MSX1-A Potential Marker for Uterus-Preserving Therapy of Endometrial Carcinomas

Int J Mol Sci. 2020 Jun 25;21(12):4529. doi: 10.3390/ijms21124529.

Abstract

Prognostic factors are of great interest in patients with endometrial cancer. One potential factor could be the protein MSX1, a transcription repressor, that has an inhibitory effect on the cell cycle. For this study, endometrioid endometrial carcinomas (n = 53), clear cell endometrial carcinomas (n = 6), endometrioid ovarian carcinomas (n = 19), and clear cell ovarian carcinomas (n = 11) were immunochemically stained for the protein MSX1 and evaluated using the immunoreactive score (IRS). A significant stronger expression of MSX1 was found in endometrioid endometrial carcinomas (p < 0.001), in grading 2 (moderate differentiation) (p = 0.001), and in tumor material of patients with no involvement of lymph nodes (p = 0.031). Correlations were found between MSX1 expression and the expression of β-Catenin, p21, p53, and the steroid receptors ERα, ERβ, PRα, and PRβ. A significant (p = 0.023) better survival for patients with an MSX1 expression in more than 10% of the tumor cells was observed for endometrioid endometrial carcinomas (21.3 years median survival (MSX1-positive) versus 17.3 years (MSX1-negative)). Although there is evidence that MSX1 expression correlates with improved long-term survival, further studies are necessary to evaluate if MSX1 can be used as a prognostic marker.

Keywords: DNA-methylation; MSX1; cell-cycle; endometrial carcinoma; uterus-preserving therapy.

MeSH terms

  • Adenocarcinoma, Clear Cell / metabolism
  • Adenocarcinoma, Clear Cell / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Endometrioid / metabolism
  • Carcinoma, Endometrioid / pathology
  • DNA Methylation / genetics
  • Endometrial Neoplasms / genetics
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • MSX1 Transcription Factor / genetics
  • MSX1 Transcription Factor / metabolism*
  • MSX1 Transcription Factor / physiology
  • Middle Aged
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Transcription Factors / metabolism
  • Tumor Suppressor Protein p53 / metabolism
  • Uterine Neoplasms / pathology
  • Uterus / metabolism
  • Uterus / pathology

Substances

  • Biomarkers, Tumor
  • MSX1 Transcription Factor
  • MSX1 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53