Update on immunohistochemistry to identify colorectal tumours with deficient DNA mismatch repair function

Abstract

DNA mismatch repair (MMR) protein immunohistochemistry (IHC) is useful to screen for Lynch syndrome (LS), as well as to identify the larger population of patients with sporadic MMR deficiency (dMMR). In this review, in addition to briefly discussing the molecular genetic basis and phenotype of LS and sporadic dMMR tumours, the universal LS screening program employed at the University of Iowa Hospitals and Clinics, the frequency of dMMR in adenomas from LS patients, and potential pitfalls in the interpretation of MMR IHC, several recent discoveries that should impact testing will be covered, namely: 1. EPCAM deletion as a cause of MSH2 deficiency, 2. availability of BRAFV600E mutation-specific IHC, and especially 3. Lynch-like syndrome (i.e., patients with dMMR tumours in whom a sporadic tumour due to MLH1 promoter methylation has been excluded and an MMR germline mutation is not detected).