Immunohistochemical and genetic profiles of endometrioid endometrial carcinoma arising from atrophic endometrium

Gynecol Oncol. 2015 May;137(2):245-51. doi: 10.1016/j.ygyno.2015.03.007. Epub 2015 Mar 12.

Abstract

Objective: Endometrial carcinomas are divided into type I endometrioid endometrial carcinomas (EECs), thought to arise from hyperplastic endometrium, and type II nonendometrioid endometrial carcinomas, thought to arise from atrophic endometrium. However, a minority (20%) of EECs have atrophic background endometrium, which was shown to be a marker of a worse prognosis. This study compares the immunohistochemical and genetic profiles of this possible third type to that of the known two types.

Methods: 43 patients with grade 1 EEC and hyperplastic background endometrium (type I), 43 patients with grade 1 EEC and atrophic background endometrium (type III) and 21 patients with serous carcinoma (type II) were included (n=107). Tissue microarrays of tumor samples were immunohistochemically stained for PTEN, L1CAM, ER, PR, p53, MLH1, PMS2, β-catenin, E-cadherin and MIB1. The BRAF, KRAS, and PIK3CA genes were analyzed for mutations.

Results: A significantly higher expression of ER and PR, and a lower expression of L1CAM, p53 and MLH1 were found in type I and III compared to type II carcinomas. Expression of E-cadherin was significantly reduced in type III compared to type I carcinomas. Mutation analysis showed significantly less mutations of KRAS in type III compared to type I and II carcinomas (p<0.01).

Conclusion: There appear to be slight immunohistochemical and genetic differences between EECs with hyperplastic and atrophic background endometrium. Carcinogenesis of EEC in atrophic endometrium seems to be characterized by loss of E-cadherin and a lack of KRAS mutations. As expected, endometrioid and serous carcinomas were immunohistochemically different.

Keywords: Background endometrium; Endometrial carcinoma; Endometrioid; Genetical; Immunohistochemistry.

MeSH terms

  • Atrophy
  • Carcinoma, Endometrioid / genetics*
  • Carcinoma, Endometrioid / metabolism*
  • Carcinoma, Endometrioid / pathology
  • Carcinoma, Endometrioid / surgery
  • Cohort Studies
  • DNA Mutational Analysis
  • Endometrial Hyperplasia / pathology
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / pathology
  • Endometrial Neoplasms / surgery
  • Endometrium / pathology*
  • Female
  • Humans
  • Immunohistochemistry