Screening for Lynch Syndrome in Cases with Colorectal Carcinoma from Mashhad

Lynch Syndrome (LS) is a genetically inherited autosomal disorder that increases the risk of many types of cancer, especially colorectal cancer (CRC). Identifying these subjects improves morbidity and mortality. We aimed to assess the prevalence of LS with both clinical criteria and universal strategy in Mashhad, Iran.

In this retrospective study, we screened 322 patients with CRC between 2013 and 2016 in Mashhad, Iran. CRCs were screened based on Amsterdam II criteria, revised Bethesda guideline, and universal strategy. Information regarding the clinical criteria was obtained by interviewing the patients or, their families. Tumors were screened by pathologists with IHC staining of four Mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, and PMS2). Tumors with absent IHC staining of MLH1 were tested for BRAF mutations to exclude sporadic CRCs.

Of 322 CRCs, 33 cases were found to be deficient-MMR; 22 of these had concurrent loss of MLH1 and PMS2, followed by concurrent loss of MSH2 and MSH6 in 8 CRCs. Twenty-two cases with a loss of MLH1 underwent testing for the BRAF mutation, 4 of which were recognized as a positive BRAF mutation. Finally, 29 CRCs were found as being positive screen for LS. Poor sensitivity (21.74%) was found for the Amsterdam II criteria and a poor positive predictive value (15.39%) for the revised Bethesda.

Application of clinical criteria may not be effective enough to identify LS and at least 2-antibody panel (PMS2, MSH6) should be conducted for newly diagnosed CRCs.