Universal tumor screening for lynch syndrome

Abstract

Lynch syndrome is estimated to affect 1 out of every 279 individuals worldwide. However, 95% of individuals with Lynch syndrome are not aware of their diagnosis. Therefore, it is important that we maximize all possible efforts to diagnose individuals with Lynch syndrome. Universal tumor screening is one approach that has been successful in helping to identify patients who might not have been referred for a genetics assessment otherwise. Universal tumor screening consists of testing the paraffin-embedded tumor from individuals with colorectal or endometrial cancer for features of deficient mismatch repair including microsatellite instability and/or absence of any of the four mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) using immunohistochemical (IHC) staining. Several professional organizations have recommended universal tumor screening of all newly diagnosed colorectal cancer patients at the time of diagnosis. Reasons for this recommendation are that patients whose tumors exhibit microsatellite instability (whether proven by MSI testing or extrapolated from abnormal IHC testing) have a better prognosis may need different treatment from those without microsatellite instability, and are more likely to have Lynch syndrome. Patients whose tumors exhibit MSI or have abnormal IHC without MLH1 methylation are suspicious for having Lynch syndrome and are candidates for genetic counseling and germline genetic testing. Best practices for implementing universal tumor screening have been explored.