge, RK, Bentley, RC, Krigman, HR, Synan, IS, Soper, JT, and Clarke-Pearson, DL. "The outcome of stage I-II clinically and surgically staged papillary serous and clear cell endometrial cancers when compared with endometrioid carcinoma." Gynecol Oncol 77.1 (April 2000): 55-65.
PMID
10739691
Source
pubmed
Published In
Gynecologic Oncology
Volume
77
Issue
1
Publish Date
2000
Start Page
55
End Page
65
DOI
10.1006/gyno.2000.5737

Tubular adenomas of the breast: imaging findings with histologic correlation.

OBJECTIVE: The purpose of this study is to describe the imaging features of tubular adenomas, which are rare benign breast tumors usually found in women younger than 35 years old. CONCLUSION: In young women, tubular adenomas can look like noncalcified fibroadenomas on mammography and sonography. In older women, tubular adenomas may resemble malignant masses with microcalcifications. Awareness of these findings may help in assessing concordance between imaging and histologic findings after percutaneous core biopsy of these rare lesions.

Authors
Soo, MS; Dash, N; Bentley, R; Lee, LH; Nathan, G
MLA Citation
Soo, MS, Dash, N, Bentley, R, Lee, LH, and Nathan, G. "Tubular adenomas of the breast: imaging findings with histologic correlation." AJR Am J Roentgenol 174.3 (March 2000): 757-761.
PMID
10701621
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
174
Issue
3
Publish Date
2000
Start Page
757
End Page
761
DOI
10.2214/ajr.174.3.1740757

Platelets induce sinusoidal endothelial cell apoptosis upon reperfusion of the cold ischemic rat liver.

BACKGROUND & AIMS: Sinusoidal endothelial cell (SEC) apoptosis is a central feature of reperfusion injury in liver transplantation. Platelet sequestration occurs after transplantation with possible deleterious effects. We tested the hypothesis that platelets mediate SEC apoptosis. METHODS: Livers were perfused after 24 hours of cold preservation in University of Wisconsin solution in an isolated perfused rat liver model. The perfusate contained isolated syngeneic red blood cells and purified platelets. Effects of inhibiting platelet adhesion on SEC apoptosis was tested using sialyl Lewis-X oligosaccharide (sLe(x)), a natural ligand of selectin adhesion molecules. Reperfusion injury was assessed by established markers of injury. Apoptosis was determined by TUNEL and electron microscopy. RESULTS: A third of the circulating platelets was rapidly sequestered in the liver after reperfusion. This was associated with increased graft injury. Single platelets were adherent to sinusoidal lining without morphological or dynamic evidence of impairment of microcirculation. TUNEL staining revealed a 6-fold increase in the number of apoptotic SECs at 1 hour of reperfusion. No hepatocyte death or evidence of necrosis was detected up to 3 hours of reperfusion. Addition of sLe(x) inhibited adhesion and significantly reduced SEC apoptosis. CONCLUSIONS: Platelets cause SEC apoptosis upon reperfusion of liver grafts. Prevention of adhesion is protective.

Authors
Sindram, D; Porte, RJ; Hoffman, MR; Bentley, RC; Clavien, PA
MLA Citation
Sindram, D, Porte, RJ, Hoffman, MR, Bentley, RC, and Clavien, PA. "Platelets induce sinusoidal endothelial cell apoptosis upon reperfusion of the cold ischemic rat liver." Gastroenterology 118.1 (January 2000): 183-191.
PMID
10611167
Source
pubmed
Published In
Gastroenterology
Volume
118
Issue
1
Publish Date
2000
Start Page
183
End Page
191

Focal fibrosis: a common breast lesion diagnosed at imaging-guided core biopsy.

OBJECTIVE: Focal fibrosis is a benign breast lesion commonly diagnosed by imaging-guided core biopsy. The goal of this study is to determine the frequency of focal fibrosis diagnosed at core biopsy and to describe its imaging features. MATERIALS AND METHODS: A consecutive series of 894 imaging-guided breast core biopsies were reviewed, and all cases of focal fibrosis were selected. The imaging features of each lesion were characterized. All lesions had been reviewed during radiologic-histologic review sessions to assess for accurate needle positioning and concordant results. Follow-up imaging and histologic data were reviewed to document lesion stability. RESULTS: Focal fibrosis was diagnosed in 80 (8.9%) of 894 imaging-guided core biopsies: 20 (8.7%) of 229 sonographically guided biopsies and 60 (9.0%) of 665 mammographically guided biopsies. Of 75 mammographically visible lesions, 39 (52%) were masses, 29 (39%) were densities, and seven (9.3%) were clusters of calcifications. Thirty-five hypoechoic lesions were visualized on sonography: 29 (80%) were oval, and six (17%) were irregularly shaped. Six (21%) of the 28 oval masses showed posterior enhancement, four (14%) posterior shadowing, and 19 (68%) neither feature. Fifty-two (65%) of 80 patients with focal fibrosis had routine imaging follow-up; all had stable findings (mean follow-up period, 27 months). No false-negative cases were identified. CONCLUSION: Focal fibrosis most commonly appears as an enlarging solid mass or developing density on mammography or as an oval mass on sonography. Our data suggest that focal fibrosis accounts for 9% of lesions that undergo imaging-guided core biopsy and that the diagnosis can be accurately reached using imaging-guided biopsy.

Authors
Rosen, EL; Soo, MS; Bentley, RC
MLA Citation
Rosen, EL, Soo, MS, and Bentley, RC. "Focal fibrosis: a common breast lesion diagnosed at imaging-guided core biopsy." AJR Am J Roentgenol 173.6 (December 1999): 1657-1662.
PMID
10584816
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
173
Issue
6
Publish Date
1999
Start Page
1657
End Page
1662
DOI
10.2214/ajr.173.6.10584816

Epidemiologic and surgicopathologic findings of papillary serous and clear cell endometrial cancers when compared to endometrioid carcinoma.

PURPOSE: The aim of this study was to identify similarities and differences in epidemiologic and surgicopathologic staging results for papillary serous (PS) and clear cell (CC) endometrial cancers compared with endometrioid (EM) carcinoma of the endometrium. METHODS: Clinical and surgicopathologic data were retrospectively collected on 574 clinical stage I-II endometrial cancer patients, including 53 PS and 18 CC (based on postoperative histology), undergoing hysterectomy at Duke University Medical Center between 1967 and 1990. All staging material was available and reexamined prior to this analysis, and FIGO surgical staging was retrospectively assigned. PS and CC histologic subtypes were compared both as a common category and as discrete categories versus EM, EM grade 1 (EM1), EM grade 2 (EM2), and EM grade 3 (EM3). Fisher's exact test was used to compare proportions with unordered categories (2x2 tables), while the chi(2) test for trend was used to compare proportions in 3x2 tables with ordered categories. Differences in medians were compared with the Wilcoxon rank-sum test. RESULTS: PS tumors accounted for 8%, CC for 2%, and EM for 90% of cases. Overall, 14% of tumors were changed to a different postoperative histology including 64% of PS, 50% of CC, and 8% of EM. Postoperative histology changes were 4% for EM1 and 21% for EM3. PS, CC, and EM3 had more surgical sampling performed than for other EM. Rates for lymph node dissections were similar for EM3 (81%), PS (72%), and CC (67%) tumors, although metastases were more frequent for PS and CC compared with EM3. When PS tumors were confined to the endometrium, paraaortic metastases occurred in 13%. LVSI increased with EM grade and was highest for PS and CC. Upstaging to surgical stage III-IV occurred in 47% of PS, 39% of CC, and 12% of EM. The majority of PS and CC tumors were confined to the inner one-third of the myometrium, compared with EM tumors, where grade correlated with depth of myometrial invasion. Extrauterine metastases occurred in 55% of PS and 45% of CC tumors confined to the inner one-half, compared with 17% of EM3. CONCLUSION: Frequent changes from preoperative to postoperative histology and grade may contribute to misassignment of preoperative and intraoperative risk as determined by depth of myometrial invasion for PS and CC patients. The higher frequency of extrauterine metastases in PS and CC tumors compared with EM3, despite similar surgical sampling rates, supports a more virulent behavior. The poor correlation between depth of myometrial invasion and risk for extrauterine metastases helps to explain poorer survival in PS and CC patients, in addition to more frequent upstaging. These results support routine extended surgical staging for women with preoperative or intraoperative diagnosis of PS and CC tumors. Intraoperative assessment of tumor grade and histology may be indicated and warrants further investigation.

Authors
Cirisano, FD; Robboy, SJ; Dodge, RK; Bentley, RC; Krigman, HR; Synan, IS; Soper, JT; Clarke-Pearson, DL
MLA Citation
Cirisano, FD, Robboy, SJ, Dodge, RK, Bentley, RC, Krigman, HR, Synan, IS, Soper, JT, and Clarke-Pearson, DL. "Epidemiologic and surgicopathologic findings of papillary serous and clear cell endometrial cancers when compared to endometrioid carcinoma." Gynecol Oncol 74.3 (September 1999): 385-394.
PMID
10479498
Source
pubmed
Published In
Gynecologic Oncology
Volume
74
Issue
3
Publish Date
1999
Start Page
385
End Page
394
DOI
10.1006/gyno.1999.5505

Meningioma of the fourth ventricle.

Meningiomas are primary meningeal based tumors of the central nervous system that rarely are located strictly within the fourth ventricle. We report a 72-year-old man operated upon for such a tumor. The pre-operative magnetic resonance images revealed a well circumscribed mass in the fourth ventricle that exhibited a low signal on T1-weighted magnetic resonance images and homogenously enhanced with gadolinium. By light microscopy the tumor was composed of tightly packed spindle cells separated by collagen. Immunohistochemistry showed the tumor cells to be positive for vimentin and epithelial membrane antigen, and negative for glial fibrillary acidic protein. Electron microscopy revealed typical findings of meningioma, including interdigitating cell processes, desmosomes, and intermediate filaments. Although rare, fibroblastic meningioma must be included in the differential diagnosis of a fourth ventricular spindle cell tumor in elderly patients.

