help button home button Am J Pathol Angiogenesis Meeting
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Singer, G.
Right arrow Articles by Shih, I.-M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Singer, G.
Right arrow Articles by Shih, I.-M.
(American Journal of Pathology. 2002;160:1223-1228.)
© 2002 American Society for Investigative Pathology


Short Communication

Diverse Tumorigenic Pathways in Ovarian Serous Carcinoma

Gad Singer*, Robert J. Kurman*{dagger}, Hsueh-Wei Chang*, Sarah K.R. Cho* and Ie-Ming Shih*

From the Departments of Pathology* andGynecology and Obstetrics,{dagger} The Johns HopkinsUniversity School of Medicine, Baltimore, Maryland

This study was undertaken to analyze genetic alterations in 108 sporadic serous ovarian neoplasms to elucidate ovarian serous carcinogenesis. Our results demonstrate that K-ras mutations occur in approximately 50% of serous borderline tumors (SBTs), non-invasive micropapillary serous carcinomas (MPSCs), and invasive micropapillary serous carcinomas, which represent a morphological continuum of tumor progression. Moreover, progressive increase in the degree of allelic imbalance of chromosomes 1p, 5q, 8p, 18q, 22q, and Xp was observed comparing serous borderline tumors to noninvasive and invasive micropapillary serous carcinomas. In contrast, high-grade (conventional serous carcinoma) tumors contained wild-type K-ras in all 23 cases studied and a high frequency of allelic imbalance even in small (early) primary tumors similar to that found in advanced stage tumors. Based on these findings, we propose a dualistic model for ovarian serous carcinogenesis. One pathway involves a stepwise progression from SBT to noninvasive and then invasive MPSC. The other pathway is characterized by rapid progression from the ovarian surface epithelium or inclusion cysts to a conventional (high-grade) serous carcinoma.





This article has been cited by other articles:


Home page
Clin. Cancer Res.Home page
R. W. Tothill, A. V. Tinker, J. George, R. Brown, S. B. Fox, S. Lade, D. S. Johnson, M. K. Trivett, D. Etemadmoghadam, B. Locandro, et al.
Novel Molecular Subtypes of Serous and Endometrioid Ovarian Cancer Linked to Clinical Outcome
Clin. Cancer Res., August 15, 2008; 14(16): 5198 - 5208.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
A. A. Tone, H. Begley, M. Sharma, J. Murphy, B. Rosen, T. J. Brown, and P. A. Shaw
Gene Expression Profiles of Luteal Phase Fallopian Tube Epithelium from BRCA Mutation Carriers Resemble High-Grade Serous Carcinoma
Clin. Cancer Res., July 1, 2008; 14(13): 4067 - 4078.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Pathol.Home page
K Miller, J H Price, S P Dobbs, R H McClelland, K Kennedy, and W G McCluggage
An immunohistochemical and morphological analysis of post-chemotherapy ovarian carcinoma
J. Clin. Pathol., May 1, 2008; 61(5): 652 - 657.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Pathol.Home page
W G McCluggage
My approach to and thoughts on the typing of ovarian carcinomas
J. Clin. Pathol., February 1, 2008; 61(2): 152 - 163.
[Abstract] [Full Text] [PDF]


Home page
J. Clin. Pathol.Home page
S. Stadlmann, U. Gueth, E. Wight, L. A Kunz-Schughart, A. Hartmann, and G. Singer
Expression of peroxisome proliferator activated receptor {gamma} and cyclo-oxygenase 2 in primary and recurrent ovarian carcinoma
J. Clin. Pathol., March 1, 2007; 60(3): 307 - 310.
[Abstract] [Full Text] [PDF]


Home page
Obstet GynecolHome page
D. M. Gershenson, C. C. Sun, K. H. Lu, R. L. Coleman, A. K. Sood, A. Malpica, M. T. Deavers, E. G. Silva, and D. C. Bodurka
Clinical Behavior of Stage II-IV Low-Grade Serous Carcinoma of the Ovary
Obstet. Gynecol., August 1, 2006; 108(2): 361 - 368.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
S. Miotti, A. Tomassetti, I. Facetti, E. Sanna, V. Berno, and S. Canevari
Simultaneous Expression of Caveolin-1 and E-Cadherin in Ovarian Carcinoma Cells Stabilizes Adherens Junctions through Inhibition of src-Related Kinases
Am. J. Pathol., November 1, 2005; 167(5): 1411 - 1427.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
I.-M. Shih and R. J. Kurman
Molecular Pathogenesis of Ovarian Borderline Tumors: New Insights and Old Challenges
Clin. Cancer Res., October 15, 2005; 11(20): 7273 - 7279.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
R. T. Marquez, K. A. Baggerly, A. P. Patterson, J. Liu, R. Broaddus, M. Frumovitz, E. N. Atkinson, D. I. Smith, L. Hartmann, D. Fishman, et al.
Patterns of Gene Expression in Different Histotypes of Epithelial Ovarian Cancer Correlate with Those in Normal Fallopian Tube, Endometrium, and Colon
Clin. Cancer Res., September 1, 2005; 11(17): 6116 - 6126.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
P. B. Makarla, M. H. Saboorian, R. Ashfaq, K. O. Toyooka, S. Toyooka, J. D. Minna, A. F. Gazdar, and J. O. Schorge
Promoter Hypermethylation Profile of Ovarian Epithelial Neoplasms
Clin. Cancer Res., August 1, 2005; 11(15): 5365 - 5369.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
G. Pohl, C.-L. Ho, R. J. Kurman, R. Bristow, T.-L. Wang, and I.-M. Shih
Inactivation of the Mitogen-Activated Protein Kinase Pathway as a Potential Target-Based Therapy in Ovarian Serous Tumors with KRAS or BRAF Mutations
Cancer Res., March 1, 2005; 65(5): 1994 - 2000.
[Abstract] [Full Text] [PDF]


