show Abstracthide Abstracthttps://www.preprints.org/manuscript/202410.0560/v1 Mismatch repair deficiency (MMRd) is clinically important as it can be indicative of Lynch syndrome (LS) and direct treatment with immune checkpoint inhibitors. All colorectal cancers (CRCs) and endometrial cancers (ECs) are screened in the UK to identify LS, primarily using immunohistochemistry (IHC) or Microsatellite Instability (MSI) testing, but concordance between these assays is lower in ECs. Here, we investigate this discordance by using an amplicon sequencing based MSI assay, the Newcastle MSI assay, to analyse 361 ECs from clinical trial cohorts with divergent concordance levels between IHC and standard MSI testing; the Ohio OCCPI and OPTEC trials, and the Manchester PETALS trial. We also analyse CRCs from both LS (n=35) and unselected (n=56) patient cohorts.