Mismatch repair status in high-grade endometrial carcinomas of endometrioid and non-endometrioid type

Purpose: To evaluate mismatch repair (MMR) status in a series of high-grade endometrial carcinomas and correlate it with several clinicopathological characteristics and with survival. Methods: One hundred and one patients with high-grade endometrial carcinoma, both of endometrioid and of non-endometrioid type were included in the study. The expression of MLH1, MSH2, MSH6 and PMS2 was evaluated by immunohistochemistry. Results: In our cohort, 41 women had an endometrioid and 60 women a non-endometrioid carcinoma. Endometrioid histotype was statistically more frequent in deficient MMR (dMMR) tumors (73.3%), while non-endometrioid carcinomas in proficient (pMMR) cases (73.8%) (p<0.001). When analyzing the group of endometrioid and non-endometrioid carcinomas separately, only dMMR endometrioid cancers were found to be statistically related to deep myometrial invasion, lymph-node metastases and advanced stage (p=0.035, p=0.011 and p=0.028, respectively). Univariate and multivariate analysis revealed no relation between MMR status and progression-free survival (PFS) or overall survival (OS). Adjuvant treatment was not found to influence the course of the disease. When MMR proteins were studied separately, MLH1/PMS2 loss was related to deep myometrial invasion (p=0.019 and p=0.036, respectively) and MSH6 loss to lymph-node metastases (p=0.04). Conclusions: In our group of high-grade endometrial carcinomas, MMR deficiency was statistically more frequent in endometrioid than in non-endometrioid cancers. Furthermore, only dMMR endometrioid type grade 3 carcinomas were found to be related with features indicative of aggressive behavior. Considering some unique relation of each MMR protein with distinct clinicopathological features, the assessment of all four proteins is proposed.