Assessment of Mismatch Repair Gene Expression in Colorectal Carcinoma: A Two-Year Single-Center Study

Abstract

Background:Mismatch repair MMR deficiency is a crucial biomarker in colorectal carcinoma (CRC) with the diagnosis, prognosis, and treatment significance of the MMR deficiency. MMR deficiency testing has become universally recommended to allow for Lynch syndrome screening and for the identification of the candidates for immune checkpoint inhibitor therapy. This study aims to evaluate the incidence of MMR protein expression in Iraqi patients with colorectal carcinoma and study their association with clinicopathological parameters. Methods: The retrospective cross-sectional study consisted of 34 patients histopathologically confirmed with primary colorectal carcinoma and these patients underwent surgical resection between January 2024 to December 2025 in Al-Warith International Cancer Institute, Karbala, Iraq. The immunohistochemistry expression for MLH1, PMS2, MSH2, and MSH6 genes were assessed using formalin-fixed, paraffin-embedded tissue sections. The correlation between the MMR and clinicopathological factors was analyzed using Fisher’s exact test or Fisher-Freeman-Halton exact test, as appropriate. Results: dMMR protein expression was identified in 4 out of 34 patients (11.8%), whereas 30 out of 34 patients (88.2%) showed proficient MMR expression. The most frequent MMR protein deficiency pattern was the MLH1/PMS2 deficiency, while the second most frequent was the MSH2/MSH6 deficiency, and only 1 out of 34 patients had MSH6 deficiency alone. There was a statistically significant correlation between dMMR expression and the location of the tumor (P = 0.009) and tumor grade (P = 0.035). No correlation was found between MMR protein expression and age, sex, cancer staging, histological type or lymph node involvement. No statistically significant correlation was observed with age, sex, tumor staging, histological type, or lymph node involvement. Conclusion: The incidence of dMMR in the studied Iraqi population was comparable to that proposed in earlier regional and international studies. Despite the existence of a relationship between the site of the tumor and its grade, it is necessary to mention that these findings should be taken into account with reservation due to the small number of participants and need for further validation.