Fig. 1

Overview of study design. Schema presenting the study inclusion criteria, the breakdown of the clinical MMR IHC results, the testing assays applied and the final study results, separated by tissue type and combined. SLS suspected Lynch syndrome, CRC colorectal cancer, EC endometrial cancer, SST sebaceous skin tumor, MMR DNA mismatch repair, IHC immunohistochemistry, dMMR-PriEpi primary epimutation, dMMR-MLH1me positive MLH1 methylation, dMMR-DS double somatic mutations, pMMR DNA mismatch repair proficient, dMMR-LS Lynch syndrome, dMMR-SS single somatic mutation. ^aSLS criteria: individuals diagnosed with a DNA mismatch repair deficient CRC, EC and/or SST with previous negative testing results. ^bBreakdown of clinical MMR IHC results when first entering the study. ^cdMMR with a germline pathogenic variant identified (Lynch syndrome, “dMMR-LS”). ^ddMMR with tumor MLH1 methylation (MLH1 methylated, “dMMR-MLH1me”). ^edMMR with tumor and blood MLH1 methylation (primary epimutation, “dMMR-PriEpi”). ^fdMMR with double somatic MMR variants in the same MMR gene (double somatic mutation, “dMMR-DS”). ^gdMMR with a single somatic MMR variant (single somatic mutation, “dMMR-SS”). ^hdMMR with no germline or somatic variants (suspected Lynch syndrome, “dMMR-SLS”). ⁱpMMR tumors with neither germline or somatic mutations nor hypermethylation of the MLH1 gene (DNA mismatch repair proficient, “pMMR”)