Authors
Cummings, TJ; Bentley, RC; Gray, L; Check, WE; Lanier, TE; McLendon, RE
MLA Citation
Cummings, TJ, Bentley, RC, Gray, L, Check, WE, Lanier, TE, and McLendon, RE. "Meningioma of the fourth ventricle." Clin Neuropathol 18.5 (September 1999): 265-269.
PMID
10505436
Source
pubmed
Published In
Clinical neuropathology
Volume
18
Issue
5
Publish Date
1999
Start Page
265
End Page
269

Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver.

BACKGROUND: Ischemic injury of the liver is generally considered to result in necrosis, but it has recently been recognized that mediators of apoptosis are activated during ischemia/reperfusion. This study was designed to characterize the extent and the type of cells within the liver that undergo apoptosis at different periods of ischemia and reperfusion. METHODS: Male Wistar rats were subjected to 30 or 60 min of normothermic ischemia. Liver sections were evaluated at the end of ischemia and at 1, 6, 24, and 72 hr after reperfusion. Apoptosis was determined by DNA fragmentation as evaluated by laddering on gel electrophoresis, in situ staining for apoptotic cells using TdT-mediated dUTP-digoxigenin nick-end labeling (TUNEL), and morphology on electron microscopy. RESULTS: In situ staining of liver biopsy specimens using TUNEL showed significant apoptosis after reperfusion. Sinusoidal endothelial cells (SEC) showed evidence of apoptosis earlier than hepatocytes. For example, at 1 hr of reperfusion after 60 min of ischemia, 22+/-4% of the SEC stained TUNEL positive compared with 2+/-1% of the hepatocytes (P<0.001). With a longer duration of ischemia, a greater number of SEC and hepatocytes became TUNEL positive. An increase in TUNEL-positive cells was also noted with an increasing duration of reperfusion. The presence of apoptotic SEC and hepatocytes was supported by DNA laddering on gel electrophoresis and cell morphology on electron microscopy. Several Kupffer cells were seen containing apoptotic bodies but did not show evidence of apoptosis. Only rare hepatocytes showed features of necrosis after 60 min of ischemia and 6 hr of reperfusion. CONCLUSION: These results suggest that apoptosis of endothelial cells followed by hepatocytes is an important mechanism of cell death after ischemia/reperfusion injury in the liver.

Authors
Kohli, V; Selzner, M; Madden, JF; Bentley, RC; Clavien, PA
MLA Citation
Kohli, V, Selzner, M, Madden, JF, Bentley, RC, and Clavien, PA. "Endothelial cell and hepatocyte deaths occur by apoptosis after ischemia-reperfusion injury in the rat liver." Transplantation 67.8 (April 27, 1999): 1099-1105.
PMID
10232558
Source
pubmed
Published In
Transplantation
Volume
67
Issue
8
Publish Date
1999
Start Page
1099
End Page
1105

Malignant melanoma presenting as a mediastinal mass.

A case of malignant melanoma presenting as a mediastinal mass without an extrathoracic primary is reported. Microscopically the tumor appeared consistent with malignant melanoma, with the presence of focal melanin pigment in large epithelioid cells. Fontana stain confirmed the presence of melanin pigment. Immunohistochemical staining further suggested melanoma, with the tumor cells expressing a HMB45+, S100+ and cytokeratin-phenotype. Electron microscopy showed an abundance of melanosomes confirming the diagnosis of malignant melanoma.

Authors
Lau, CL; Bentley, RC; Gockerman, JP; Que, LG; D'Amico, TA
MLA Citation
Lau, CL, Bentley, RC, Gockerman, JP, Que, LG, and D'Amico, TA. "Malignant melanoma presenting as a mediastinal mass." Ann Thorac Surg 67.3 (March 1999): 851-852.
PMID
10215250
Source
pubmed
Published In
The Annals of Thoracic Surgery
Volume
67
Issue
3
Publish Date
1999
Start Page
851
End Page
852

Pseudoanaplastic giant cell tumor of bone.

Marked nuclear atypia can be found in a variety of benign mesenchymal tumors, including ancient schwannomas, symplastic leiomyomas, osteoblastomas, and chondromyxoid fibromas. Such nuclear atypia is believed to represent a degenerative phenomenon and does not indicate aggressive behavior. Separation of these pleomorphic but benign lesions from true sarcomas may be difficult. We are aware of only one prior description of such degenerative atypia in benign giant cell tumor of bone. We report a benign giant cell tumor of bone arising in the sacrum of a 21-year-old white female. Preoperative embolization of this lesion had been performed, and subsequent curetting revealed marked atypia suggestive of an anaplastic malignancy. However, only very rare mitotic figures were present, and the radiographs were consistent with a benign giant cell tumor. A diagnosis of benign giant cell tumor was made, and no recurrence or metastases have been observed during the 4-year postoperative period.

Authors
Layfield, LJ; Bentley, RC; Mirra, JM
MLA Citation
Layfield, LJ, Bentley, RC, and Mirra, JM. "Pseudoanaplastic giant cell tumor of bone." Arch Pathol Lab Med 123.2 (February 1999): 163-166.
PMID
10050793
Source
pubmed
Published In
Archives of Pathology and Laboratory Medicine
Volume
123
Issue
2
Publish Date
1999
Start Page
163
End Page
166
DOI
10.1043/0003-9985(1999)123<0163:PGCTOB>2.0.CO;2

Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis.

BACKGROUND & AIMS: Calpain proteases have been implicated in cell death by necrosis and more recently by apoptosis. Experiments were designed to determine the role of calpain proteases in ischemic rat liver injury by measurement of cytosolic calpain activity after different periods of ischemia-reperfusion and by evaluation of the effects of calpain inhibition on tissue injury and animal survival. METHODS: Calpain activity was measured in the cytosol using Suc-Leu-Leu-Val-Try-7 amino-4 methyl coumarin, a specific fluorogenic substrate, and Cbz-Leu-Leu-Tyr-CHN2, a specific inhibitor. RESULTS: Calpain activity increased significantly with the duration of ischemia-reperfusion and was inhibited more than 80% by the inhibitor. Calpain inhibition resulted in a significant decrease in transaminase release and tissue necrosis and converted nonsurvival ischemic conditions to survival conditions. When the in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling assay for apoptosis was used, 35% +/- 6% of nonparenchymal cells and 16% +/- 3% of hepatocytes stained positively after 60 minutes of ischemia and 6 hours of reperfusion. In contrast, animals pretreated with the calpain inhibitor showed minimal evidence of apoptosis. This was further substantiated by gel electrophoresis assay for DNA fragmentation and by electron-microscopic evaluation. CONCLUSIONS: These data suggest that calpain proteases play a pivotal role in warm ischemia-reperfusion injury of the rat liver through modulation of apoptosis and necrosis.

Authors
Kohli, V; Madden, JF; Bentley, RC; Clavien, PA
MLA Citation
Kohli, V, Madden, JF, Bentley, RC, and Clavien, PA. "Calpain mediates ischemic injury of the liver through modulation of apoptosis and necrosis." Gastroenterology 116.1 (January 1999): 168-178.
PMID
9869615
Source
pubmed
Published In
Gastroenterology
Volume
116
Issue
1
Publish Date
1999
Start Page
168
End Page
178

Critical commentary to Cotyledonoid dissecting leiomyoma (Sternberg tumor): An unusual form of leiomyoma

Authors
Bentley, RC; Robboy, SJ
MLA Citation
Bentley, RC, and Robboy, SJ. "Critical commentary to Cotyledonoid dissecting leiomyoma (Sternberg tumor): An unusual form of leiomyoma." Pathology Research and Practice 195.6 (1999): 439--.
Source
scival
Published In
Pathology Research and Practice
Volume
195
Issue
6
Publish Date
1999
Start Page
439-

Villoglandular adenocarcinoma of the endometrium: a clinicopathologic study of 61 cases: a gynecologic oncology group study.

Papillary endometrioid or villoglandular adenocarcinoma (VGA) is a relatively common type of endometrial adenocarcinoma, but studies describing its behavior have yielded conflicting results. Patients with a component of VGA were identified in a review of 819 women entered in a Gynecology Oncology Group Study (Protocol 33) of clinical stages I and II endometrial adenocarcinoma. Cases with coexisting foci of serous or clear cell carcinoma were excluded from further consideration. Of the 61 cases that formed the study sample, there were 24 with pure villoglandular differentiation and 37 who were admixed with typical endometrioid adenocarcinoma (EA). The general clinicopathologic features of patients with pure and mixed VGA are compared with 469 patients with pure EA. The VGAs were better differentiated (grade 1 or 2--97% of VGA versus 74% EA, p = 0.001). but they were not significantly different with respect to median age, depth of invasion, or frequency of nodal spread. Six of the 61 patients with VGA died of their tumor. The disease-specific survival rate at 3 years for VGA is 94% (95% confidence interval: 0.88-0.99) compared with 88% (95% CI: 0.86-0.91) for EA. Two of the patients who died had pure villoglandular tumors and four had mixed villoglandular and endometrioid carcinoma. In view of the frequent admixture of VGA and EA and their generally similar biological characteristics, with a prognosis similar to that of typical EA, we conclude that VGA should be considered a variant of EA.

Authors
Zaino, RJ; Kurman, RJ; Brunetto, VL; Morrow, CP; Bentley, RC; Cappellari, JO; Bitterman, P
MLA Citation
Zaino, RJ, Kurman, RJ, Brunetto, VL, Morrow, CP, Bentley, RC, Cappellari, JO, and Bitterman, P. "Villoglandular adenocarcinoma of the endometrium: a clinicopathologic study of 61 cases: a gynecologic oncology group study." Am J Surg Pathol 22.11 (November 1998): 1379-1385.
PMID
9808130
Source
pubmed
Published In
American Journal of Surgical Pathology
Volume
22
Issue
11
Publish Date
1998
Start Page
1379
End Page
1385

Goblet-cell mucinous epithelium lining the endometrium and endocervix: evidence of metastasis from an appendiceal primary tumor through the use of cytokeratin-7 and -20 immunostains.

