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
Tomio Arai, Akiko Komatsu, Takuya Nagasaka, Seiya Kamino, Hirofumi Rokutan, Keisuke Nonaka, Nobuo Kanazawa, Tetsuya Nakazato, Toshiyuki IshiwataAbstract
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.