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.

Anatomia Patológica Rede D'Or São Paulo SP Brazil

Bioptická laboratoř s r o Laboratory of Molecular Genetics Plzeň Czech Republic

Cellular Pathology Newcastle Upon Tyne Hospitals NHS Foundation Trust Newcastle upon Tyne UK

Département de Pathologie et Biologie Cellulaire Université de Montréal Montreal Québec Canada

Department of Clinical Pathology and Cytology Karolinska University Hospital Stockholm Sweden

Department of Pathologic Anatomy Jessenius Faculty of Medicine Comenius University in Bratislava Martin Slovak Republic

Department of Pathology Acıbadem Mehmet Ali Aydınlar University Istanbul Turkey

Department of Pathology Erasme Hospital Université Libre de Bruxelles Brussels Belgium

Department of Pathology Forensic Medicine and Cytology University Hospital Split Split Croatia

Department of Pathology Hadassah Medical Center Jerusalem Israel

Department of Pathology Hospices Civils de Lyon Université Lyon 1 Bron France and Cypath Villeurbanne France

Department of Pathology Hospital Universitari Vall d'Hebron Barcelona Spain

Department of Pathology Molecular Pathology Laboratory Hospital Universitario Virgen del Rocío IBIS Seville Spain

Department of Pathology Research Programs Unit and HUSLAB University of Helsinki and Helsinki University Hospital Helsinki Finland

Department of Pathology Shaukat Khanum Memorial Cancer Hospital and Research Centre Johr Town Lahore Pakistan

Department of Pathology Tan Tock Seng Hospital Novena Republic of Singapore

Department of Pathology University Medical Center Utrecht Utrecht The Netherlands

Department of Pathology University of Cambridge Cambridge UK

Departments of Pathology and Molecular Genetics Hospital U Arnau de Vilanova and Hospital U de Bellvitge University of Lleida IRBLLEIDA IDIBELL CIBERONC Av Alcalde Rovira Roure 80 25198 Lleida Spain

GenoMed Diagnósticos de Medicina Molecular SA Lisbon Portugal

Genomics and Molecular Biology Group International Research Center CIPE A C Camargo Cancer Center São Paulo SP Brazil

Histopathology Department Barking Havering and Redbridge University Hospitals NHS Trust Queen's Hospital Romford UK

Hong Kong Molecular Pathology Diagnostic Centre Hong Kong Special Administrative Region of the People's Republic of China Hong Kong People's Republic of China

Hospital Israelita Albert Einstein São Paulo Brazil

ICVS 3B's PT Government Associate Laboratory Braga Guimarães Portugal

Institut für Pathologie Evangelisches Krankenhaus BETHESDA Zu Duisburg GmbH Duisburg Germany

Institut für Pathologie und Molekularpathologie Pforzheim Germany

Institut für Pathologie University of Leipzig Leipzig Germany

Institute of Pathology Dessau Germany

Institute of Pathology University Hospital Cologne Cologne Germany

Laboratoire de Biopathologie Unité INSERM UMR S 1250 CHU Reims Reims France

Laboratory of Molecular Pathology Institute of Pathology Locarno Switzerland

LF UK Plzeň Czech Republic

Life and Health Sciences Research Institute School of Medicine University of Minho Braga Portugal

Martin's Biopsy Center Ltd Martin Slovak Republic

Molecular Oncology Research Center Barretos Cancer Hospital Barretos SP Brazil

Molecular Pathology Centre Jewish General Hospital McGill University Montreal Quebec Canada

Molecular Pathology Diagnostic Service University Hospitals Birmingham NHS Foundation Trust Birmingham UK

Molecular Pathology Laboratory Department of Pathology afs 134 Hvidovre Hospital Hvidovre Denmark

Molecular Pathology Unit Department of Pathology Oslo University Hospital Oslo Norway

Nuffield Department of Surgical Sciences University of Oxford Oxford UK

Ophthalmic Pathology Laboratory Histopathology Royal Hallamshire Hospital Glossop Road Sheffield UK

Oulu University Hospital and Department of Pathology Cancer and Translational Medicine Research Unit University of Oulu Oulu Finland

Pathologisch Bakteriologisches Institut Kaiser Franz Josef Spital Vienna Austria

Pathology Peter MacCallum Cancer Centre and University of Melbourne Vic Australia

Platform of Somatic Oncology of Burgundy CHU Dijon France

Spanish Biomedical Research Network Centre in Oncology Madrid Spain

Städtisches Klinikum Karlsruhe gGmbH Institut für Pathologie Karlsruhe Germany

Surgical Pathology Unit Department of Medicine University of Padua Padua Italy

ÚBLG FN Motol Praha Czech Republic

Zentrum für Pathologie Kempten Allgäu Kempten Germany

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