Differential staining with cytokeratin (CK)-7 and CK-20, two members of a complex family of proteins in human epithelial cells, proved critical in showing that the extremely well-differentiated goblet-cell (intestinal) mucinous epithelium lining the surface of the endometrium and endocervix in two patients and the fallopian tube in one was identical to that of the coincident appendiceal neoplasms. One of these patients also had a large ovarian tumor that grossly and microscopically resembled a mucinous cystadenoma of borderline malignancy and would have been considered primary except for the CK stains (CK-20 positive and CK-7 negative), which suggested metastasis from the appendix, presumably by a transtubal route.

Authors
Moore, WF; Bentley, RC; Kim, KR; Olatidoye, B; Gray, SR; Robboy, SJ
MLA Citation
Moore, WF, Bentley, RC, Kim, KR, Olatidoye, B, Gray, SR, and Robboy, SJ. "Goblet-cell mucinous epithelium lining the endometrium and endocervix: evidence of metastasis from an appendiceal primary tumor through the use of cytokeratin-7 and -20 immunostains." Int J Gynecol Pathol 17.4 (October 1998): 363-367.
PMID
9785138
Source
pubmed
Published In
International Journal of Gynecological Pathology
Volume
17
Issue
4
Publish Date
1998
Start Page
363
End Page
367

Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias.

Mutation and deletion of the PTEN tumor suppressor gene occurs in about 40% of endometrial carcinomas. The purpose of this study was to determine whether PTEN mutations also are present in endometrial hyperplasias, which are premalignant precursors of invasive endometrial adenocarcinomas. Genomic DNA from 51 endometrial hyperplasias was extracted from paraffin blocks, and PCR was used to amplify the nine exons of the PTEN gene. These products were screened using single-strand conformation analysis, and variant bands were sequenced. Somatic mutations in the PTEN gene were seen in 10 of 51 cases (20%), and two mutations were found in one case. An identical 4-bp deletion in exon 8 was seen in three cases, and 8 of 11 PTEN mutations predicted truncated protein products. There was no higher frequency of PTEN mutations in endometrial hyperplasias with atypia (6 of 32; 19%) relative to those without atypia (4 of 19; 21%). These data suggest that inactivation of the PTEN tumor suppressor gene is an early event in the development of some endometrial cancers.

Authors
Maxwell, GL; Risinger, JI; Gumbs, C; Shaw, H; Bentley, RC; Barrett, JC; Berchuck, A; Futreal, PA
MLA Citation
Maxwell, GL, Risinger, JI, Gumbs, C, Shaw, H, Bentley, RC, Barrett, JC, Berchuck, A, and Futreal, PA. "Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias." Cancer Res 58.12 (June 15, 1998): 2500-2503.
PMID
9635567
Source
pubmed
Published In
Cancer Research
Volume
58
Issue
12
Publish Date
1998
Start Page
2500
End Page
2503

Apoptosis of sinusoidal endothelial cells is a critical mechanism of preservation injury in rat liver transplantation.

In livers excised for transplantation, sinusoidal endothelium appears especially vulnerable to injury during organ preservation in the cold and subsequent reperfusion. The degree of endothelial cell injury correlates with functional impairment of the graft following transplantation. The mechanism of injury remains obscure, but endothelial cell damage has been described as coagulative necrosis secondary to irreversible physico-chemical damage. We investigated whether endothelial cell death is caused by apoptosis rather than by necrosis. Tissue from rat livers stored for varying periods in cold (1 degree C) Euro-Collins solution and then reperfused for 1 hour at 37 degrees C were studied for evidence of apoptosis by detection of DNA fragmentation using the in situ terminal deoxynucleotidyl transferase d-uridine triphosphate nick end labeling (TUNEL) assay, DNA gel electrophoresis, and by transmission electron microscopy (EM). DNA fragmentation of the type characteristic of apoptosis was identified in 49.7% +/- 2.2% of sinusoidal lining cells after 8 hours of ischemia + reperfusion (viable graft) vs. 70.7% +/- 4.3% after 16 hours + reperfusion (nonviable graft) (P < .001). No such fragmentation was observed after cold preservation without reperfusion or in unpreserved, reperfused livers. EM demonstrated changes characteristic of apoptosis exclusively in endothelial cells. The study suggests that the apoptosis of sinusoidal endothelial cells is a pivotal mechanism of preservation injury in liver transplantation.

Authors
Gao, W; Bentley, RC; Madden, JF; Clavien, PA
MLA Citation
Gao, W, Bentley, RC, Madden, JF, and Clavien, PA. "Apoptosis of sinusoidal endothelial cells is a critical mechanism of preservation injury in rat liver transplantation." Hepatology 27.6 (June 1998): 1652-1660.
PMID
9620339
Source
pubmed
Published In
Hepatology
Volume
27
Issue
6
Publish Date
1998
Start Page
1652
End Page
1660
DOI
10.1002/hep.510270626

Solitary fibrous tumor of the meninges occurring after irradiation of a mixed germ cell tumor of the pineal gland.

Twenty-nine months after surgery, irradiation, and systemic chemotherapy for a pineal mixed germ cell tumor, an 11-year-old Caucasian male developed a 3 cm dural based nodule in the occipital lobe that proved to be a solitary fibrous tumor by immunohistochemical and ultrastructural examination. Differential diagnosis included fibrous meningioma, neurofibroma, Schwannoma, cranial fasciitis of infancy, and solitary fibrous tumor. A Masson trichrome stain revealed a prominent collagenous stroma and reticulin staining exhibited strong pericellular positivity. Immunohistochemical staining demonstrated diffuse vimentin and focal CD34 positivity of tumor cells. Ultrastructural examination revealed fibroblastic differentiation. These features are consistent with solitary fibrous tumor. Although we favor a radiation-induced origin for the neoplasm, alternative explanations for the tumor's origin include cerebrospinal fluid spread from the original germ cell tumor or a de novo neoplasm.

Authors
Slavik, T; Bentley, RC; Gray, L; Fuchs, HE; McLendon, RE
MLA Citation
Slavik, T, Bentley, RC, Gray, L, Fuchs, HE, and McLendon, RE. "Solitary fibrous tumor of the meninges occurring after irradiation of a mixed germ cell tumor of the pineal gland." Clin Neuropathol 17.1 (January 1998): 55-60.
PMID
9496542
Source
pubmed
Published In
Clinical neuropathology
Volume
17
Issue
1
Publish Date
1998
Start Page
55
End Page
60

Antiangiogenic agents protect liver sinusoidal lining cells from cold preservation injury in rat liver transplantation.

BACKGROUND & AIMS: Low temperature preservation causes unique liver injuries to the sinusoidal lining cells characterized by endothelial cell detachment and rounding and Kupffer cell activation. These changes are similar to those observed during the early stages of angiogenesis. The aim of this study was to investigate if cold preservation injury is caused by the activation of angiogenic mechanisms. METHODS: Livers were obtained from rats pretreated with three well-known antiangiogenic agents (minocycline, interferon alfa-2b, and fumagillin) and were stored for various durations in cold preservation solutions. The effects of the drugs were evaluated by morphometric assessment of endothelial cell injury in H&E, trypan blue, and immunostained (TIE2/Tek) biopsy specimens. Graft functions and survival were evaluated in isolated perfused rat liver and arterialized orthotopic liver transplantation models. RESULTS: Sinusoidal lining cell integrity and viability were significantly improved in animals pretreated with the drugs. Reperfusion injury and survival were also better in pretreated animals. Interferon alfa was the most potent agent, reducing injury even in livers preserved in the current most commonly used solution (University of Wisconsin solution). CONCLUSIONS: Cold preservation injury of liver may be the results of angiogenic mechanisms. This novel observation provides a rationale for improved liver preservation using antiangiogenic agents.

Authors
Gao, W; Washington, MK; Bentley, RC; Clavien, PA
MLA Citation
Gao, W, Washington, MK, Bentley, RC, and Clavien, PA. "Antiangiogenic agents protect liver sinusoidal lining cells from cold preservation injury in rat liver transplantation." Gastroenterology 113.5 (November 1997): 1692-1700.
PMID
9352874
Source
pubmed
Published In
Gastroenterology
Volume
113
Issue
5
Publish Date
1997
Start Page
1692
End Page
1700

Gastric graft-versus-host disease: a blinded histologic study.

Acute graft-versus-host disease (GvHD) of the upper gastrointestinal (GI) tract is common after allogeneic bone marrow transplantation (BMT). However, diagnosis cannot be made on clinical presentation and endoscopic findings alone, because these are nonspecific, and histologic confirmation is often desirable. The diagnosis of gastric GvHD is often based on subtle findings with considerable potential for variability in interpretation. Evaluation of the reproducibility of diagnosis and recognition of histologic features of gastric GvHD was based on blinded review of 56 gastric biopsies (24 from patients with allogeneic BMT or unrelated umbilical cord blood transplantation and 32 control biopsies from patients who did not undergo BMT, of whom eight had active GI cytomegalovirus [CMV] infection). Histologic criteria for GvHD were apoptosis and gland destruction, sparse inflammatory infiltrate, and granular eosinophilic debris in dilated glands. Seventeen patients (22 biopsies) were judged to have clinical GvHD on the basis of skin or liver involvement and GI symptoms without other known cause. Eighteen of these 22 gastric biopsies were classified as GvHD by at least two of the three pathologists on initial review. Blinded histologic diagnosis of GvHD had a positive predictive value of 69%, a sensitivity of 82%, and specificity of 76%. False-positive results occurred in CMV gastritis, human immunodeficiency virus (HIV) infection, primary immunodeficiency, and after renal transplantation. Of individual features, granular debris in glands was a specific (94% specificity), but insensitive (41% sensitivity) marker for GvHD. Distinction between GvHD and CMV infection can be difficult, and GvHD can be confused with changes seen in HIV infection and other immunodeficiency states.

Authors
Washington, K; Bentley, RC; Green, A; Olson, J; Treem, WR; Krigman, HR
MLA Citation
Washington, K, Bentley, RC, Green, A, Olson, J, Treem, WR, and Krigman, HR. "Gastric graft-versus-host disease: a blinded histologic study." Am J Surg Pathol 21.9 (September 1997): 1037-1046.
PMID
9298880
Source
pubmed
Published In
American Journal of Surgical Pathology
Volume
21
Issue
9
Publish Date
1997
Start Page
1037
End Page
1046

Malignant supratentorial glial-neuronal neoplasms: report of two cases and review of the literature.

