A comparative analysis between clinicopathologic correlates of mismatch repair status compared to combined mismatch repair status and microsatellite instability in Filipino patients with colorectal cancer.

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Background: Colorectal cancer (CRC) management relies on molecular classification, specifically the Mismatch Repair (MMR) status and its corresponding phenotype, Microsatellite Instability (MSI). This molecular status is critical for determining eligibility for adjuvant chemotherapy in Stage II disease and, crucially, for immunotherapy. Given the high concordance between MMR protein expression (assessed by Immunohistochemistry, IHC) and MSI status (assessed by PCR), this study investigates whether MMR testing alone can reliably indicate MSI status and seeks to identify associated clinicopathologic characteristics, offering a potentially more cost-effective diagnostic strategy in a resource-constrained setting. Methods: This was a cross-sectional analytical study utilizing retrospective data from 136 adult patients with definitive CRC diagnosis at St. Luke’s Medical Center Quezon City from January 2021 to October 2025. Data on MMR status (IHC) was available for all patients, and a subset of 49 patients also had paired MSI status (PCR) results. Univariate and multivariable logistic regression analyses were used to determine the association of clinicopathologic factors (age, sex, tumor location, clinical stage, and histologic variant) with Deficient MMR (dMMR) status. The level of agreement between MMR and MSI was assessed using Cohen's Kappa statistic. Results: A high overall concordance rate of 87.76% was observed between MMR (IHC) and MSI (PCR) status in the paired subset. Analysis of the entire cohort revealed a 14.71% prevalence of dMMR. Multivariable logistic regression identified right-sided tumor location [Adjusted OR (AOR): 5.51; 95% CI: 1.07–28.49] and aggressive histologic variants (Mucinous/Signet Ring) [AOR: 18.7; 95% CI: 3.35–104.19] as significant independent predictors of dMMR status. While right-sided tumor location remained a significant predictor in the combined dMMR/MSI-H analysis, the association with histologic variants lost statistical significance in this smaller subset. Conclusions: MMR immunohistochemistry demonstrated high concordance with MSI testing, supporting its use as a reliable and cost-effective screening tool for molecular stratification in CRC. This study definitively establishes a high-risk phenotype in Filipino patients: right-sided tumors and aggressive histologic variants are strong independent predictors of Deficient MMR status. These findings provide essential local evidence to guide precision oncology, suggesting that accessible MMR IHC testing can be confidently integrated into routine practice to identify patients eligible for targeted therapies like immunotherapy, thereby optimizing resource allocation and improving clinical outcomes.