MRC1 and neoplasm: A definitive diagnosis of LS is often obtained through a step-wise laboratory investigation including MMR functional analysis revealing DNA microsatellite instability (MSI) and/or immunohistochemical (IHC) lack of MMR protein expression in tumor tissue (often lack of both MLH1 and PMS2 or MSH2 and MSH6 as they form heterodimers) and the subsequent detection of a constitutional mutation, i.e., a pathogenic sequence variant, in any of the indicated MMR genes.