New insights on the pathogenesis of ovarian carcinoma: molecular basis and clinical implications

Gynecol Endocrinol. 2012 Aug;28(8):582-6. doi: 10.3109/09513590.2011.649595. Epub 2012 Feb 4.

Abstract

Ovarian carcinoma can be subdivided into two categories termed type I and type II. Type I tumours, usually having an indolent clinical behaviour, are often detected in early stage, and rarely harbour p53 gene mutations. Each histological type has a distinct molecular profile with mutations of genes involved in different signalling transduction pathways, such as KRAS, BRAF, CTNNB1, PTEN, PIK3CA and ARID1A. Type II tumours, accounting for 75% of the cases, have a very aggressive biological behaviour, are usually in advanced stage at presentation, harbour p53 gene mutations in 80% of the cases, and sometimes have alterations of homologous recombination (HR). Both type I and type II tumours arise from extra-ovarian precursors. Serous carcinomas derive from tubal epithelium, endometrioid and clear cell carcinomas from endometrial tissue, and mucinous and Brenner tumours from transitional epithelial cells located near the tubo-peritoneal junction. These new concepts on the pathogenesis of ovarian carcinoma could deeply modify both the preventive approach in women with germ-line BRCA₁ or BRCA₂ mutations and the treatment of patients with advanced or recurrent disease. For instance, BRAF inhibitors could be used in low-grade serous carcinomas, PIK3CA inhibitors could be employed in clear cell carcinoma, and poly (ADP-ribose) polymerase inhibitors could be used not only in hereditary ovarian carcinoma but also in non-hereditary, high-grade serous ovarian carcinoma which sometimes shows defective HR.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma / drug therapy*
  • Carcinoma / genetics
  • Carcinoma / metabolism
  • Carcinoma / secondary*
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology
  • Fallopian Tube Neoplasms / genetics
  • Fallopian Tube Neoplasms / metabolism
  • Fallopian Tube Neoplasms / pathology
  • Female
  • Humans
  • Hyperplasia
  • Molecular Targeted Therapy*
  • Mutation
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / secondary*
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins