New insights into the pathogenesis of serous ovarian cancer and its clinical impact

J Clin Oncol. 2008 Nov 10;26(32):5284-93. doi: 10.1200/JCO.2008.18.1107. Epub 2008 Oct 14.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / pathology*
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / pathology*
  • Cystadenocarcinoma, Serous / therapy
  • Cystadenoma, Serous / genetics
  • Cystadenoma, Serous / pathology*
  • Cystadenoma, Serous / therapy
  • Epithelial Cells / pathology
  • Fallopian Tubes / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology*
  • Ovarian Neoplasms / therapy
  • Precancerous Conditions / genetics
  • Precancerous Conditions / pathology*
  • Precancerous Conditions / therapy