Algorithm for testing of endometrial adenocarcinomas for MMR deficiency. A 2-antibody approach utilizing MSH6 and PMS2 as preliminary screening with subsequent MSH2 or MLH1 IHC for cases that show loss of MSH6 or PMS2 can also be performed.
*If strong clinical suspicion for LS, consider MLH1 promoter methylation analysis of non-neoplastic tissue/peripheral blood to evaluate for germline epigenetic MLH1 promoter methylation.
**If MSH2 and MSH6 unmutated, consider LS EPCAM, sequencing and deletion/duplication.