Real-World Impact of Mismatch Repair Immunohistochemistry in Solid Tumors: A South Indian Cohort Study

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Abstract Deficient mismatch repair (dMMR) is a key biomarker for Lynch syndrome screening, adjuvant therapy decisions in early-stage colorectal and endometrial cancers, and immune checkpoint inhibitor (ICI) eligibility. However, real-world evidence on MMR immunohistochemistry (IHC) in resource-limited Indian settings remains limited. The objectives of the study were to determine the proportion of dMMR in solid tumors, to evaluate the patterns of MMR protein loss, to assess the clinical indications for MMR testing, and to analyze the impact of MMR status on treatment decisions. We retrospectively analyzed 191 patients who underwent MMR IHC using a four-antibody panel (MLH1, PMS2, MSH2, and MSH6) between January 2021 and March 2025 at a South Indian tertiary cancer center. Demographic, histopathologic, and clinical data were collected. Associations were analyzed using chi-square or Fisher's exact tests, and temporal trends in testing were assessed using the Cochran–Armitage's test. The study cohort comprised 191 patients (median age, 62 years; 50.8% male), with colorectal cancer being the predominant tumor type (68.5%), followed by upper gastrointestinal (15.7%) and endometrial cancers (6.3%). Adenocarcinoma accounted for 91.6% of tumors. Indications for testing included adjuvant therapy decisions (54.4%), ICI eligibility (45.5%), and Lynch syndrome screening (20.4%). dMMR was detected in 14.1% (n = 27), MMR-proficient in 85.3% (n = 163), and one case was inconclusive. Among dMMR tumors, colorectal cancer predominated (77.8%). The most common loss patterns were isolated PMS2 (18.5%) and MSH2 + MSH6 (18.5%), with nonclassical or complex loss in 37%. Among dMMR tumors, adjuvant therapy was omitted in 48.1%, modified in 22.2%, and ICI was offered in 29.6%. Testing uptake rose from 3 cases in 2021 to 51 in early 2025 (p < 0.01). Routine four-panel MMR IHC detected dMMR in 14% of solid tumors and significantly influenced management, underscoring its value as a cost-effective precision oncology tool in resource-constrained settings.

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