Age- and sex-specific prevalence of deficient mismatch repair protein expression in gastric, colorectal, and endometrial cancers: a center-based study of older Japanese patients

Abstract Background Recent advancements in immunotherapy have revolutionized microsatellite instability-high (MSI-H) tumor management. Given the higher prevalence of MSI-H/deficient mismatch repair (dMMR) in older and female patients, characterizing these specific populations is clinically essential. We aimed to elucidate MSI-H/dMMR prevalence and predictive factors in older patients with gastric, colorectal, and endometrial cancers. Methods Using molecular and immunohistochemical analysis, we evaluated MSI status and MMR protein expression in 429, 647, and 54 patients with gastric, colorectal, and endometrial cancers, respectively (median age: 78 years for each group). Multivariable logistic regression analysis was performed to identify independent factors associated with dMMR status. Results MSI-H was identified in 17.0% and 9.8% of gastric and colorectal cancer cases, respectively, and dMMR was identified in 17.0%, 9.1%, and 18.5% of gastric, colorectal, and endometrial cancer cases, respectively. dMMR prevalence was significantly higher in patients aged ≥80 years than in those Conclusions Advanced age, sex, and primary tumor site are strong independent predictors of dMMR status. These findings underscore the value of routine MSI/MMR testing, particularly in older individuals, to optimize immunotherapy candidate selection.