Originally published as JCO Early Release 10.1200/JCO.2008.18.1107 on October 14 2008

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New Insights Into the Pathogenesis of Serous Ovarian Cancer and Its Clinical Impact

Keren Levanon, Christopher Crum, Ronny Drapkin

From the Department of Medical Oncology, Dana-Farber Cancer Institute; and the Department of Pathology, Brigham and Women's Hospital, Boston, MA

Corresponding author: Ronny Drapkin, MD, PhD, Dana-Farber Cancer Institute, JF215D, 44 Binney St, Boston, MA 02115; e-mail: ronny_drapkin{at}dfci.harvard.edu

There are only a handful of concepts concerning cancer and carcinogenesis that are currently beyond dispute. One such dogma is the adenoma-carcinoma sequence and that a multistep accumulation of genetic alterations is required for transformation from a benign to a neoplastic tissue. The inevitable derivative of this dogma is that every invasive carcinoma is in fact a missed intraepithelial tumor, and furthermore, a late evolutionary stage in the sequence of development from a precursor lesion. Until fairly recently, high-grade serous ovarian carcinoma seemed to be one of the only known deviants of these concepts. In this article, we discuss the emergence of the fallopian tube fimbria as a field of origin for high-grade serous carcinomas and present a binary model of ovarian cancer pathogenesis that takes into consideration prior epidemiologic, morphologic, and genetic data. With the rise of the fallopian tube secretory epithelial cell as a cell of origin for high-grade pelvic serous carcinomas, the need to develop tools and model systems to characterize the biology and physiology of this cell is recognized.

published online ahead of print at www.jco.org on October 13, 2008

Supported by Grants No. P50 CA105009, K08 CA108748, R21 CA12468 from the National Cancer Institute, Ovarian Cancer Research Fund (individual investigator award and program project development award), Phi Beta Psi Sorority Charitable Trust, Fannie E. Ripple Foundation, Robert and Deborah First Fund, Randi and Joel Cutler Ovarian Cancer Research Fund, and the Columbia Hospital for Women Research Foundation.

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

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