The Frequency and Clinical Implication of Mismatch Repair Protein Deficiency in Chinese Patients with Ovarian Clear Cell Carcinoma

Abstract Background: To assess the prevalence of deficient mismatch repair (MMR) in Chinese ovarian clear cell carcinoma (CCC) patients and its association with clinicopathologic features.Methods: Immunohistochemistry with four antibodies against MLH1, PMS2, MSH2 and MSH6 were performed on whole section slides. Results were correlated with clinicopathologic variables.Results: A total of 108 cases were included in the study, with a median age of 52 years at first diagnosis. Early-stage disease and platinum-sensitive recurrence accounted for 62.3% and 69.6%, respectively. Overall, the estimated 5-year overall survival was 70.3% and 20.7% in patients with early and late stage tumor, respectively. Deficient MMR were identified in 5.6% (6/108) of the cohort and included MSH2/MSH6 (n=4) and MLH1/PMS2 (n=2). The average age of the six patients was 45.6 years. The rate of MMR-deficient tumors in women ≤ 50 years was relatively higher than that those over 50 years (10.0% Vs. 2.9%; P=0.266). A half of the patients with deficient MMR were diagnosed with a synchronous (endometrial or colorectal) and metachronous (endometrial) cancer, significantly more than those intact counterparts (P=0.002). All the six patients had early-stage tumor and the majority (83.3%) were platinum-sensitive. The median progression-free survival was slightly higher in patients with defective MMR expression than those intact counterparts (30 months Vs. 27 months), although significance was not achieved (P=0.471). Conclusions: Ovarian CCC patients with young age and concurrent diagnosis of endometrial and colorectal cancer are more likely to have MMR-deficient tumors. It merits further evaluation whether patients harboring MMR abnormality has favorable prognosis.