Mismatch repair protein expression in renal cell carcinoma: A comprehensive immunohistochemical study

Objectives: Microsatellite instability (MSI) is commonly associated with various malignancies, including colorectal, gastric, and endometrial carcinomas. The study aims to investigate the prevalence of mismatch repair (MMR) protein deficiency in the subtypes of renal cell carcinoma (RCC). Materials and Methods: Immunohistochemistry was done on 50 cases of RCC for four MMR proteins (MLH1, MSH2, MSH6, PMS2). The results were interpreted based on the percentage and intensity of expression, and the cases were categorized as MMR-proficient and MMR-deficient (dMMR). These were then correlated with clinicopathological parameters. Statistical analysis: One-way analysis of variance followed by least significant difference post hoc analysis; the Chi-square test was done to find the association between variables. The probability value ( p < 0.05) was considered statistically significant. Results: There were 50 cases of RCC. The male-to-female ratio was 3.5:1. Clear cell RCC was the most common subtype. 28% ( n = 14) of the study cases were dMMR. The most frequent expression pattern among dMMR cases was combined loss of MSH2 and MSH6 (12%), followed by a complete loss of all 4 markers (10%). There was a significant correlation of the expression pattern of MMR proteins with the tumor grade, renal vein/sinus involvement, and perinephric fat invasion. Conclusions: MMR deficiency was observed in 28% of RCC cases. The association between MMR status and tumor grade, renal vein/sinus involvement, highlights the clinical relevance of MMR analysis in RCC. These findings contribute to our understanding of the molecular underpinnings of RCC and may inform future diagnostic and therapeutic strategies.