Identification of Lynch Syndrome Carriers among Patients with Small Bowel Adenocarcinoma

Abstract

Simple SummarySmall bowel adenocarcinoma (SBA) is associated with Lynch syndrome (LS). This is the first study to evaluate the identification of LS patients based on mismatch repair deficiency (MMRd) tumor among SBA. The authors found a 21.3% prevalence of MMRd tumors and a 10.1% prevalence of LS. A germline mutation was identified in 60% of patients with a MMRd tumor. This data suggests that universal tumor MMR testing among SBA patients should be implemented for the identification of LS.Background: Small bowel adenocarcinoma (SBA) is a rare disease which can be associated with Lynch syndrome (LS). LS tumors are characterized by the presence of microsatellite instability (MSI) and/or the loss of mismatch repair (MMR) protein expression. In SBA, the frequency of MMR deficient (MMRd) tumors varies from 5% to 35%. This study aims to describe the prevalence of LS carriers among patients with MMRd small bowel adenocarcinomas. Methods: A multicenter retrospective study with identification and MMR testing of all consecutive SBA between 2004 and 2020 in a multicenter Spanish study. Demographical data, tumor characteristics, follow-up and survival information were collected. Germline testing was driven by identification of MMRd tumors. Results: A total of 94 individuals diagnosed with SBA were recruited. We observed 20 (21.3%) MMRd tumors. In 9/15 (60%) patients with MMRd tumors, a pathogenic variant was identified (three MLH1, four MSH2, one MSH6 and one PMS2). Accordingly, the prevalence of LS among all SBA cases was 10.1%. Conclusions: More than one-fifth of SBA display MMRd and in more than a half is due to LS. Our data supports the implementation of universal MMR tumor testing among SBA for the identification of LS families.