Utilizing microsatellite instability and immunohistochemistry to clinically interpret a novel germline mismatch repair mutation of uncertain significance

Background Lynch syndrome (LS) is responsible for around 2-3% of all colorectal cancers [1]. Germline mutations within one of four mismatch repair (MMR) genes, MLH1, MSH2, MSH6, or PMS2, cause an increased risk in colorectal, endometrial, urinary tract, and other cancers. Tumor screening, by microsatellite instability (MSI) and immunohistochemistry (IHC) analysis, can be utilized prior to mutation analysis in order to streamline the testing process [2]. The following describes the use of MSI and IHC to aid in the clinical interpretation of a novel MMR mutation of uncertain significance and the direct impact on cancer detection.