OBJECTIVE: Malignant neoplasms exhibiting mixed populations of neuronal and glial cells occurring in the cerebral hemispheres of young adults and children are well recognized, but rare. A confusing array of diagnostic terms has arisen. We describe two patients with such tumors and review the literature concerning these interesting cases. PATIENTS: A 21-year-old man and a 5-year-old girl presented with large, cystic, intracerebral lesions on magnetic resonance images, which proved to be composite neoplasms exhibiting malignant neurons and astrocytes. RESULTS: The 21-year-old man had a frontal lobe mass with enhancing and nonenhancing regions, which corresponded to cerebral neuroblastoma and anaplastic astrocytoma, respectively. The presence of occasional microtubules and rare primitive presynaptic processes, accompanied by antisynaptophysin immunoreactivity, established the neuronal nature of the cells in the enhancing region. The nonenhancing region was composed of a moderately cellular neoplasm of fibrillar astrocytes that were mitotically active. The 5-year-old girl presented with a left parietal lobe neoplasm, which histologically was composed of lobular proliferations of neuroblasts and glia. The neuroblastic populations exhibited evidence of maturation with small anaplastic cells, spindle-shaped cells, and large dysmorphic ganglion cells. The glial tumor showed both well-differentiated fibrillary astrocytes with microcysts and anaplastic populations with central necrosis and pseudopalisading. CONCLUSIONS: Present classification systems devised to describe mixed neuronal and glial tumors do not adequately encompass the diversity of morphologies presented by these two cases. We conclude that the terms cerebral neuroblastoma-anaplastic astrocytoma for case 1 and cerebral ganglioneuroblastoma-glioblastoma for case 2 are preferred because they convey useful clinical information by reflecting concepts already encompassed by the World Health Organization's classification system of tumors of the central nervous system.

Authors
McLendon, RE; Bentley, RC; Parisi, JE; Tien, RD; Harrison, JC; Tarbell, NJ; Billitt, AL; Gualtieri, RJ; Friedman, HS
MLA Citation
McLendon, RE, Bentley, RC, Parisi, JE, Tien, RD, Harrison, JC, Tarbell, NJ, Billitt, AL, Gualtieri, RJ, and Friedman, HS. "Malignant supratentorial glial-neuronal neoplasms: report of two cases and review of the literature." Arch Pathol Lab Med 121.5 (May 1997): 485-492. (Review)
PMID
9167602
Source
pubmed
Published In
Archives of Pathology and Laboratory Medicine
Volume
121
Issue
5
Publish Date
1997
Start Page
485
End Page
492

Human endometrial transforming growth factor-alpha: a transmembrane, surface epithelial protein that transiently disappears during the midsecretory phase of the menstrual cycle.

OBJECTIVES: To characterize the forms of transforming growth factor-alpha (TGF-alpha) in normal human endometrium, to evaluate the regional and temporal changes in TGF-alpha expression, and to correlate the pattern of TGF-alpha expression with physiologic events in the endometrium. METHODS: Immunohistochemistry and Western blot analyses were performed using two TGF-alpha antisera, one raised against the active extracellular N-terminus and the other recognizing the intracellular carboxy terminus of the protein. Immunohistochemistry was performed on hysterectomy specimens from premenopausal women with normal menstrual cycles. Soluble and membrane-bound endometrial proteins were isolated from fresh tissue for Western blot analysis. RESULTS: Antibodies recognizing the intracellular and extracellular domains of TGF-alpha exhibited identical immunohistochemical staining patterns. Transforming growth factor-alpha localized primarily to endometrial epithelial cells, and the most intense staining was in the luminal surface epithelium. In the surface epithelium, TGF-alpha staining was intense in the proliferative phase, decreased during the early secretory phase, was at its nadir in the midsecretory phase, and rebounded in the late secretory phase. Western blot analysis demonstrated two transmembrane forms. The 28-kD protein contained both intracellular and extracellular antigens, and the 18-kD protein contained only the intracellular antigen. CONCLUSION: Western blot data were consistent with the hypothesis that the extracellular segment of TGF-alpha is cleaved from the transmembrane precursor in vivo, as has been demonstrated in other tissues. Immunohistochemistry demonstrated that the TGF-alpha antigens are concentrated in the luminal surface epithelium and decline and disappear in the early to midsecretory phase. These findings suggest that the most active period of membrane-bound TGF-alpha cleavage corresponds with the interval during which preimplantation embryos are in the uterine cavity.

Authors
Hansard, LJ; Healy-Gardner, BE; Drapkin, AT; Bentley, RC; McLachlan, JA; Walmer, DK
MLA Citation
Hansard, LJ, Healy-Gardner, BE, Drapkin, AT, Bentley, RC, McLachlan, JA, and Walmer, DK. "Human endometrial transforming growth factor-alpha: a transmembrane, surface epithelial protein that transiently disappears during the midsecretory phase of the menstrual cycle." J Soc Gynecol Investig 4.3 (May 1997): 160-166.
PMID
9258881
Source
pubmed
Published In
Journal of the Society for Gynecologic Investigation (Elsevier)
Volume
4
Issue
3
Publish Date
1997
Start Page
160
End Page
166

Signet-ring cell carcinoma of the endometrium: a primary tumor masquerading as a metastasis.

Extragenital metastases to the endometrium are unusual, but several histologic features have been suggested as highly suggestive or even pathognomonic for this diagnosis. We report an endometrial carcinoma with a prominent signet-ring cell morphology and a diffusely permeative pattern of infiltration, features that have been reported as indicating an extragenital metastasis. To the best of our knowledge, this is the first reported case of a signet-ring cell carcinoma of the endometrium. Gynecological pathologists should be aware of this entity because of its potential primary of metastatic signet-ring carcinoma to be endometrium.

Authors
Mooney, EE; Robboy, SJ; Hammond, CB; Berchuck, A; Bentley, RC
MLA Citation
Mooney, EE, Robboy, SJ, Hammond, CB, Berchuck, A, and Bentley, RC. "Signet-ring cell carcinoma of the endometrium: a primary tumor masquerading as a metastasis." Int J Gynecol Pathol 16.2 (April 1997): 169-172.
PMID
9100072
Source
pubmed
Published In
International Journal of Gynecological Pathology
Volume
16
Issue
2
Publish Date
1997
Start Page
169
End Page
172

Implantation metastasis of primary malignant rhabdoid tumor of the brain in an adult (one case report).

Primary malignant rhabdoid tumor (PMRT) of the brain is a rare and recently described neoplasm of youth. We report magnetic resonance imaging (MRI), computed tomography (CT), and pathology of one case of PMRT in an adult which seeded along the needle track for stereotactic biopsy.

Authors
Ashraf, R; Bentley, RC; Awan, AN; McLendon, RE; Ragozzino, MW
MLA Citation
Ashraf, R, Bentley, RC, Awan, AN, McLendon, RE, and Ragozzino, MW. "Implantation metastasis of primary malignant rhabdoid tumor of the brain in an adult (one case report)." Med Pediatr Oncol 28.3 (March 1997): 223-227.
PMID
9024522
Source
pubmed
Published In
Pediatric Blood and Cancer
Volume
28
Issue
3
Publish Date
1997
Start Page
223
End Page
227

p53lyn and p56lyn: a new signaling pathway in human endometrium and endometrial adenocarcinomas.

OBJECTIVE: To identify specific tyrosine kinases that are involved in endometrial signaling and to study their in vivo expression in normal and abnormal endometrium. We hypothesized that proteins that are differentially expressed would be more likely to be important in regulated cellular events. METHODS: Complementary DNA libraries, constructed from human secretory (n = 5) and proliferative (n = 5) endometrial specimens, were screened with a polyclonal anti-phosphotyrosine antibody. Positive clones were sequenced and screened for differential expression using immunoblotting and Northern analysis of samples from proliferative and secretory endometrium. The expression of one identified clone, lyn, a Src family member, was characterized further with Western and Northern blot analyses and immunolocalization. RESULTS: One protein identified by the above method was lyn, a member of the src family of protein tyrosine kinases, never before described in the human endometrium. Western blot analysis revealed two forms of lyn protein, p53lyn and p56lyn, that were most abundant in the late secretory phase. Immunohistochemistry demonstrated uniform protein expression by all cells in normal glandular epithelium and suggested a correlation between lyn protein expression and cell differentiation for human endometrial adenocarcinomas, with markedly-elevated levels noted in poorly differentiated adenocarcinomas compared with well-differentiated tumors (n = 3). Northern hybridization confirmed the presence of the expected 3.5-kb lyn transcript in normal and abnormal endometrium. CONCLUSIONS: Our data demonstrate that human cDNA libraries created from different phases of the menstrual cycle can be screened successfully using anti-phosphotyrosine antibodies to identify differentially expressed protein tyrosine kinases. Although p53lyn and p56lyn expression has been thought of as a predominantly lymphoid-specific tyrosine kinase, we show prominent expression of lyn protein and mRNA by normal and malignant epithelium of the human endometrium, suggesting a role in endometrial signaling and human reproduction.

Authors
Couchman, GM; Bentley, R; Tsao, MS; Raszmann, K; McLachlan, JA; Walmer, DK
MLA Citation
Couchman, GM, Bentley, R, Tsao, MS, Raszmann, K, McLachlan, JA, and Walmer, DK. "p53lyn and p56lyn: a new signaling pathway in human endometrium and endometrial adenocarcinomas." J Soc Gynecol Investig 4.2 (March 1997): 103-109.
PMID
9101470
Source
pubmed
Published In
Journal of the Society for Gynecologic Investigation (Elsevier)
Volume
4
Issue
2
Publish Date
1997
Start Page
103
End Page
109

Implantation metastasis of primary malignant rhabdoid tumor of the brain in an adult (one case report)

Primary malignant rhabdoid tumor (PMRT) of the brain is a rare and recently described neoplasm of youth. We report magnetic resoonance imaging (MRI), computed tomography (C↑), and pathology of one case of PMRT in an adult which seeded along the needle track for stereotactic biopsy.

