Incidence of Mismatch Repair Protein Deficiency and Associated Clinicopathologic Features in a Cohort of 104 Ovarian Endometrioid Carcinomas

Am J Surg Pathol. 2019 Feb;43(2):235-243. doi: 10.1097/PAS.0000000000001165.

Abstract

Patients with Lynch syndrome have up to a 24% risk of developing ovarian carcinoma, but universal mismatch repair (MMR) protein testing of ovarian carcinomas is not standard practice in most institutions. We reviewed 104 unselected ovarian endometrioid carcinomas (OEC) for various clinicopathologic features to determine if any are predictive of MMR loss. Immunohistochemistry for all 4 MMR proteins was performed followed by MLH1 promoter methylation analysis when indicated. Overall, patients had a mean age of 55 years and tumors averaged 12 cm. Most (72%) patients had stage I tumors, 63% were grade 1, and 30% had a synchronous stage IA endometrial endometrioid carcinoma. Peritumoral lymphocytes and intratumoral stromal inflammation were rare, but tumor-infiltrating lymphocytes averaged 47/10 high-power fields. Endometriosis was noted in 71%, adenofibromatous background in 14%, and both in 14% of tumors. Metaplastic changes were common and included squamous metaplasia (63%), clear cell change (32%), mucinous differentiation (24%), and sex cord-like elements (13%). When follow-up was available (n=99), 78% of patients were alive and well, 12% died from disease, 6% died from other causes, and 4% were alive with disease. Unmethylated, MMR-deficient OECs were identified in 7% of the cohort and included MSH2/MSH6 (n=4), MSH6 (n=2), and PMS2 (n=1). All these tumors were stage I, 71% grade 1, and 57% had a synchronous endometrial endometrioid carcinoma. Among patients in this group with follow-up (n=5), all were alive without evidence of disease (mean 150 mo). Given that no clinicopathologic features were associated with MMR deficiency on univariate analysis, this study highlights the importance of universal MMR screening in OECs.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Endometrioid / pathology*
  • DNA Mismatch Repair*
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / biosynthesis
  • Female
  • Humans
  • Incidence
  • Middle Aged
  • Mismatch Repair Endonuclease PMS2 / analysis
  • Mismatch Repair Endonuclease PMS2 / biosynthesis
  • MutL Protein Homolog 1 / analysis
  • MutL Protein Homolog 1 / biosynthesis
  • MutS Homolog 2 Protein / analysis
  • MutS Homolog 2 Protein / biosynthesis
  • Ovarian Neoplasms / pathology

Substances

  • DNA-Binding Proteins
  • G-T mismatch-binding protein
  • MLH1 protein, human
  • PMS2 protein, human
  • MSH2 protein, human
  • Mismatch Repair Endonuclease PMS2
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein