Endometrial Cancer Characteristics and Risk of Recurrence

Abstract

Objectives: To describe clinicopathologic characteristics and survival outcomes of endometrial adenocarcinomas stratified by mismatch repair (MMR) status.

Methods: Single-institution, retrospective study of all women with endometrioid adenocarcinomas treated from January 2012 through December 2017. Patients were categorized into one of three groups based on MMR testing: intact MMR expression (MMR+), probable MMR mutation (MMR-), or MLH1 hypermethylation (hMLH1+). Demographics, pathologic characteristics, recurrence rates, and survival differences were analyzed.

Results: In total, 316 women were included in the analysis: 235 (74.4%) patients in the MMR+ group, 10 (3.1%) in the MMR- group, and 71 (22.5%) in the hMLH1+ group. Patients with hMLH1+ were significantly older, exhibited higher-grade histology and presence of lymphovascular space invasion, and were more likely to have received adjuvant treatment. The early stage hMLH1+ patients were more likely to recur (15.3% hMLH1+ vs 2.3% MMR+ vs 12.5% MMR-, P < .001). Hypermethylation remained a significant predictor of recurrence in multivariable analysis (odds ratio, 5.09; 95% confidence interval [CI], 1.54-16.86; P = .008). Recurrence-free survival was significantly reduced in early stage hMLH1+ (hazard ratio, 7.40; 95% CI, 2.80-21.62; P < .001).

Conclusions: Women with hMLH1+ endometrial cancer have worse prognostic features and recur more frequently, even in patients traditionally considered low risk for recurrence.

Keywords: DNA mismatch repair; Endometrial neoplasms; Epigenomics; Lynch syndrome; Microsatellite repeats.