DNA mismatch repair deficiency (dMMR) testing is crucial for diagnosing Lynch syndrome and detection of microsatellite unstable (MSI) tumors eligible for immunotherapy.
In this study, we compared the diagnostic performance of three molecular MSI assays: polymerase chain reaction (PCR), MSI testing by Idylla TM and next-generation-sequencing (NGS) on 49 tumor samples (28 colorectal and 21 endometrial adenocarcinomas) versus immunohistochemistry (IHC). Discrepancies were investigated by MLH1 methylation analysis and integrated with germline results if available.
Overall, the molecular assays achieved equivalent diagnostic performance for MSI detection with area under the ROC curves (AUC) of respectively 0.91 for Idylla TM and PCR, and 0.93 for NGS. In colorectal cancers with tumor cell percentage ≥ 30% all three molecular assays achieved 100% sensitivity and specificity (AUC = 1) versus IHC. Also, in endometrial cancers, all three molecular assays showed equivalent diagnostic performance, albeit at a clearly lower sensitivity ranging from 58% for IdyllaTM to 75% for NGS, corresponding to negative predictive values from 78% to 86%.
PCR, IdyllaTM and NGS show similar diagnostic performance for dMMR detection in colorectal and endometrial cancers. Molecular MSI analysis has lower sensitivity for dMMR detection in endometrial cancer indicating that combined use of both IHC and molecular methods is recommended.
Clinical Trial Number/IRB: B1172020000040, Ethical Committee, AZ Delta General Hospital