Multi-center real-world comparison of the fully automated IdyllaTM microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer
Abstrakt
Microsatellite instability (MSI) is present in 15-20% of primary colorectal cancers. MSI status is assessed to detect Lynch syndrome, guide adjuvant chemotherapy, determine prognosis, and use as a companion test for checkpoint blockade inhibitors.
Traditionally, MSI status is determined by immunohistochemistry or molecular methods. The IdyllaTM MSI Assay is a fully automated molecular method (including automated result interpretation), using seven novel MSI biomarkers (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A, SULF2) and not requiring matched normal tissue.
In this real-world global study, 44 clinical centers performed IdyllaTM testing on a total of 1301 archived colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissue sections and compared IdyllaTM results against available results from routine diagnostic testing in those sites. MSI mutations detected with the IdyllaTM MSI Assay were equally distributed over the seven biomarkers, and 84.48% of the MSI-high samples had >= 5 mutated biomarkers, while 98.25% of the microsatellite-stable samples had zero mutated biomarkers.
The concordance level between the IdyllaTM MSI Assay and immunohistochemistry was 96.39% (988/1025); 17/37 discordant samples were found to be concordant when a third method was used. Compared with routine molecular methods, the concordance level was 98.01% (789/805); third-method analysis found concordance for 8/16 discordant samples.
The failure rate of the IdyllaTM MSI Assay (0.23%; 3/1301) was lower than that of referenced immunohistochemistry (4.37%; 47/1075) or molecular assays (0.86%; 7/812). In conclusion, lower failure rates and high concordance levels were found between the IdyllaTM MSI Assay and routine tests.