Recent studies have suggested an increased risk of
prostate cancer in men with
Lynch syndrome driven by germline mutations in mismatch repair (MMR) genes. However, the incidence and clinical implication of
MMR deficiency in sporadic
prostate cancers remain poorly understood. We immunohistochemically stained for MLH1, MSH2, MSH6, and PMS2 in a set of tissue microarray consisting of 220 radical
prostatectomy specimens and evaluated the relationship between loss of their expression and available clinicopathological features. MLH1, MSH2, MSH6, and PMS2 were lost in 2 (0.9%), 6 (2.7%), 37 (16.8%), and 27 (12.3%)
prostate cancers, respectively. Loss of at least 1 MMR
protein was identified in 50 (22.7%) cases. There were no statistically significant associations between
MMR deficiency and patient age, family history of
prostate cancer, Gleason score, or pT/pN stage. Nonetheless, the levels of preoperative
prostate-specific antigen (PSA) were significantly (P = .015) higher in patients with
MMR deficiency (mean ± SD: 9.12 ± 9.01 ng/mL) than in those without abnormal MMR (5.76 ± 3.17 ng/mL). There were 15 (6.8%) cases showing loss of at least 2 MMR
proteins, which was not significantly associated with PSA level or
tumor grade/stage. Additionally, 5 and 2 cases showed losses of at least 3 MMR
proteins and all 4
proteins, respectively. Kaplan-Meier analysis revealed no significant associations between loss of MLH1 (P = .373), MSH2 (P = .348), MSH6 (P = .946), or PMS2 (P = .681), or at least 1 (P = .477), 2 (P = .486), or 3 (P = .352) MMR
proteins and biochemical recurrence. Further analyses of the data on
programmed death-ligand 1 (PD-L1) expression previously stained in the same set of tissue microarray demonstrated associations between loss of ≥2 MMR
proteins and a higher rate of PD-L1 expression in
cancer cells (17.2% vs 5.2%; P = .033) as well as between cases showing both loss of ≥1 MMR
protein(s) and PD-L1 expression in
tumor-infiltrating immune cells vs a higher risk of biochemical recurrence (P = .045). MMR
protein loss was seen in a subset of
prostate cancers. Interestingly, it was associated with significantly higher levels of PSA. Moreover, immunohistochemical detection of MMR
proteins together with other
proteins, such as PD-L1, might be helpful in predicting
tumor recurrence following radical
prostatectomy.