Mismatch Repair Status and Associated Clinicopathological Factors Among Young-Onset Colorectal Carcinoma

Background: Microsatellite instability (MSI) forms an important pathway in the pathogenesis of colorectal carcinoma (CRC). CRC with MSI is termed MMR-deficient (dMMR), and those with intact MMR genes are termed MMR-proficient (pMMR). The objective of the study is to determine the proportion of pMMR and dMMR among young-onset CRC patients and to evaluate the association of the clinicopathological profile with MMR status. Materials and Methods: This retrospective cross-sectional study was carried out in the Department of Pathology, RIMS Imphal, among patients diagnosed with CRC below 45 years of age from March 2021 to February 2023. The slides were re-evaluated regarding tumor types, grade, presence of lymphovascular invasion (LVI), and tumor-infiltrating lymphocytes (TILs). IHC staining was performed using antibodies MLH1, PMS2, MSH2, and MSH6. Loss of nuclear expression in all or any one of the antibodies was termed dMMR, whereas intact nuclear expression of all four antibodies was labeled pMMR. Results: A total of 44 cases were included in the study, of which 36 (81.82%) were pMMR and 8 (18.18%) were dMMR. The dMMR group had a mean age of 37.1 years, with a male preponderance (62.50%). The ascending colon was the most common site (50.00%), 62.50% presented as advanced disease (stage IV), 50.00% were moderately differentiated, 37.50% had mucinous morphology, and 62.50% showed the presence of TILs. Conclusion: A significant proportion of young-onset CRC in our study population demonstrated dMMR status. dMMR CRC had a higher histological grade, mostly presenting at an advanced stage.