Clinicopathologic analysis of MMR gene mutations and uterine adenocarcinomas: An updated population-based study.

Abstract

e18100 Background: Endometrial carcinoma frequently harbors genetic alterations in genes encoding mismatch repair (MMR) enzymes, a finding which has important implications for adjuvant therapy. The aim of this study is to determine an optimal screening strategy to detect MMR mutations for each histologic subtype of endometrial carcinoma (EC). Methods: We performed a comparative analysis of the demographic, clinical, pathologic, and molecular data, including MLH1, MLH3, PMS1, PMS2, MSH2, MSH3, MSH6, and EPCAM, for 562 patients from The Cancer Genome Atlas database (TCGA), stratified by tumor histologic subtype. Results: Molecular data was available for 562 patients, of which 162 (28.8%) had tumors that were positive for MMR mutations. We did not separate somatic and germline mutation. Of these tumors, the penetrate rate of FIGO grade 3 endometrioid endometrial carcinoma (EEC G3) (84/184, 45.7%) was significantly higher than the one of uterine serous carcinoma (USC) (35/156, 22.4%) ( p < 0.001), grade 2 (EEC G2) (26/129, 20.2%) ( p < 0.001), and grade 1 (EEC G1) (17/93, 18.3%) ( p < 0.001). Of EEC G3 tumors, patients with MMR gene mutations were significantly older ( p = 0.024) or had lower BMI's than MMR mutation noncarriers ( p = 0.028). Of 562 endometrial carcinomas, alterations in MSH2 (n = 55), MSH6 (n = 54), MSH3 (n = 50) were the most frequent mutations. There were no differences in overall survival and progression-free interval between MMR mutation carriers and nonmutation carriers (p > 0.05) except that PFI with MMR gene mutation was higher than with MMR proficiency in EEC G3 ( p = 0.014). Conclusions: EEC G3 harbored the most MMR mutations among EC. EEC G3 and USC could be more considered to screen MMR mutation due to more MMR mutations occurred in EEC G3 and USC than did among EEC G2 and EEC G1. Besides MLH1, MSH2, MSH6, PMS2 and EPCAM mutation , MLH3, MSH3, PMS1 mutation could be screened in patients with newly diagnosed endometrial carcinoma. [Table: see text]