Immunophenotypic Evaluation of Mismatch Repair Proteins in Various Solid Tumours: A Cross-sectional Study from a Tertiary Care Cancer Centre in Rajasthan, India

Introduction: Mismatch Repair (MMR) proteins are essential in correcting DeoxyRibo Nucleic Acid (DNA) replication errors, including point mutations, to maintain genetic stability. Among atleast seven MMR proteins in humans, four- MLH1 (MutL homolog 1), MSH2 (MutS homolog 2), MSH6 (MutS homolog 6), and PMS2 (Postmeiotic segregation increased 2) are most significant in cancer biology, particularly in Colorectal Carcinoma (CRC), gastric, endometrial, and ovarian cancers. Deficiencies in these genes can lead to Microsatellite Instability (MSI), which promotes tumourigenesis. Aim: The present study done to assess the expression of MMR proteins and their association with clinicopathological features in solid tumours like colon, liver, stomach, gall bladder and others. Materials and Methods: The present retrospective and comparative study was conducted at a North Indian Cancer Centre at Jaipur, Rajasthan, India for three years, 55 cases of various solid tumours were examined for the expression of MMR proteins using immunohistochemistry. The cases were categorised into two groups: proficient (normal expression of MMR proteins, low MSI probability) and deficient (loss of MMR proteins, high MSI probability). The immunophenotypic expression was analysed in relation to clinical and pathological parameters by tabulating the data in Microsoft Excel sheet and statistical analysis was done by using the Statistical Package for Social Sciences (SPSS) statistics software windows version 22.0 released 2013. Results: Results showed that 8 (14.5%) out of 55 patients had a loss of MMR protein expression. Of these cases, 5 (62.5%) displayed a combined loss of MLH1 and PMS2, while 3 (37.5%) showed a combined loss of MSH2 and MSH6. All cases with MMR deficiency were located proximal to the splenic flexure and exhibited mucinous differentiation along with high levels of Tumour-infiltrating Lymphocytes (TILs). The mean age in the proficient group (59.4 years) was higher compared to the deficient group (54.5 years), with males {5 (62.5%) in MMRd and 25 (53.2%) MMRp} being more commonly affected than females {3 (37.5%) in MMRd and 22 (46.5%) in MMRp} in both groups. Adenocarcinoma was the predominant histological type in both groups {5 (62.5%) in MMRd and 30 (63.8%) in MMRp}. Conclusion: The study highlights the importance of MMR protein testing, particularly for CRC patients aged around 50 years with low-grade tumours. However, given the limited sample size, larger studies are needed to further explore the relationship between MMR protein deficiencies and clinicopathological features in various cancers.