Authors
Ashraf, R; Bentley, RC; Awan, AN; McLendon, RE; Ragozzino, MW
MLA Citation
Ashraf, R, Bentley, RC, Awan, AN, McLendon, RE, and Ragozzino, MW. "Implantation metastasis of primary malignant rhabdoid tumor of the brain in an adult (one case report)." Medical and Pediatric Oncology 28.3 (February 25, 1997): 223-227.
Source
scopus
Published In
Pediatric Blood and Cancer
Volume
28
Issue
3
Publish Date
1997
Start Page
223
End Page
227
DOI
10.1002/(SICI)1096-911X(199703)28:3<223::AID-MPO14>3.0.CO;2-F

Aneurysmal bone cyst formation within a chondroblastoma: case report.

Authors
Garces, PB; Melamed, JW; Martinez, S; Bentley, RC
MLA Citation
Garces, PB, Melamed, JW, Martinez, S, and Bentley, RC. "Aneurysmal bone cyst formation within a chondroblastoma: case report." Can Assoc Radiol J 48.1 (February 1997): 25-27.
PMID
9030065
Source
pubmed
Published In
Canadian Association of Radiologists Journal
Volume
48
Issue
1
Publish Date
1997
Start Page
25
End Page
27

The detection of breast microcalcifications with medical ultrasound.

Microcalcifications are small crystals of calcium apatites which form in human tissue through a number of mechanisms. The size, morphology, and distribution of microcalcifications are important indicators in the mammographic screening for and diagnosis of various carcinomas in the breast. Although x-ray mammography is currently the only accepted method for detecting microcalcifications, its efficacy in this regard can be reduced in the presence of dense parenchyma. Current ultrasound scanners do not reliably detect microcalcifications in the size range of clinical interest. The results of theoretical, simulation, and experimental studies focused on the improvement of the ultrasonic visualization of microcalcifications are presented. Methods for estimating the changes in microcalcification detection performance which result from changes in aperture geometry or the presence of an aberrator are presented. An analysis of the relative efficacy of spatial compounding and synthetic receive aperture geometries in the detection of microcalcifications is described. The impact of log compression of the detected image on visualization is discussed. Registered high resolution ultrasound and digital spot mammography images of microcalcifications in excised breast carcinoma tissue and results from the imaging of suspected microcalcifications in vivo are presented.

Authors
Anderson, ME; Soo, MS; Bentley, RC; Trahey, GE
MLA Citation
Anderson, ME, Soo, MS, Bentley, RC, and Trahey, GE. "The detection of breast microcalcifications with medical ultrasound." J Acoust Soc Am 101.1 (January 1997): 29-39.
PMID
9000730
Source
pubmed
Published In
The Journal of the Acoustical Society of America
Volume
101
Issue
1
Publish Date
1997
Start Page
29
End Page
39

Axillary lymph nodes: mammographic, pathologic, and clinical correlation.

OBJECTIVE: The purpose of this study was to determine the cause and frequency of axillary abnormalities seen mammographically and to evaluate the imaging characteristics of lymphadenopathy that are associated with malignancy. MATERIALS AND METHODS: Ninety-six axillary abnormalities seen mammographically in 94 patients were retrospectively reviewed and correlated with the clinical diagnoses and pathologic results found in the medical records. For each abnormality, the length, margins, and presence of microcalcifications were noted. Logistic regression was used to determine an association between these findings and status (benign or malignant). RESULTS: Seventy-six of 94 patients had lymphadenopathy. Eighteen of 94 patients had an abnormality other than lymphadenopathy. Because two of these 94 patients had more than one abnormality, a total of 96 abnormalities occurred, 20 of which were due to an abnormality other than lymphadenopathy. Regarding the 76 cases of lymphadenopathy, the most frequent diagnosis was nonspecific benign lymphadenopathy in 29% (n = 22) of cases, followed by metastatic breast cancer in 26% (n = 20) and chronic lymphocytic leukemia or well-differentiated lymphocytic lymphoma in 17% (n = 13). Other causes (n = 21) included collagen vascular disease, lymphomas other than well-differentiated lymphocytic lymphoma, metastatic disease from nonbreast primary site, metastatic disease from unknown primary site, sarcoidosis. HIV-related lymphadenopathy, and reactive lymphadenopathy associated with a breast abscess. An association between length of nonfatty lymph nodes and malignant status was statistically significant at the .001 level. When a length greater than 33 mm was used as a predictor of malignancy, the specificity and sensitivity were 97% and 31%, respectively. We found an association between malignancy and nonfatty lymph nodes with ill-defined or spiculated margins (p = .053). Regarding the 20 abnormalities other than lymphadenopathy, epidermal cysts (n = 7) were most prevalent. CONCLUSION: The most common axillary abnormality revealed on mammography was abnormal lymph nodes. Homogeneously dense (nonfatty) axillary lymph nodes were strongly associated with malignancy when the lymph nodes were longer than 33 mm, had ill-defined or spiculated margins, or contained intranodal microcalcifications. However, our study confirmed that in most cases benign and malignant lymph nodes cannot be distinguished from each other mammographically.

Authors
Walsh, R; Kornguth, PJ; Soo, MS; Bentley, R; DeLong, DM
MLA Citation
Walsh, R, Kornguth, PJ, Soo, MS, Bentley, R, and DeLong, DM. "Axillary lymph nodes: mammographic, pathologic, and clinical correlation." AJR Am J Roentgenol 168.1 (January 1997): 33-38.
PMID
8976915
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
168
Issue
1
Publish Date
1997
Start Page
33
End Page
38
DOI
10.2214/ajr.168.1.8976915

Epithelial repair of the uterine cervix: assessment of morphologic features and correlations with cytologic diagnosis.

This study evaluates the morphologic features of squamous epithelial repair of the uterine cervix, a condition describing a state of regeneration, and compares them with the features of its two histologic mimics, squamous metaplasia and mild dysplasia. The materials examined were from 20 patients with a histologic diagnosis of repair, 42 with cervical biopsy specimens of acceptable quality obtained within 3 weeks of a cervical smear showing repair, and 20 each with squamous metaplasia or mild dysplasia. Specimens with repair disclosed distinctive morphologic characteristics. On low-power magnification, the stroma was chronically inflamed (100%), often floridly (55%). The nuclei were uniform with absent or minimal pleomorphism (90%). The chromatin was bland and evenly distributed (70%). Nucleoli of a bull's eye or macronucleolar appearance (45%) were easily found. Mildly dysplastic epithelium, unlike reparative epithelium, was infrequently associated with an intensely inflamed stroma (20%); its nuclei were pleomorphic (100%) and commonly displayed coarse chromatin (75%) and mitoses (60%). Metaplastic epithelium ws also infrequently associated with an intensely inflamed stroma (10%). Nuclear pleomorphism (10%) and mitotic figures were infrequent (10%), never atypical (0%), and always basally located. Most nuclei had nucleoli, but the majority were small (80%). This study indicates that most cases of repair, mild dysplasia, and metaplasia can be readily distinguished, although due to overlapping features, some cases are difficult to classify as shown by interobserver variability.

Authors
Yelverton, CL; Bentley, RC; Olenick, S; Krigman, HR; Johnston, WW; Robboy, SJ
MLA Citation
Yelverton, CL, Bentley, RC, Olenick, S, Krigman, HR, Johnston, WW, and Robboy, SJ. "Epithelial repair of the uterine cervix: assessment of morphologic features and correlations with cytologic diagnosis." Int J Gynecol Pathol 15.4 (October 1996): 338-344.
PMID
8886881
Source
pubmed
Published In
International Journal of Gynecological Pathology
Volume
15
Issue
4
Publish Date
1996
Start Page
338
End Page
344

Prospective correlation of cervicovaginal cytologic and histologic specimens.

An effective, prospective, computer-guided method of correlation is reported. The mechanism for identification of cases, comparison of diagnoses, and reconciliation of discrepancies are explained. The results are similar to prior, retrospective, correlation studies. The benefits specific to this unique prospective approach include optimal capture of cases for correlation, minimization of errors before diagnoses are released to clinicians and patients, and internal standardization of diagnostic criteria. Three thousand four hundred and four consecutive paired cervicovaginal cytologies and biopsies were accessioned at the Pathology Department of Duke University Medical Center over a 43-month period. Of these, 481 paired cases (14%) had discordant diagnoses, defined as differing more than one degree of dysplasia or as dysplasia or carcinoma identified by only one modality. Additional evaluation reconciled the diagnostic differences in 35 cases. Eighteen initial diagnostic differences arose from cytologic screening errors, 16 from interpretive errors by staff pathologists, and one from superficial initial histologic sections. The remaining 446 discordances were attributed to sampling differences. The cytologic smear contained the diagnostic lesion in 40% of the cases and the biopsy the remainder, emphasizing the utility of pairing these sampling techniques in patients at risk for dysplasia.

Authors
Ibrahim, SN; Krigman, HR; Coogan, AC; Wax, TD; Dodd, LG; Bentley, RC; Robboy, SJ; Johnston, WW
MLA Citation
Ibrahim, SN, Krigman, HR, Coogan, AC, Wax, TD, Dodd, LG, Bentley, RC, Robboy, SJ, and Johnston, WW. "Prospective correlation of cervicovaginal cytologic and histologic specimens." Am J Clin Pathol 106.3 (September 1996): 319-324.
PMID
8816588
Source
pubmed
Published In
American Journal of Clinical Pathology
Volume
106
Issue
3
Publish Date
1996
Start Page
319
End Page
324

M6P/IGF2 receptor: a candidate breast tumor suppressor gene.

The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2r) functions in the activation of TGFbeta, a potent growth inhibitor for most cell types, the degradation of the mitogen, IGF2, and the intracellular trafficking of lysosomal enzymes. We have found its expression to be significantly reduced in both rat and human hepatocellular carcinomas (HCCs) and recently reported loss of heterozygosity (LOH) at this locus with mutations in the remaining allele in human liver tumors. Using the polymerase chain reaction, we utilized two polymorphisms in the 3' untranslated region of M6P/IGF2r to screen breast tumors for LOH. Forty of 62 (65%) patients were informative (heterozygous) and 12/40 (30%) breast tumors had LOH; 5/19 (26%) carcinomas in situ (CIS) and 7/21 (33%) invasive carcinomas. To investigate the early molecular genetic events in breast carcinogenesis, we screened the CIS with LOH for mutations. In 2/5 (40%) of these tumors, missense mutations were found in the remaining allele that gave rise to significant amino acid substitutions. These findings provide evidence that M6P/IGF2r allelic loss is an early event in the etiology of breast cancer, that this gene functions as a tumor suppressor gene in the breast.

