Timmerman S, Van Rompuy AS, Van Gorp T, et al. - In a consecutive series of patients (n = 108) who received a diagnosis of endometrial cancer (EC) at a tertiary referral center, researchers applied the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) and they used immunohistochemistry (IHC) for p53/mismatch repair protein expression and sequencing for Polymerase Epsilon Exonuclease Domain Mutations (POLE-EDM), to assign EC specimens to one of four molecular subgroups. A more thorough inquiry of Mismatch Repair Deficient (MMR-D) cases was performed to recognize underlying somatic or germline genetic defects. Among 33 patients with MMR-D on IHC (31%), MLH1 promotor hypermethylation as the likely cause of MMR-D was identified in 26. In six patients, a pathogenic germline mutation was detected in one of the mismatch repair genes: MSH6(n = 3), PMS2(n = 1), MLH1(n = 1) and MSH2 (n = 1). In this cohort, there was a high concordance between MMR-D and microsatellite instability. A large proportion of cases showing microsatellite instability was reported in cases of a genetic defect in the MMR genes. A hypermutation state, as noted in POLE EDM, did not lead to accompanied phenotypic alterations in microsatellite instability status. The efficiency of the ProMisE classification system, as well as its easy implementation, was proved in this study.