Improving the performance of polymerase chain reaction for microsatellite instability testing in endometrial cancer

Between 20% and 30% of endometrial cancer (EC) cases show mismatch repair deficiency (dMMR), and its characterisation is recommended in these tumours for molecular classification, screening of Lynch syndrome, and as a predictive biomarker for immunotherapy. The aim of this study was to explore two tests developed by Promega (OncoMate MSI Dx Analysis System and long mononucleotide repeat (LMR) microsatellite instability (MSI) analysis system). DNA from 126 EC tumours had been screened for MMR status by immunohistochemistry (IHC). Overall, 67 (53.2%) dMMRs and 59 (46.8%) proficient (pMMR) were included. The same cases were additionally explored for MMR genomic status, with 55 (43.7%) cases presenting an altered genomic pattern, and 69 (54.8%) with no genomic alterations. There were 71 (56.3%) microsatellite stability (MSS) cases for OncoMate and 69 (54.8%) for LMR, and 37 (29.4%) microsatellite instability (MSI) cases for OncoMate and 44 (34.9%) for LMR. Differences between the test assignments were significant (p < 0.001), with an increased proportion of correctly classified cases for the LMR assay, taking the IHC result as the reference. The respective sensitivity and specificity of the LMR assay was 95.5% and 68.1%, versus 86.5% and 53.5% for the OncoMate assay. In conclusion, the new LMR MSI Analysis System had a higher correlation with IHC, including cases that could be misdiagnosed due to minimal shifts, as well as higher sensitivity and specificity than the OncoMate panel. The best method regarding the use of dMMR/MSI as a response biomarker for immune checkpoint inhibitors requires further investigation.