Association of endometrial cancer epigenetic mismatch repair deficiency with clinicopathologic factors and survival in a large, diverse community-based cohort

Abstract

Objectives

To evaluate associations between epigenetic mismatch repair deficiency (MMRd), clinicopathologic factors and overall survival in a diverse endometrial cancer cohort.

Methods

Retrospective analysis of patients with endometrioid cancer whose tumor mismatch repair status was classified by a universal screening program. Associations between epigenetic MMRd, race, other patient characteristics, tumor grade, and stage were assessed using multivariate regression. The Kaplan-Meier method and Cox regression were used to evaluate the association between epigenetic MMRd and overall survival, stratified by receipt of adjuvant therapy.

Results

Among 6477 patients, 14.3 % were found to have MMRd tumors due to epigenetic promoter hypermethylation. Compared to MMR proficient (MMRp) tumors, epigenetic MMRd was associated with age ≥ 70 (P < 0.001) and obesity (P = 0.03) but not smoking or comorbidity burden and were less common in Hispanic patients (P < 0.01) and individuals of lower socioeconomic status (P < 0.001). Epigenetic MMRd was associated with non-localized stage independent of tumor grade (aOR 1.28, 95 % CI 1.05–1.55, P = 0.01) and lower survival among the 4754 (73 %) patients not treated with any adjuvant therapy (HR 1.44, 95 % CI 1.09–2.01, P = 0.02) but not among 1723 (27 %) who received adjuvant chemotherapy, radiotherapy and/or immunotherapy (HR 0.89, 95 % CI 0.60–1.33, P = 0.56).

Conclusion

In a diverse community-based cohort, epigenetic MMRd characterized 14.3 % of endometrioid endometrial cancers and was associated with older age, obesity, and higher socioeconomic status. Controlling for these factors, epigenetic MMRd tumors were less common among Hispanic patients. Epigenetic MMRd was associated with non-localized stage independent of tumor grade and lower survival among patients who did not receive adjuvant therapy.