Histological predictors of mismatch repair deficiency in endometrial endometrioid carcinoma

DNA mismatch repair (MMR) deficiency occurs in about 25-30% of endometrial endometrioid carcinoma cases. Universal MMR testing for all endometrial cancers has been adopted for its clinical relevance but remains uncommon, in developing countries, due to the associated cost. This study reevaluated histomorphology using often detected features to predict MMR deficiency in endometrial cancers. Eighty primary endometrial endometrioid carcinoma cases were included: forty with MLH1 and PMS2 loss shown by immunohistochemistry, and forty with proficient MMR proteins. Five histopathologic features were evaluated: intraluminal and extraluminal acute inflammation, intraluminal necrosis, surrounding diffuse lymphoid reaction, and micro-acinar architecture. The presence of at least three features was used as a cut-off to predict MMR deficiency. Thirty cases, both MMR-deficient and MMR-proficient, were blinded and distributed among four pathologists to assess interobserver agreement. The positive predictive value was 80.6%, the negative predictive value was 69.4%, the specificity was 85%, and the sensitivity was 62.5%. Interobserver agreement was moderate (kappa=0.537, p < 0.001). These pilot study results suggest that conventional histopathology can be a cost-effective screening tool for identifying endometrial endometrioid cancers likely to be MMR-deficient. Larger cohorts are needed to further validate the findings.