Christakis AG, et al. - Researchers tested targeted cancer next-generation sequencing for its accuracy in detecting microsatellite instability in upper gastrointestinal tract cancers and screen for patients with Lynch syndrome. They examined a cohort of 645 upper gastrointestinal tract cancers. In 3.6% (23/645) of upper gastrointestinal tract cancers, microsatellite instability was detected by sequencing, these cases included 28% (8/29) of small intestinal and 9% (9/97) of gastric carcinomas. Microsatellite instability was present in 20 cancers, of which, 19 showed loss of MLH1, PMS2, MSH2, or MSH6 expression, and one cancer was indeterminate by IHC. Expression of all mismatch repair proteins was retained in 52 control cancers. The presence of pathogenic germline variants in 1.1% (7/645) of patients was found using targeted sequencing as the initial screening test, resulting in confirmation of a diagnosis of Lynch syndrome. Overall, findings revealed the accuracy of targeted cancer next-generation sequencing as a first-line test to identify microsatellite instability in upper gastrointestinal tract cancers.