Prevalence and Molecular Characterization of Defective DNA Mismatch Repair in Small-bowel Carcinoma in a Japanese Hospital-based Population

Abstract

Objectives: To investigate the prevalence and molecular characteristics of defective DNA mismatch repair (dMMR) in small-bowel carcinoma (SBC) in a Japanese-hospital population. Methods: Immunohistochemistry was performed to evaluate the expression of MMR proteins (MLH1, MSH2, MSH6, and PMS2) in formalin-fixed paraffin-embedded sections prepared from surgically resected primary SBCs from 30 patients during March 2002 to March 2017. Genetic testing for Lynch syndrome was performed in patients who demonstrated MMR protein loss. Results: Two of 30 patients (6.7%) demonstrated concomitant loss of MSH2/MSH6 protein expression. Further genetic testing identified a pathogenic MSH2 variant in one of these patients. Conclusions: The prevalence of dMMR SBCs in a Japanese hospital-based population seems lower than that reported in previous studies. To determine whether dMMR SBCs might be strongly linked to Lynch syndrome, there is a need for further investigation with a larger sample size.