Molecular Genetics of Endometrial Carcinoma

Annu Rev Pathol. 2019 Jan 24:14:339-367. doi: 10.1146/annurev-pathol-020117-043609. Epub 2018 Oct 17.


Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. Endometrioid endometrial carcinomas constitute approximately 85% of newly diagnosed cases; serous carcinomas represent approximately 3-10% of diagnoses; clear cell carcinoma accounts for <5% of diagnoses; and uterine carcinosarcomas are rare, biphasic tumors. Longstanding molecular observations implicate PTEN inactivation as a major driver of endometrioid carcinomas; TP53 inactivation as a major driver of most serous carcinomas, some high-grade endometrioid carcinomas, and many uterine carcinosarcomas; and inactivation of either gene as drivers of some clear cell carcinomas. In the past decade, targeted gene and exome sequencing have uncovered additional pathogenic aberrations in each histotype. Moreover, an integrated genomic analysis by The Cancer Genome Atlas (TCGA) resulted in the molecular classification of endometrioid and serous carcinomas into four distinct subgroups, POLE (ultramutated), microsatellite instability (hypermutated), copy number low (endometrioid), and copy number high (serous-like). In this review, we provide an overview of the major molecular features of the aforementioned histopathological subtypes and TCGA subgroups and discuss potential prognostic and therapeutic implications for endometrial carcinoma.

Keywords: carcinoma; carcinosarcoma; endometrioid; genomic; histopathology; molecular classification; serous.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Adenocarcinoma, Clear Cell / genetics
  • Carcinoma, Endometrioid / genetics
  • Cystadenocarcinoma, Serous / genetics
  • DNA Polymerase II / genetics
  • Endometrial Neoplasms / diagnosis
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Microsatellite Instability
  • Mutation*
  • PTEN Phosphohydrolase / genetics
  • Poly-ADP-Ribose Binding Proteins / genetics
  • Prognosis
  • Tumor Suppressor Protein p53 / genetics


  • Poly-ADP-Ribose Binding Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • DNA Polymerase II
  • POLE protein, human
  • PTEN Phosphohydrolase
  • PTEN protein, human