Lynch Syndrome in context of the updated German S3 guideline Colorectal Cancer - Implementation of universal MMR/MSI-testing.

Abstract

Background: With 1:280 carriers, Lynch Syndrome (LS) is the most prevalent tumor predisposition syndrome and the most important cause for hereditary colorectal cancer (CRC). Tumors from affected individuals usually present with a deficient expression of mismatch repair proteins (MMR) leading to a high microsatellite instability (MSI).

Summary: With the update of the German S3-guideline CRC, universal MSI/MMR testing is going to be implemented, thus leading to a fundamental change in detection of patients belonging to the risk group of LS. From now on, there is a strong recommendation for performing MMR/MSI-diagnostics for every CRC-patient regardless of tumor stage not only in the surgical specimen but in the initial tumor biopsy. The subsequent algorithm for germline mutational testing is simplified. For CRC patients under the age of 50 years, multigene panel testing is recommended regardless of MSI/MMR status. Therapeutic considerations leading to MMR/MSI testing in other entities should warrant the same diagnostic approach. Surveillance measures are individualized especially regarding upper and lower GI endoscopy considering mutational status.

Key messages: Universal MMR/MSI Testing is recommended for any CRC patient in the tumor biopsy. Subsequent germline mutational testing should be performed automatically in case of suspicious findings. The detection rate of LS carriers thus will be improved compared to current clinical criteria.