The Role of KRAS in Endometrial Cancer: A Mini-Review

Anticancer Res. 2019 Feb;39(2):533-539. doi: 10.21873/anticanres.13145.

Abstract

Endometrial cancer (EC) is the most common cancer of the female genital tract, resulting annually in 76,000 related deaths worldwide. EC originates either from oestrogen-related proliferative endometrium (type I, endometrioid), or from atrophic endometrium (type II, non-endometrioid). Each type of EC is characterized by different molecular profile alterations. The Kirsten rat sarcoma viral oncogene homolog (KRAS) gene encodes a signalling protein which moderates response to various extracellular signals via down-regulation of the mitogen-activated protein kinase (MAPK) or phosphoinositide-3-kinase/v-akt murine thymoma viral oncogene (PI3K/AKT) pathways. This article reviews the role of KRAS in predicting transition from hyperplastic endometrium to early-stage well-differentiated EC, as well as further invasive proliferation of the tumour to advanced-stage disease. KRAS seems to be directly associated with type I EC, and most studies support its early involvement in carcinogenesis. Current evidence correlates KRAS mutations with increased cell proliferation and apoptosis, as well as up-regulation of endometrial cell oestrogen receptors. Tumours positive for KRAS mutation can harbour hypermethylation-related changes in genome expression, and this can be the cause of concurrent loss of DNA repair proteins. Despite some evidence that KRAS mutation status affects cancer progression, a consensus is yet to be reached. Based on the available evidence, we suggest that screening for KRAS mutations in patients with hyperplastic endometrium or early-stage type I EC, may provide important information for prognosis stratification, and further provision of personalised treatment options.

Keywords: Endometrial cancer; KRAS; endometrial hyperplasia; molecular biomarkers; review.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Cell Proliferation
  • Disease Progression
  • Endometrial Neoplasms / metabolism*
  • Endometrium / metabolism
  • Estrogens / metabolism
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic*
  • Genes, ras
  • Humans
  • Mutation
  • Neoplasm Staging
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • Receptors, Estrogen / metabolism

Substances

  • Biomarkers, Tumor
  • Estrogens
  • KRAS protein, human
  • Receptors, Estrogen
  • Proto-Oncogene Proteins p21(ras)