Immunohistochemical Expression of Mismatch Repair Proteins in Colorectal Carcinomas with Histopathological Correlation in a Quaternary Care Centre in South India

Background and Aims: Colorectal carcinomas are one of the most prevalent malignant neoplasms globally and are characterised by a range of genetic and epigenetic alterations, primarily chromosomal instability and microsatellite instability. This study aims to assess the expression of MMR proteins in patients with colorectal carcinoma and to examine the relationship between MMR status and various histopathological and clinical variables. Material and Methods: All biopsy and resection cases of colorectal carcinoma on which MMR was done by IHC were studied from December 2022 to November 2023. Histopathological and immunohistochemical assessments of mismatch repair proteins were done for 153 colorectal carcinoma patients in formalin-fixed paraffin-embedded tumour tissues. Statistical analysis was carried out using SPSS software (IBM, 28.0). Results: Out of 153 cases collected, 23 cases (15%) had a loss of MMR expression, and 130 cases (85%) had no loss of MMR protein. Combined loss of MLH1 and PMS2 was found in 16 cases (70%), combined loss of MSH2 and MSH6 was found in five cases (21%) and isolated loss of PMS2 was found in two cases (9%). Adenocarcinoma NOS, mucinous differentiation, medullary pattern, right-sided tumours, female gender and younger age group correlated with loss of MMR expression. Conclusion: Molecular study is the first approach for detecting MSI associated with CRC, IHC is a very good alternative to identify microsatellite instability. IHC methods can be used as a reliable tool in the workup for MSI as IHC markers (antibodies to the MMR proteins) are now easily accessible in most laboratories.