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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.

Racial disparities in incidence and survival exist for many human cancers. Racial disparities are undoubtedly multifactorial and due in part to differences in socioeconomic factors, access to care, and comorbidities. Within the U.S., fundamental causes of health inequalities, including socio-economic factors, insurance status, access to healthcare and screening and treatment biases, are issues that contribute to cancer disparities. Yet even these epidemiologic differences do not fully account for survival disparities, as for nearly every stage, grade and histologic subtype, survival among Black women is significantly lower than their White counterparts. To address this, we sought to investigate the proteomic profiling molecular features of endometrial cancer in order to detect modifiable and targetable elements of endometrial cancer in different racial groups, which could be essential for treatment planning. The majority of proteins identified to be significantly altered among the racial groups and that can be regulated by existing drugs or investigational agents are enzymes that regulate metabolism and protein synthesis. These drugs have the potential to improve the worse outcomes of endometrial cancer patients based on race.

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