Defective DNA mismatch repair influences expression of endometrial carcinoma biomarkers

Ekene I. Okoye, Amanda S. Bruegl, Bryan Fellman, Rajyalakshmi Luthra, Russell R. Broaddus

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Endometrial endometrioid carcinomas are related to estrogen excess and express estrogen and progesterone receptors. However, hormone receptor expression can be variable from tumor to tumor, and this variability is not always explained by differences in tumor grade. Variable expression of other biomarkers that may be used in the diagnostic work-up of endometrial cancer has also been noted. We hypothesized that mismatch repair (MMR) defects may contribute to this variability. A total of 411 unselected endometrial carcinomas were evaluated for immunohistochemical expression of DNA MMR proteins and MLH1 methylation. Loss of immunohistochemical expression of MLH1, MSH2, MSH6, or PMS2 was defined as MMR deficient; positive expression was defined as MMR intact. A case-control cohort of 80 Grade 2 endometrioid carcinomas was selected from this set (40 MMR deficient, 40 MMR intact). Cases were matched for histotype, grade, and age. Estrogen receptor, progesterone receptor, CK7, CK20, and Pax-8 immunohistochemistry was evaluated. The median percentage of CK7 + tumor cells was significantly lower in the MMR deficient group compared with the MMR intact group. The mean percentage of tumor cells exhibiting estrogen receptor expression was similar in both the MMR-deficient and MMR intact groups. However, there was greater variability in the MMR-deficient group. Our study shows that MMR defects influence the expression of clinically important biomarkers for endometrioid-type endometrial carcinoma as decreased cytokeratin 7 expression is more commonly associated with MMR deficiency.

Original languageEnglish (US)
Pages (from-to)8-15
Number of pages8
JournalInternational Journal of Gynecological Pathology
Volume35
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • Cytokeratin 7
  • Endometrial carcinoma
  • Endometrioid carcinoma
  • Estrogen receptor
  • Microsatellite instability
  • Mismatch repair genes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Obstetrics and Gynecology

Fingerprint Dive into the research topics of 'Defective DNA mismatch repair influences expression of endometrial carcinoma biomarkers'. Together they form a unique fingerprint.

  • Cite this