Immunohistochemical analysis of Mismatch repair-deficient gene expression in unselected Colorectal Cancer: An update of tertiary cancer center from North India

Abstract

Colorectal cancer (CRC) is the third most deadly and fourth most commonly diagnosed cancer in the world. The present study has been carried out to see the frequency of lost MMR protein expression and its histopathological characteristics in unselected colorectal cancer patients from north India. 103 consecutive patients of colorectal cancer who underwent surgery between 2014-2018 in a tertiary care teaching hospital in North India were included in the study. The study was approved by the Institute’s Ethical Committee. MMR protein status was determined by Immunohistochemistry (IHC) to examine the expression of MLH1, PMS2, MSH2 and MSH6 on paraffin-embedded tissues. Patients with MLH1deficient protein were further followed by BRAF V600E testing. The histopathological features were correlated with MMR protein expression. IHC results revealed a loss of different MMR protein expression in 33 (32%) patients. the most frequent loss was lost MSH2 12(36.4%) followed by MLH1 10(30.3%), PMS2 8(24.2%) and MSH6 3(9.1%); Out of 10 MLH1 deficient cases, 6 (60%) were BRAF V600E mutant and 4 (40%) were BRAF-wild-type. We have found significance with medullary histological phenotype, poor histological grade and TILS. In our study, the frequency of MMR protein loss was found in 32% of patients of CRC. The loss was significantly associated with medullary phenotype, degree of differentiation and presence of tumor infiltrating lymphocytes (TILS).