Home page
Cancer Res.Home page
Y.-C. Chen, G. Pohl, T.-L. Wang, P. J. Morin, B. Risberg, G. B. Kristensen, A. Yu, B. Davidson, and I.-M. Shih
Apolipoprotein E Is Required for Cell Proliferation and Survival in Ovarian Cancer
Cancer Res., January 1, 2005; 65(1): 331 - 337.
[Abstract] [Full Text] [PDF]


Home page
NEJMHome page
R. T. Penson, D. Sahani, and D. A. Bell
Case 37-2004 - A 52-Year-Old Woman with Postmenopausal Bleeding and a Cystic Ovarian Mass
N. Engl. J. Med., December 9, 2004; 351(24): 2531 - 2538.
[Full Text] [PDF]


Home page
Cancer Res.Home page
C.-L. Ho, R. J. Kurman, R. Dehari, T.-L. Wang, and I.-M. Shih
Mutations of BRAF and KRAS Precede the Development of Ovarian Serous Borderline Tumors
Cancer Res., October 1, 2004; 64(19): 6915 - 6918.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
C.-Y. Hsu, R. Bristow, M. S. Cha, B. G. Wang, C.-L. Ho, R. J. Kurman, T.-L. Wang, and I.-M. Shih
Characterization of Active Mitogen-Activated Protein Kinase in Ovarian Serous Carcinomas
Clin. Cancer Res., October 1, 2004; 10(19): 6432 - 6436.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
V. A. Heinzelmann-Schwarz, M. Gardiner-Garden, S. M. Henshall, J. Scurry, R. A. Scolyer, M. J. Davies, M. Heinzelmann, L. H. Kalish, A. Bali, J. G. Kench, et al.
Overexpression of the Cell Adhesion Molecules DDR1, Claudin 3, and Ep-CAM in Metaplastic Ovarian Epithelium and Ovarian Cancer
Clin. Cancer Res., July 1, 2004; 10(13): 4427 - 4436.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
I.-M. Shih and R. J. Kurman
Ovarian Tumorigenesis: A Proposed Model Based on Morphological and Molecular Genetic Analysis
Am. J. Pathol., May 1, 2004; 164(5): 1511 - 1518.
[Abstract] [Full Text] [PDF]


Home page
JCOHome page
R. Hogg and M. Friedlander
Biology of Epithelial Ovarian Cancer: Implications for Screening Women at High Genetic Risk
J. Clin. Oncol., April 1, 2004; 22(7): 1315 - 1327.
[Abstract] [Full Text] [PDF]


Home page
Am J EpidemiolHome page
K.-H. Tung, M. T. Goodman, A. H. Wu, K. McDuffie, L. R. Wilkens, L. N. Kolonel, A. M. Y. Nomura, K. Y. Terada, M. E. Carney, and L. H. Sobin
Reproductive Factors and Epithelial Ovarian Cancer Risk by Histologic Type:A Multiethnic Case-Control Study
Am. J. Epidemiol., October 1, 2003; 158(7): 629 - 638.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
G. Singer, R. Oldt III, Y. Cohen, B. G. Wang, D. Sidransky, R. J. Kurman, and I.-M. Shih
Mutations in BRAF and KRAS Characterize the Development of Low-Grade Ovarian Serous Carcinoma
J Natl Cancer Inst, March 19, 2003; 95(6): 484 - 486.
[Abstract] [Full Text] [PDF]


Home page
JNCI J Natl Cancer InstHome page
H.-W. Chang, S. M. Lee, S. N. Goodman, G. Singer, S. K. R. Cho, L. J. Sokoll, F. J. Montz, R. Roden, Z. Zhang, D. W. Chan, et al.
Assessment of Plasma DNA Levels, Allelic Imbalance, and CA 125 as Diagnostic Tests for Cancer
J Natl Cancer Inst, November 20, 2002; 94(22): 1697 - 1703.
[Abstract] [Full Text] [PDF]


Home page
Cancer Epidemiol. Biomarkers Prev.Home page
H.-W. Chang, C.-Y. Yen, S.-Y. Liu, G. Singer, and I.-M. Shih
Genotype Analysis Using Human Hair Shaft
Cancer Epidemiol. Biomarkers Prev., September 1, 2002; 11(9): 925 - 929.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
H.-W. Chang, S. Z. Ali, S. K. R. Cho, R. J. Kurman, and I.-M. Shih
Detection of Allelic Imbalance in Ascitic Supernatant by Digital Single Nucleotide Polymorphism Analysis
Clin. Cancer Res., August 1, 2002; 8(8): 2580 - 2585.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2002 by the American Society for Investigative Pathology.