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 <80 years for gastric (28.5% vs. 8.1%) and colorectal (13.5% vs. 5.9%) cancers, while endometrial cancers showed a non-significant increase with age (24.0% vs. 13.8%). Multivariable analysis identified primary site (adjusted odds ratio [aOR] = 4.20), age (aOR = 3.89), and female sex (aOR = 2.73) as independent predictors of dMMR in gastric cancer. For colorectal cancer, primary site (aOR = 16.88) and age (aOR = 1.91) were independently associated with dMMR.

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.