Early events in the pathogenesis of epithelial ovarian cancer

J Clin Oncol. 2008 Feb 20;26(6):995-1005. doi: 10.1200/JCO.2006.07.9970. Epub 2008 Jan 14.

Abstract

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.

Publication types

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

MeSH terms

  • Animals
  • Carcinoma / blood supply
  • Carcinoma / genetics*
  • Carcinoma / metabolism
  • Carcinoma / pathology*
  • Cell Transformation, Neoplastic
  • Disease Models, Animal
  • Female
  • Follicle Stimulating Hormone / metabolism
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation / metabolism
  • Luteinizing Hormone / metabolism
  • Microarray Analysis
  • Mutation*
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic
  • Ovarian Neoplasms / blood supply
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Signal Transduction

Substances

  • Luteinizing Hormone
  • Follicle Stimulating Hormone