Autor: |
Dedeurwaerdere F; Department of Pathology, AZ Delta General Hospital, Roeselare, Belgium., Claes KB; Center for Medical Genetics, Ghent University Hospital, Gent, Belgium.; Department of Biomolecular Medicine, Ghent University, Gent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent University, Gent, Belgium., Van Dorpe J; Department of Pathology, Ghent University Hospital, Gent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent University, Gent, Belgium., Rottiers I; Department of Pathology, Ghent University Hospital, Gent, Belgium., Van der Meulen J; Center for Medical Genetics, Ghent University Hospital, Gent, Belgium.; Cancer Research Institute Ghent (CRIG), Ghent University, Gent, Belgium.; Molecular Diagnostics, Ghent University Hospital, Gent, Belgium., Breyne J; Department of Laboratory Medicine, Department of Laboratory Medicine, AZ Delta General Hospital, AZ Delta General Hospital, Deltalaan 1, 8800, Roeselare, Belgium., Swaerts K; Department of Laboratory Medicine, Department of Laboratory Medicine, AZ Delta General Hospital, AZ Delta General Hospital, Deltalaan 1, 8800, Roeselare, Belgium., Martens G; Department of Laboratory Medicine, Department of Laboratory Medicine, AZ Delta General Hospital, AZ Delta General Hospital, Deltalaan 1, 8800, Roeselare, Belgium. geert.martens@azdelta.be.; Department of Biomolecular Medicine, Ghent University, Gent, Belgium. geert.martens@azdelta.be. |
Abstrakt: |
DNA mismatch repair deficiency (dMMR) testing is crucial for diagnosing Lynch syndrome and detection of microsatellite unstable (MSI) tumors eligible for immunotherapy. The aim of this study was to compare the relative diagnostic performance of three molecular MSI assays: polymerase chain reaction (PCR), MSI testing by Idylla 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 and PCR, and 0.93 for NGS. In colorectal cancers with tumor cell percentages ≥ 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 Idylla to 75% for NGS, corresponding to negative predictive values from 78 to 86%. PCR, Idylla 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. |