SCREENING OF COLORECTAL CARCINOMA BY MISMATCH REPAIR DEFECT THROUGH IMMUNOHISTOCHEMISTRY A SINGLE CENTER STUDY
DOI:
https://doi.org/10.71000/nk5tja02Keywords:
Immunohistochemistry, Microsatellite instability, Mismatch repair, Tumor-infiltrating lymphocytes, Adenocarcinoma, Colorectal Neoplasms, Neoplasm GradingAbstract
Background: Colorectal carcinoma (CRC) is the third most commonly diagnosed malignancy worldwide and develops through complex genetic and epigenetic mechanisms, including chromosomal instability, microsatellite instability, and CpG island methylator pathways. Defects in mismatch repair (MMR) genes lead to microsatellite instability, which is central to Lynch syndrome and influences prognosis and therapeutic response. While molecular assays remain the gold standard for MSI detection, immunohistochemistry (IHC) offers a practical, cost-effective, and accessible alternative, particularly in resource-limited settings. This study aimed to evaluate the utility of MMR IHC in screening for deficient MMR status in relation to clinico-pathological features in a local population.
Objective: To assess the role of immunohistochemistry in detecting MMR-deficient colorectal carcinoma and to correlate MMR status with clinico-pathological characteristics.
Methods: A descriptive cross-sectional study was conducted at the Chughtai Institute of Pathology from March 2023 to February 2024. Seventy-four colorectal carcinoma resection specimens were analyzed. Immunohistochemistry for MLH1, PMS2, MSH2, and MSH6 was performed using an automated staining platform. Demographic and pathological parameters—including age, gender, tumor site, morphology, grade, and tumor-infiltrating lymphocytes (TILs)—were recorded and correlated with MMR expression status.
Results: Loss of MMR protein expression was identified in 32 of 74 cases (43.2%). Combined loss of MLH1 and PMS2 accounted for 18 cases (24.3%), dual loss of MSH2 and MSH6 in 3 cases (4.1%), isolated loss of MSH2 in 3 cases (4.1%), isolated loss of PMS2 in 2 cases (2.7%), and complete loss of all four proteins in 6 cases (8.1%). Retained MMR expression was observed in 42 cases (56.8%). A statistically significant association was found between MMR deficiency and TILs (p=0.02), whereas no significant relationship was observed for age, gender, tumor site, morphology, or tumor grade.
Conclusion: Although molecular techniques remain the definitive approach for MSI detection, MMR IHC represents a reliable, economical, and accessible screening tool. The findings support universal IHC-based MMR screening for all newly diagnosed colorectal carcinomas, irrespective of clinico-pathological parameters.
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Copyright (c) 2025 Maryam Akhtar, Asma Zafar, Saira Rathore, Anila Chughtai, Zubaria Rafique, Akhtar Sohail Chughtai (Author)
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