Authors
Hankins, GR; De Souza, AT; Bentley, RC; Patel, MR; Marks, JR; Iglehart, JD; Jirtle, RL
MLA Citation
Hankins, GR, De Souza, AT, Bentley, RC, Patel, MR, Marks, JR, Iglehart, JD, and Jirtle, RL. "M6P/IGF2 receptor: a candidate breast tumor suppressor gene." Oncogene 12.9 (May 2, 1996): 2003-2009.
PMID
8649861
Source
pubmed
Published In
Oncogene: Including Oncogene Reviews
Volume
12
Issue
9
Publish Date
1996
Start Page
2003
End Page
2009

Production and characterization of two ependymoma xenografts.

Childhood ependymomas exhibit epidemiologic, anatomic, histologic, and biologic features and distinguish them from other gliomas. Because of their propensity to grow in functionally sensitive regions of the brain, adequate tumor sampling for basic and therapeutic research is limited. We have established xenografts in both subcutaneous and intracranial nude mouse systems (D528 EP-X, D612 EP-X) from the ependymomas of two nonrelated children. Median subcutaneous growth rates (reported in days to grow from 200 mm3 to 1000 mm3) are 82 days for D528 EP-X (n = 10) and 50 days for D612 EP-X (n = 10). D528 EP-X grows intracranially with a median postimplantation survival of 85 days (n = 10); D612 EP produces a median postimplantation survival of 72.5 days (n = 10). Both xenografts grow as well-formed masses with no evidence of infiltration into either brain or subcutaneous tissues. While perivascular pseudopalisading is found in both xenografts, true ependymal rosette formation is absent. Ultrastructurally, neither xenograft exhibits cilia, but both produce abundant intermediate filaments. By light microscopy, the neoplastic cells are immunoreactive for the intermediate filaments glial fibrillary acidic protein, vimentin, and nestin. Karyotypically D528 EP exhibits 46,XX,del(6)(q22q26)/46,XX while D612 EP exhibits 50,XX, +X,t(1;8)(p11;q11),t(1;8)(p11;q11), +1,-4, der(5)t(4;5)(q12;q35), +der(5)t(4;5)(q12;q35),-6, +9, +9,-16, +der(17)t(6;17)(p11;p11), +mar. Restriction fragment length polymorphism studies comparing the primary brain tumor tissue from each patient against multiple passages of the resulting xenografts confirm the origin of both xenografts. These xenografts represent models on which future studies into the oncogenesis, progression and therapy of ependymomas can be performed.

Authors
McLendon, RE; Fung, KM; Bentley, RC; Ahmed Rasheed, BK; Trojanowski, JQ; Bigner, SH; Bigner, DD; Friedman, HS
MLA Citation
McLendon, RE, Fung, KM, Bentley, RC, Ahmed Rasheed, BK, Trojanowski, JQ, Bigner, SH, Bigner, DD, and Friedman, HS. "Production and characterization of two ependymoma xenografts." J Neuropathol Exp Neurol 55.5 (May 1996): 540-548.
PMID
8627345
Source
pubmed
Published In
Journal of Neuropathology and Experimental Neurology
Volume
55
Issue
5
Publish Date
1996
Start Page
540
End Page
548

Gastric graft-versus-host disease: A coded histopathologic study

Authors
Washington, K; Bentley, RC; Olson, JF; Krigman, HR
MLA Citation
Washington, K, Bentley, RC, Olson, JF, and Krigman, HR. "Gastric graft-versus-host disease: A coded histopathologic study." LABORATORY INVESTIGATION 74.1 (January 1996): 383-383.
Source
wos-lite
Published In
Laboratory Investigation
Volume
74
Issue
1
Publish Date
1996
Start Page
383
End Page
383

Microcalcifications as elastic scatterers under ultrasound: implications for medical imaging

Microcalcifications are small crystals of calcium phosphates which form in human tissue through a number of mechanisms. The size, morphology, and distribution of microcalcifications (MCs) are important indicators in the mammographic screening for and diagnosis of various carcinomas in the breast. Current ultrasound methodology is not considered reliable at detecting MCs in the size range of clinical interest. The authors are investigating the imaging of MCs under ultrasound in the interest of extending the capabilities of ultrasound. We present an analysis of the acoustic properties of MCs modeled as elastic spheres which considers the predicted complex spectra and spatial coherence of echoes from MCs. We compare the findings of the model to actual echoes from suspected MCs in vivo, and discuss the implications of these findings for medical imaging. We also present preliminary in vivo measurements of phase aberration and the backscatter coefficient of breast tissue, and discuss the ramifications of these results for MC visualization.

Authors
Anderson, ME; Trahey, GE; Soo, MS; Bentley, RC
MLA Citation
Anderson, ME, Trahey, GE, Soo, MS, and Bentley, RC. "Microcalcifications as elastic scatterers under ultrasound: implications for medical imaging." Proceedings of the IEEE Ultrasonics Symposium 2 (1996): 1463-1467.
Source
scival
Published In
Proceedings of the IEEE Ultrasonics Symposium
Volume
2
Publish Date
1996
Start Page
1463
End Page
1467

Endometrioid carcinoma of the endometrium with sertoliform differentiation.

Ovarian endometrioid tumors with areas mimicking sex cord-stromal tumors are well documented in the literature, but it is unclear whether a similar tumor occurs in the endometrium. We report here a patient with an endometrial endometrioid adenocarcinoma resembling a Sertoli cell tumor. Immunohistochemical and ultrastructural investigations proved it was an adenocarcinoma rather than a true sex cord-stromal tumor. The features of the endometrial tumor were similar to those described in ovarian endometrioid tumors mimicking sex cord-stromal tumors and we compare them to true sex cord-stromal cell tumors. This case confirms that endometrioid adenocarcinoma with sertoliform differentiation can arise in the endometrium as well as in the ovary.

Authors
Usadi, RS; Bentley, RC
MLA Citation
Usadi, RS, and Bentley, RC. "Endometrioid carcinoma of the endometrium with sertoliform differentiation." Int J Gynecol Pathol 14.4 (October 1995): 360-364.
PMID
8598340
Source
pubmed
Published In
International Journal of Gynecological Pathology
Volume
14
Issue
4
Publish Date
1995
Start Page
360
End Page
364

Anaplastic renal cell carcinoma following neuroblastoma.

Renal cell carcinoma is unusual in children. We report a case of anaplastic renal cell carcinoma arising in a 7-year-old girl following treatment for Stage III neuroblastoma. The renal cell carcinoma has unusual histologic and ultrastructural features, which are discussed. The case is further unusual in that few children with advanced stage neuroblastoma survive long enough to develop second malignant neoplasms.

Authors
Krigman, HR; Bentley, RC; Strickland, DK; Miller, CR; Dehner, LP; Washington, K
MLA Citation
Krigman, HR, Bentley, RC, Strickland, DK, Miller, CR, Dehner, LP, and Washington, K. "Anaplastic renal cell carcinoma following neuroblastoma." Med Pediatr Oncol 25.1 (July 1995): 52-59. (Review)
PMID
7753003
Source
pubmed
Published In
Pediatric Blood and Cancer
Volume
25
Issue
1
Publish Date
1995
Start Page
52
End Page
59

Villoglandular adenocarcinoma of the cervix: a case report.

BACKGROUND: Villoglandular adenocarcinoma of the cervix is a rare neoplasm associated with a favorable outcome and has not been described as a complication of pregnancy. CASE: A gravida at 20 weeks' gestation was found to have a bulky stage-IB adenocarcinoma of the cervix. She was delivered at 32 weeks' gestation by cesarean, then a radical hysterectomy and pelvic and periaortic lymphadenectomies were performed. Pathology revealed a deeply invasive, grade 1 villoglandular adenocarcinoma confined to the cervix. The patient remains free of disease at 14 months follow-up. CONCLUSION: Villoglandular adenocarcinoma of the cervix has a favorable prognosis and can be managed conservatively, even when complicated by pregnancy.

Authors
Hurteau, JA; Rodriguez, GC; Kay, HH; Bentley, RC; Clarke-Pearson, D
MLA Citation
Hurteau, JA, Rodriguez, GC, Kay, HH, Bentley, RC, and Clarke-Pearson, D. "Villoglandular adenocarcinoma of the cervix: a case report." Obstet Gynecol 85.5 Pt 2 (May 1995): 906-908.
PMID
7724158
Source
pubmed
Published In
Obstetrics & Gynecology (Elsevier)
Volume
85
Issue
5 Pt 2
Publish Date
1995
Start Page
906
End Page
908

Malignant transformation of the human endometrium is associated with overexpression of lactoferrin messenger RNA and protein.

In the mouse uterus, lactoferrin is a major estrogen-inducible uterine secretory protein, and its expression correlates directly with the period of peak epithelial cell proliferation. In this study, we examine the expression of lactoferrin mRNA and protein in human endometrium, endometrial hyperplasias, and adenocarcinomas using immunohistochemistry, Western immunoblotting, and Northern and in situ RNA hybridization techniques. Our results reveal that lactoferrin is expressed in normal cycling endometrium by a restricted number of glandular epithelial cells located deep in the zona basalis. Two thirds (8 of 12) of the endometrial adenocarcinomas examined overexpress lactoferrin. This tumor-associated increase in lactoferrin expression includes an elevation in the mRNA and protein of individual cells and an increase in the number of cells expressing the protein. In comparison, only 1 of the 10 endometrial hyperplasia specimens examined demonstrates an increase in lactoferrin. We also observe distinct cytoplasmic and nuclear immunostaining patterns under different fixation conditions in both normal and malignant epithelial cells, similar to those previously reported in the mouse reproductive tract. Serial sections of malignant specimens show a good correlation between the localization of lactoferrin mRNA and protein in individual epithelial cells by in situ RNA hybridization and immunohistochemistry. Although the degree of lactoferrin expression in the adenocarcinomas did not correlate with the tumor stage, grade, or depth of invasion in these 12 patients, there was a striking inverse correlation between the presence of progesterone receptors and lactoferrin in all 8 lactoferrin-positive adenocarcinomas. In summary, lactoferrin is expressed in a region of normal endometrium known as the zona basalis which is not shed with menstruation and is frequently overexpressed by progesterone receptor-negative cells in endometrial adenocarcinomas.

