Multi-center real-world comparison of the fully automated Idylla (TM) microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer
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; Matias-Guiu, Xavier
(2021) Virchows Archives, volume 478, issue 5, pp. 851 - 863
(Article)
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
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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.
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Keywords: Colorectal cancer, FFPE clinical tissue samples, Idylla™ MSI assay, Microsatellite instability, Multi-center study, Idylla™, MSI assay, Molecular Biology, Pathology and Forensic Medicine, Cell Biology, Journal Article
ISSN: 0945-6317
Publisher: Springer Verlag
Note: Funding Information: The Idylla™ MSI assay cartridges used in the current study were kindly provided by Biocartis (Mechelen, Belgium), and Biocartis has seen the manuscript prior to submission. The authors thank Luc Geeraert (Bench to Pen - Scientific Writing) for his editorial and writing support, Prof. Umit Ince and Prof. Sibel Erdamar (both from the Dept. of Pathology Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey), Prof. M. Cengiz Yakıcıer (Dept. of Molecular Bıology and Genetics Acıbadem Mehmet Ali Aydınlar University, Istanbul, Turkey), Dr. Matthew J. Smith (Molecular Pathology Diagnostic Service, University Hospitals Birmingham Foundation Trust, UK), Prof. Dr. Med. Thomas Rüdiger (Städtisches Klinikum Karlsruhe gGmbH, Institut für Pathologie, Karlsruhe, Germany) for his support, Stephen Rodgers (Barking, Havering and Redbridge University Hospitals NHS Trust, Queen’s Hospital), Dr. Karsten Neumann (Molecular Biologist, Head of the Molecular Diagnostics Section, Institute of Pathology, Dessau, Germany) for organizing the trial and discussion of results, Rosa Somoza (Department of Pathology, Hospital Universitari Vall d’Hebron, Barcelona, Spain) for her technical support, Dolors Cuevas (Department of Pathology, Hospital Universitari Arnau de Vilanova, Lleida, Spain), Dr. Ariel Erental (Department of Pathology, Hadassah Medical Center, Jerusalem, Israel) for performing hands-on tests, Prof Chuah Khoon Leong (Head of Department of Pathology, Tan Tock Seng Hospital, Novena, Republic of Singapore) for his expertise in diagnosing and evaluating the cases used for this study, Gustavo Noriz Berardinelli and Iara Santana (both Barretos Cancer Hospital, Barretos, SP, Brazil), Dr. Giada Munari (Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy) for her technical support, Carole Ferraro-Peyret (Department of Pathology, Hospices Civils de Lyon, Université Lyon 1, Bron, France) for her active participation in data collection and molecular routine analysis, the Department of Cellular Pathology (Oxford University Hospitals NHS Foundation Trust, Oxford, UK) for providing space for Idylla testing and the Cambridge Human Research Tissue Bank (Addenbrooke’s Hospital, Cambridge, UK) for preparing and providing tissue, Prof. Dr. Med. Isabelle Salmon (Laboratory of Pathology, Erasme University Hospital, Free University of Brussels (ULB), Brussels, Belgium) for her support, Claude Van Campenhout (Laboratory of Pathology, Erasme University Hospital, Free University of Brussels (ULB), Brussels, Belgium) for her technical support, and Dr. Med. Pierre Heiman and Dr. Hakim El Housni (Laboratory of Genetics, Erasme University Hospital, Free University of Brussels (ULB), Brussels, Belgium) for their support. “The study benefited from samples/data from Northern Finland Biobank Borealis, Oulu, Finland. www.ppshp.fi/biopankki.” Publisher Copyright: © 2020, The Author(s).
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