Originally published as JCO Early Release 10.1200/JCO.2006.07.9970 on January 14 2008

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Early Events in the Pathogenesis of Epithelial Ovarian Cancer

Charles N. Landen, Jr, Michael J. Birrer, Anil K. Sood

From the Department of Gynecologic Oncology and the Department of Cancer Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX; and the Center for Cancer Research, National Cancer Institute, Bethesda, MD

Corresponding author: Anil K. Sood, MD, Professor, Departments of Gynecologic Oncology and Cancer Biology, University of Texas M.D. Anderson Cancer Center, 1155 Herman Pressler, Unit 1362, Houston, TX 77030; e-mail: asood{at}mdanderson.org

Ovarian carcinogenesis, as in most cancers, involves multiple genetic alterations. A great deal has been learned about proteins and pathways important in the early stages of malignant transformation and metastasis, as derived from studies of individual tumors, microarray data, animal models, and inherited disorders that confer susceptibility. However, a full understanding of the earliest recognizable events in epithelial ovarian carcinogenesis is limited by the lack of a well-defined premalignant state common to all ovarian subtypes and by the paucity of data from early-stage cancers. Evidence suggests that ovarian cancers can progress both through a stepwise mutation process (low-grade pathway) and through greater genetic instability that leads to rapid metastasis without an identifiable precursor lesion (high-grade pathway). In this review, we discuss many of the genetic and molecular disorders in each key process that is altered in cancer cells, and we present a model of ovarian pathogenesis that incorporates the role of tumor cell mutations and factors in the host microenvironment important to tumor initiation and progression.

published online ahead of print at www.jco.org on January 14, 2008.

Supported in part by the Reproductive Scientist Development Program through NIH Grant No. 5K12HD00849 and the Ovarian Cancer Research Fund (C.N.L.); Grants No. CA 11079301 and CA 10929801 from the National Institutes of Health (A.K.S.); Grant No. P50 CA083639 from the M.D. Anderson Cancer Center Ovarian Cancer Specialized Program of Research Excellence; a Program Project Development Grant from the Ovarian Cancer Research Fund Inc; the Marcus Foundation (A.K.S.); and the Intramural Research Program of the National Institutes of Health, National Cancer Institute (M.J.B.).

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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