Authors
Walmer, DK; Padin, CJ; Wrona, MA; Healy, BE; Bentley, RC; Tsao, MS; Kohler, MF; McLachlan, JA; Gray, KD
MLA Citation
Walmer, DK, Padin, CJ, Wrona, MA, Healy, BE, Bentley, RC, Tsao, MS, Kohler, MF, McLachlan, JA, and Gray, KD. "Malignant transformation of the human endometrium is associated with overexpression of lactoferrin messenger RNA and protein." Cancer Res 55.5 (March 1, 1995): 1168-1175.
PMID
7867003
Source
pubmed
Published In
Cancer Research
Volume
55
Issue
5
Publish Date
1995
Start Page
1168
End Page
1175

Papillary carcinoma of the breast: imaging findings.

Papillary carcinoma is a rare malignant tumor of the breast for which the survival rate is better than for most breast carcinomas. Histologically, invasive and in situ forms occur; the in situ form can extend throughout a ductal system (intraductal) or can be confined within a cystic structure (intracystic). Invasive papillary carcinoma can spread from either of the in situ forms but spreads more commonly from the intracystic type. Many reports in the literature have failed to differentiate invasive from in situ papillary carcinomas; similarly, the different mammographic patterns of the two in situ forms of these lesions have not been delineated clearly. Our review of 16 new cases of papillary carcinoma showed a frequent correlation between the histologic types and the mammographic appearance. The intraductal in situ form usually was characterized by clustered microcalcifications. The intracystic in situ type was associated with well-circumscribed masses on mammograms; these masses often were complex on sonograms. The purpose of this essay is to illustrate the mammographic and sonographic features of the histologic varieties of papillary carcinoma. Color Doppler sonograms and MR images of intracystic and invasive tumors also are included.

Authors
Soo, MS; Williford, ME; Walsh, R; Bentley, RC; Kornguth, PJ
MLA Citation
Soo, MS, Williford, ME, Walsh, R, Bentley, RC, and Kornguth, PJ. "Papillary carcinoma of the breast: imaging findings." AJR Am J Roentgenol 164.2 (February 1995): 321-326.
PMID
7839962
Source
pubmed
Published In
AJR. American journal of roentgenology
Volume
164
Issue
2
Publish Date
1995
Start Page
321
End Page
326
DOI
10.2214/ajr.164.2.7839962

Borderline and malignant serous tumor arising in pelvic lymph nodes: evidence of origin in benign glandular inclusions.

This report describes two cases of malignant serous cancers with areas of borderline malignancy, which appear to have arisen within benign glandular inclusions of coelomic origin in pelvic or para-aortic lymph nodes. The patients were 44 and 62 years of age. In both cases the nodes contained benign glandular inclusions lined by a single layer of epithelium which resembled that of tubal epithelium. The location of the glandular epithelium varied from within the fat near the node to intracapsular, subcapsular, or interfollicular positions. The number of glands ranged from few to extensive. In both cases the glandular inclusions disclosed epithelial proliferations, ranging from minor degrees of stratification with formation of small papillae of atypical cells (borderline serous tumor) to almost solid tumor typical of serous cancer. In both cases, the borderline and cancerous tumors exhibited areas of transition which appeared to arise from benign glands. Although benign glandular inclusions of coelomic origin are well documented to occur in pelvic or para-aortic lymph nodes of 5-20% of women and have been considered to be of significance only because of the possibility of the misdiagnosis of cancer, it should now be recognized that the glandular inclusion cysts themselves can become neoplastic.

Authors
Prade, M; Spatz, A; Bentley, R; Duvillard, P; Bognel, C; Robboy, SJ
MLA Citation
Prade, M, Spatz, A, Bentley, R, Duvillard, P, Bognel, C, and Robboy, SJ. "Borderline and malignant serous tumor arising in pelvic lymph nodes: evidence of origin in benign glandular inclusions." Int J Gynecol Pathol 14.1 (January 1995): 87-91.
PMID
7883433
Source
pubmed
Published In
International Journal of Gynecological Pathology
Volume
14
Issue
1
Publish Date
1995
Start Page
87
End Page
91

Villoglandular adenocarcinoma of the cervix: A case report

Background: Villoglandular adenocarcinoma of the cervix is a rare neoplasm associated with a favorable outcome and has not been described as a complication of pregnancy. Case: A gravida at 20 weeks' gestation was found to have a bulky stage-IB adenocarcinoma of the cervix. She was delivered at 32 weeks' gestation by cesarean, then a radical hysterectomy and pelvic and periaortic lymphadenectomies were performed. Pathology revealed a deeply invasive, grade 1 villoglandular adenocarcinoma confined to the cervix. The patient remains free of disease at 14 months follow-up. Conclusion: Villoglandular adenocarcinoma of the cervix has a favorable prognosis and can be managed conservatively, even when complicated by pregnancy.

Authors
Hurteau, JA; Rodriguez, GC; Kay, HH; Bentley, RC; Clarke-Pearson, D
MLA Citation
Hurteau, JA, Rodriguez, GC, Kay, HH, Bentley, RC, and Clarke-Pearson, D. "Villoglandular adenocarcinoma of the cervix: A case report." Obstetrics and Gynecology 85.5 II SUPPL. (1995): 906-908.
Source
scival
Published In
Obstetrics and Gynecology
Volume
85
Issue
5 II SUPPL.
Publish Date
1995
Start Page
906
End Page
908
DOI
10.1016/0029-7844(94)00418-D

Evaluation of the ultrasonic detectability of microcalcifications

Microcalcifications are small crystals of calcium apatites which form in human tissue through a number of mechanisms. The size, morphology, and distribution of microcalcifications are important indicators in the mammographic screening for and diagnosis of various carcinomas in the breast. Though x-ray mammography is currently the only accepted method for detecting microcalcifications, its efficacy in this regard can be reduced in the presence of dense parenchyma. Current ultrasound scanners are not capable of detecting microcalcifications in the size range of clinical interest. We present methods for estimating the changes in microcalcification detection performance which result from changes in aperture geometry or the presence of an aberrator. We present an analysis of the relative efficacy of spatial compounding and synthetic receive aperture geometries in the detection of microcalcifications. We present a preliminary analysis estimating the impact of phase aberration on detection. We present registered high resolution ultrasound and digital spot mammography images of microcalcifications in excised breast carcinoma tissue.

Authors
Anderson, M; Soo, MS; Bentley, R; Trahey, G
MLA Citation
Anderson, M, Soo, MS, Bentley, R, and Trahey, G. "Evaluation of the ultrasonic detectability of microcalcifications." Proceedings of the IEEE Ultrasonics Symposium 2 (1995): 1161-1166.
Source
scival
Published In
Proceedings of the IEEE Ultrasonics Symposium
Volume
2
Publish Date
1995
Start Page
1161
End Page
1166

Pathology of epithelial ovarian tumors.

Authors
Krigman, H; Bentley, R; Robboy, SJ
MLA Citation
Krigman, H, Bentley, R, and Robboy, SJ. "Pathology of epithelial ovarian tumors." Clin Obstet Gynecol 37.2 (June 1994): 475-491. (Review)
PMID
8033455
Source
pubmed
Published In
Clinical Obstetrics and Gynecology
Volume
37
Issue
2
Publish Date
1994
Start Page
475
End Page
491

Multivariable analysis of DNA ploidy, p53, and HER-2/neu as prognostic factors in endometrial cancer.

BACKGROUND: Several molecular-genetic alterations in endometrial cancers, including aneuploidy and aberrant expression of p53 and HER-2/neu, have been associated with poor prognosis. To determine the importance of molecular-genetic factors relative to more traditional surgical-pathologic prognostic factors, a multivariable analysis was performed. METHODS: Immunohistochemical staining for p53, HER-2/neu, estrogen receptor, progesterone receptor, and epidermal growth factor receptor was performed on frozen sections from 100 primary endometrial cancers. DNA ploidy was determined using computerized image analysis of Feulgen-stained touch preparations. In addition, information regarding surgical-pathologic features of the cancers was obtained. Univariable analysis was performed followed by multivariable analysis using Cox's proportional hazards model to identify variables predictive of poor prognosis. RESULTS: With univariable analysis, race, histologic type, stage, grade, myometrial invasion, estrogen receptor, progesterone receptor, ploidy, p53 and HER-2/neu were predictive of the presence of persistent or recurrent disease. In the multivariable analysis, only International Federation of Gynecology and Obstetrics stage (P = 0.005), grade (P = 0.005), myometrial invasion (P = 0.024), and ploidy (P = 0.028) were significant. CONCLUSIONS: Among molecular-genetic prognostic factors, DNA ploidy was the most strongly predictive of persistent or recurrent disease.

Authors
Lukes, AS; Kohler, MF; Pieper, CF; Kerns, BJ; Bentley, R; Rodriguez, GC; Soper, JT; Clarke-Pearson, DL; Bast, RC; Berchuck, A
MLA Citation
Lukes, AS, Kohler, MF, Pieper, CF, Kerns, BJ, Bentley, R, Rodriguez, GC, Soper, JT, Clarke-Pearson, DL, Bast, RC, and Berchuck, A. "Multivariable analysis of DNA ploidy, p53, and HER-2/neu as prognostic factors in endometrial cancer." Cancer 73.9 (May 1, 1994): 2380-2385.
PMID
7909491
Source
pubmed
Published In
Cancer
Volume
73
Issue
9
Publish Date
1994
Start Page
2380
End Page
2385

Synoptic reports in gynecologic pathology.

