Molecular pathology of endometrial hyperplasia and carcinoma

Hum Pathol. 2001 Jun;32(6):569-77. doi: 10.1053/hupa.2001.25929.


Four different genetic abnormalities may occur in endometrioid adenocarcinomas of the endometrium (mircosatellite instability and mutations in the PTEN, k-RAS and beta-catenin genes), whereas nonendometrioid carcinomas of the endometrium often have p53 mutations and loss of heterozygosity on several chromosomes. Occasionally, a nonendometrioid carcinoma may develop as a result of dedifferentiation of a preexisting endometrioid carcinoma; in such a case, the tumor exhibits overlapping clinical, morphologic, immunohistochemical, and molecular features of the 2 types. The insaturation of microsatellite instability in endometrial carcinogenesis seems to occur late in the transition from complex hyperplasia to carcinoma, and it is preceded by progressive inactivation of MLH-1 by promoter hypermethylation. Moreover, the endometrioid adenocarcinomas that exhibit microsatellite instability show a stepwise progressive accumulation of secondary mutations in oncogenes and tumor suppressor genes that contain short-tandem repeats in their coding sequences. Mutations in the PTEN and k-RAS genes are also frequent in endometrioid adenocarcinomas of the endometrium, particularly in the tumors that exhibit microsatellite instability, whereas beta-catenin mutations do not seem to be associated with such a phenomenon.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cytoskeletal Proteins / genetics
  • DNA Methylation
  • Endometrial Hyperplasia / genetics*
  • Endometrial Neoplasms / genetics*
  • Female
  • Genes, p53 / genetics
  • Genes, ras / genetics
  • Humans
  • Microsatellite Repeats / genetics
  • Mutation
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / genetics
  • Trans-Activators*
  • Tumor Suppressor Proteins*
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Trans-Activators
  • Tumor Suppressor Proteins
  • beta Catenin
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human