New insights into the pathogenesis of serous ovarian cancer and its clinical impact.
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.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Keren
K
Levanon
Christopher
C
Crum
Ronny
R
Drapkin
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology*; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D018293:Cystadenoma, Serous / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D004847:Epithelial Cells / Q000473:pathology; D005187:Fallopian Tubes / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology* / Q000628:therapy