Authors
Robboy, SJ; Bentley, RC; Krigman, H; Silverberg, SG; Norris, HJ; Zaino, RJ
MLA Citation
Robboy, SJ, Bentley, RC, Krigman, H, Silverberg, SG, Norris, HJ, and Zaino, RJ. "Synoptic reports in gynecologic pathology." Int J Gynecol Pathol 13.2 (April 1994): 161-174.
PMID
8005738
Source
pubmed
Published In
International Journal of Gynecological Pathology
Volume
13
Issue
2
Publish Date
1994
Start Page
161
End Page
174

Genotypic divergence precedes clinical dissemination in a case of synchronous bilateral B-cell malignant lymphoma of the testes.

Malignant lymphoma of the testis occurs bilaterally more often than any other tumor type. We report the case of a 62-year-old man who presented with synchronous, bilateral, testicular malignant lymphomas without clinical or radiologic evidence of extratesticular disease. The patient received no therapy other than bilateral orchiectomy and subsequently developed widespread disease 6 months later. Southern blot DNA analysis was performed on the initial orchiectomy samples for immunoglobulin (Ig) gene rearrangements. These genotypic analyses showed different clonal rearrangements in the Ig heavy chain JH region but identical clonal rearrangements in the Ig light chain C Kappa region. To our knowledge this is the first genotypic demonstration of a common clonal origin in synchronous, bilateral, testicular malignant lymphomas. We interpret these findings as molecular evidence that the patient's malignant lymphoma was already disseminated at initial presentation, although it was clinically undetectable at that time.

Authors
Bentley, RC; Devlin, B; Kaufman, RE; Borowitz, M; Ratech, H
MLA Citation
Bentley, RC, Devlin, B, Kaufman, RE, Borowitz, M, and Ratech, H. "Genotypic divergence precedes clinical dissemination in a case of synchronous bilateral B-cell malignant lymphoma of the testes." Hum Pathol 24.6 (June 1993): 675-678.
PMID
8505044
Source
pubmed
Published In
Human Pathology
Volume
24
Issue
6
Publish Date
1993
Start Page
675
End Page
678

Recognition of U1 and U2 small nuclear RNAs can be altered by a 5-amino-acid segment in the U2 small nuclear ribonucleoprotein particle (snRNP) B" protein and through interactions with U2 snRNP-A' protein.

We have investigated the sequence elements influencing RNA recognition in two closely related small nuclear ribonucleoprotein particle (snRNP) proteins, U1 snRNP-A and U2 snRNP-B". A 5-amino-acid segment in the RNA-binding domain of the U2 snRNP-B" protein was found to confer U2 RNA recognition when substituted into the corresponding position in the U1 snRNP-A protein. In addition, B", but not A, was found to require the U2 snRNP-A' protein as an accessory factor for high-affinity binding to U2 RNA. The pentamer segment in B" that conferred U2 RNA recognition was not sufficient to allow the A' enhancement of U2 RNA binding by B", thus implicating other sequences in this protein-protein interaction. Sequence elements involved in these interactions have been localized to variable loops of the RNA-binding domain as determined by nuclear magnetic resonance spectroscopy (D. Hoffman, C.C. Query, B. Golden, S.W. White, and J.D. Keene, Proc. Natl. Acad. Sci. USA, in press). These findings suggest a role for accessory proteins in the formation of RNP complexes and pinpoint amino acid sequences that affect the specificity of RNA recognition in two members of a large family of proteins involved in RNA processing.

Authors
Bentley, RC; Keene, JD
MLA Citation
Bentley, RC, and Keene, JD. "Recognition of U1 and U2 small nuclear RNAs can be altered by a 5-amino-acid segment in the U2 small nuclear ribonucleoprotein particle (snRNP) B" protein and through interactions with U2 snRNP-A' protein." Mol Cell Biol 11.4 (April 1991): 1829-1839.
PMID
1826042
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
11
Issue
4
Publish Date
1991
Start Page
1829
End Page
1839

Expression of autoantibodies to recombinant (U1) RNP-associated 70K antigen in systemic lupus erythematosus.

To determine the specificity of antibodies to the (U1) ribonucleoprotein antigen in systemic lupus erythematosus (SLE), patient sera were tested for binding to a recombinant human 70K antigen. By solid-phase immunoassay, we detected anti-70K reactivity in sera from 31 of 96 patients with systemic lupus erythematosus (SLE), demonstrating that anti-70K antibodies may occur in patients with SLE as well as other clinical diagnoses. In sequential sera from 2 of these patients, we found that anti-70K binding varied dramatically over the course of disease. The changes in anti-70K antibody levels did not correlate with clinical events nor evolving antibody reactivity with the Sm-specific antigens.

Authors
St Clair, EW; Query, CC; Bentley, R; Keene, JD; Polisson, RP; Allen, NB; Caldwell, DS; Rice, JR; Cox, C; Pisetsky, DS
MLA Citation
St Clair, EW, Query, CC, Bentley, R, Keene, JD, Polisson, RP, Allen, NB, Caldwell, DS, Rice, JR, Cox, C, and Pisetsky, DS. "Expression of autoantibodies to recombinant (U1) RNP-associated 70K antigen in systemic lupus erythematosus." Clin Immunol Immunopathol 54.2 (February 1990): 266-280.
PMID
2104788
Source
pubmed
Published In
Clinical Immunology and Immunopathology
Volume
54
Issue
2
Publish Date
1990
Start Page
266
End Page
280

A specific 31-nucleotide domain of U1 RNA directly interacts with the 70K small nuclear ribonucleoprotein component.

We have defined the nucleotide sequence of a protein-binding domain within U1 RNA that specifically recognizes and binds both to a U1 small nuclear ribonucleoprotein component (the 70K protein) and to the previously defined RNA-binding domain of the 70K protein. We have investigated direct interactions between purified U1 RNA and 70K protein by reconstitution in vitro. Thirty-one nucleotides of U1 RNA, corresponding to stem-loop I, were required for this interaction. Nucleotides at the 5' end of U1 RNA that are involved in base pairing with the 5' splice site of pre-mRNA were not required for binding. In contrast to other reports, these findings demonstrate that a specific domain of U1 RNA can bind directly to the 70K protein independently of any other snRNP-associated proteins.

Authors
Query, CC; Bentley, RC; Keene, JD
MLA Citation
Query, CC, Bentley, RC, and Keene, JD. "A specific 31-nucleotide domain of U1 RNA directly interacts with the 70K small nuclear ribonucleoprotein component." Mol Cell Biol 9.11 (November 1989): 4872-4881.
PMID
2532301
Source
pubmed
Published In
Molecular and Cellular Biology
Volume
9
Issue
11
Publish Date
1989
Start Page
4872
End Page
4881

A common RNA recognition motif identified within a defined U1 RNA binding domain of the 70K U1 snRNP protein.

We have defined the RNA binding domain of the 70K protein component of the U1 small nuclear ribonucleoprotein to a region of 111 amino acids. This domain encompasses an octamer sequence that has been observed in other proteins associated with RNA, but has not previously been shown to bind directly to a specific RNA sequence. Within the U1 RNA binding domain, an 80 amino acid consensus sequence that is conserved in many presumed RNA binding proteins was discerned. This sequence pattern appears to represent an RNA recognition motif (RRM) characteristic of a distinct family of proteins. By site-directed mutagenesis, we determined that the 70K protein consists of 437 amino acids (52 kd), and found that its aberrant electrophoretic migration is due to a carboxy-terminal charged domain structurally similar to two Drosophila proteins (su(wa) and tra) that may regulate alternative pre-messenger RNA splicing.

Authors
Query, CC; Bentley, RC; Keene, JD
MLA Citation
Query, CC, Bentley, RC, and Keene, JD. "A common RNA recognition motif identified within a defined U1 RNA binding domain of the 70K U1 snRNP protein." Cell 57.1 (April 7, 1989): 89-101.
PMID
2467746
Source
pubmed
Published In
Cell
Volume
57
Issue
1
Publish Date
1989
Start Page
89
End Page
101

Pre-proglucagon messenger ribonucleic acid: nucleotide and encoded amino acid sequences of the rat pancreatic complementary deoxyribonucleic acid.

Glucagon, a pancreatic peptide hormone of 29 amino acids that regulates carbohydrate, fat, and protein metabolism, is one of a family of structurally similar regulatory peptides which include GH-releasing hormone, vasoactive intestinal peptide, secretin, and gastric inhibitory peptide. The synthesis of glucagon involves its specific proteolytic cleavage from preproglucagon, a large polyprotein precursor. To facilitate analyses of the cellular processing of pre-proglucagon and to begin studies of the regulation of glucagon gene expression in the rat, we have cloned and sequenced two cDNAs derived from rat neonatal pancreas. The cDNAs represent close to the entire transcriptional sequence of the glucagon gene and encode a pre-proglucagon of 180 amino acids. The coding region of pre-proglucagon contains, in addition to the sequence of glucagon, the sequences of two peptide domains that are related in their structures to glucagon. Glucagon and the two glucagon-like peptides are flanked in the precursor by pairs of basic amino acids characteristic of the sites that are cleaved during the posttranslational processing of pro-hormones. Northern blot analyses indicate the presence of a single mRNA of 1400 +/- 100 nucleotides in the rat pancreas, and results of Southern blotting of rat liver genomic DNA are consistent with the existence of a single chromosomal gene. Comparisons of the nucleotide sequence of the rat pre-proglucagon cDNA with those of the two pre-proglucagons of the anglerfish pancreas encoded by two separate genes indicate that the pre-proglucagon genes probably evolved by intragenic duplications of a DNA segment corresponding to the coding sequences of glucagon and the glucagon-like peptides.

Authors
Heinrich, G; Gros, P; Lund, PK; Bentley, RC; Habener, JF
MLA Citation
Heinrich, G, Gros, P, Lund, PK, Bentley, RC, and Habener, JF. "Pre-proglucagon messenger ribonucleic acid: nucleotide and encoded amino acid sequences of the rat pancreatic complementary deoxyribonucleic acid." Endocrinology 115.6 (December 1984): 2176-2181.
PMID
6548696
Source
pubmed
Published In
Endocrinology
Volume
115
Issue
6
Publish Date
1984
Start Page
2176
End Page
2181
DOI
10.1210/endo-115-6-2176
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