1. Multi-center real-world comparison of the fully automated Idylla™ microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer
- Author
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Velasco, Ana, Tokat, Fatma, Bonde, Jesper, Trim, Nicola, Bauer, Elisabeth, Meeney, Adam, De Leng, Wendy, Chong, George, Dalstein, Véronique, Kis, Lorand L, Lorentzen, Jon A, Tomić, Snjezana, Thwaites, Keeley, Putzová, Martina, Birnbaum, Astrid, Qazi, Romena, Primmer, Vanessa, Dockhorn-Dworniczak, Barbara, Hernández-Losa, Javier, Soares, Fernando A, Gertler, Asaf A, Kalman, Michal, Wong, Chris, Carraro, Dirce M, Sousa, Ana C, Reis, Rui M, Fox, Stephen B, Fassan, Matteo, Brevet, Marie, Merkelbach-Bruse, Sabine, Colling, Richard, Soilleux, Elizabeth, Teo, Ryan Yee Wei, D'Haene, Nicky, Nolet, Serge, Ristimäki, Ari, Väisänen, Timo, Chapusot, Caroline, Soruri, Afsaneh, Unger, Tina, Wecgowiec, Johanna, Biscuola, Michele, Frattini, Milo, Long, Anna, Campregher, Paulo V, and Matias-Guiu, Xavier
- Subjects
Automation, Laboratory ,Paraffin Embedding ,Tissue Fixation ,DNA Mutational Analysis ,Idylla™ MSI assay ,Reproducibility of Results ,Colorectal cancer ,Immunohistochemistry ,digestive system diseases ,Multi-center study ,3. Good health ,Fixatives ,Predictive Value of Tests ,Formaldehyde ,Mutation ,Microsatellite instability ,Biomarkers, Tumor ,Humans ,Colorectal Neoplasms ,neoplasms ,FFPE clinical tissue samples - Abstract
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 Idylla™ 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 Idylla™ testing on a total of 1301 archived colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissue sections and compared Idylla™ results against available results from routine diagnostic testing in those sites. MSI mutations detected with the Idylla™ 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 Idylla™ 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 Idylla™ 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 Idylla™ MSI Assay and routine tests.