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Critical molecular abnormalities in high-grade serous carcinoma of the ovary

Published online by Cambridge University Press:  01 August 2008

Martin Köbel
Affiliation:
Genetic Pathology Evaluation Centre of the Prostate Research Centre, Department of Pathology, Vancouver General Hospital and British Columbia Cancer Agency, Vancouver BC, Canada. Institute of Pathology, Charité Hospital, Berlin 10117, Germany.
David Huntsman
Affiliation:
Genetic Pathology Evaluation Centre of the Prostate Research Centre, Department of Pathology, Vancouver General Hospital and British Columbia Cancer Agency, Vancouver BC, Canada.
C. Blake Gilks*
Affiliation:
Genetic Pathology Evaluation Centre of the Prostate Research Centre, Department of Pathology, Vancouver General Hospital and British Columbia Cancer Agency, Vancouver BC, Canada.
*
*Corresponding author: C. Blake Gilks, Department of Pathology, Room 1207 1st floor JPPN, Vancouver General Hospital, 855 West 12th Ave, Vancouver, BC, Canada, V5Z 1M9. Tel.: +1 (604) 875 4901; Fax: +1 (604) 875 4797; E-mail: Blake.Gilks@vch.ca

Abstract

Ovarian carcinomas show more morphological heterogeneity than adenocarcinomas of any other body site. It has recently become clear that the morphologically defined subtypes of ovarian carcinoma are distinct diseases, with different risk factors, molecular events during oncogenesis, likelihood of spread, responses to chemotherapy, and outcomes. This review focuses on molecular abnormalities (in genes expressing BRCA1/2, TP53 and RB1/CCND1/CDKN2A/E2F) found in high-grade serous carcinomas of the ovary, which account for most ovarian cancer deaths. These highly aggressive but chemosensitive tumours are associated with perturbation of molecular pathways leading to genomic instability and extreme mutability and present unique challenges in oncological research and practice.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2008

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References

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Further reading, resources and contacts

For examples of the morphological appearance of different ovarian carcinoma subtypes see:

Naora, H. (2007) The heterogeneity of epithelial ovarian cancers: reconciling old and new paradigms. Expert Rev Mol Med 9, 1-12Google Scholar
Barton, C.A. et al. (2008) DNA methylation changes in ovarian cancer: implications for early diagnosis, prognosis and treatment. Gynecol Oncol 109, 129-139Google Scholar
Tan, D.S. et al. (2006) Mechanisms of transcoelomic metastasis in ovarian cancer. Lancet Oncol 7, 925-934Google Scholar
Hu, Y.L. et al. (2003) Dual mechanisms for lysophosphatidic acid stimulation of human ovarian carcinoma cells. J Natl Cancer Inst 95, 733-740Google Scholar
Sherman-Baust, C.A. et al. (2003) Remodeling of the extracellular matrix through overexpression of collagen VI contributes to cisplatin resistance in ovarian cancer cells. Cancer Cell 3, 377-386CrossRefGoogle ScholarPubMed
http://spectrum.med.ubc.ca/pathology/ (username: ovcare; password: diamond. Click on ‘List all Digital Slides’).Google Scholar
Naora, H. (2007) The heterogeneity of epithelial ovarian cancers: reconciling old and new paradigms. Expert Rev Mol Med 9, 1-12Google Scholar
Barton, C.A. et al. (2008) DNA methylation changes in ovarian cancer: implications for early diagnosis, prognosis and treatment. Gynecol Oncol 109, 129-139Google Scholar
Tan, D.S. et al. (2006) Mechanisms of transcoelomic metastasis in ovarian cancer. Lancet Oncol 7, 925-934Google Scholar
Hu, Y.L. et al. (2003) Dual mechanisms for lysophosphatidic acid stimulation of human ovarian carcinoma cells. J Natl Cancer Inst 95, 733-740Google Scholar
Sherman-Baust, C.A. et al. (2003) Remodeling of the extracellular matrix through overexpression of collagen VI contributes to cisplatin resistance in ovarian cancer cells. Cancer Cell 3, 377-386CrossRefGoogle ScholarPubMed
http://spectrum.med.ubc.ca/pathology/ (username: ovcare; password: diamond. Click on ‘List all Digital Slides’).Google Scholar