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

Ana Velasco; Fatma Tokat; Jesper Bonde; Nicola Trim; Elisabeth Bauer; Adam Meeney; Wendy de Leng; George Chong; Véronique Dalstein; Lorand L. Kis; Jon A. Lorentzen; Snjezana Tomić; Keeley Thwaites; Martina Putzová; Astrid Birnbaum; Romena Qazi; Vanessa Primmer; Barbara Dockhorn-Dworniczak; Javier Hernández-Losa; Fernando A. Soares; Asaf A. Gertler; Michal Kalman; Chris Wong; Dirce M. Carraro; Ana C. Sousa; Rui M. Reis; Stephen B. Fox; Matteo Fassan; Marie Brevet; Sabine Merkelbach-Bruse; Richard Colling; Elizabeth Soilleux; Ryan Yee Wei Teo; Nicky D’Haene; Serge Nolet; Ari Ristimäki; Timo Väisänen; Caroline Chapusot; Afsaneh Soruri; Tina Unger; Johanna Wecgowiec; Michele Biscuola; Milo Frattini; Anna Long; Paulo V. Campregher; Xavier Matias-Guiu

doi:10.1007/s00428-020-02962-x

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

Ana Velasco
, Fatma Tokat
, Jesper Bonde
, Nicola Trim
, Elisabeth Bauer
, Adam Meeney
, Wendy de Leng
, George Chong
, Véronique Dalstein
, Lorand L. Kis
, Jon A. Lorentzen
, Snjezana Tomić
, Keeley Thwaites
, Martina Putzová
, Astrid Birnbaum
, Romena Qazi
, Vanessa Primmer
, Barbara Dockhorn-Dworniczak
, Javier Hernández-Losa
, Fernando A. Soares

Asaf A. Gertler, Michal Kalman, Chris Wong, Dirce M. Carraro, Ana C. Sousa, Rui M. Reis, Stephen B. Fox, Matteo Fassan, Marie Brevet, Sabine Merkelbach-Bruse, Richard Colling, Elizabeth Soilleux, Ryan Yee Wei Teo, Nicky D’Haene, Serge Nolet, Ari Ristimäki, Timo Väisänen, Caroline Chapusot, Afsaneh Soruri, Tina Unger, Johanna Wecgowiec, Michele Biscuola, Milo Frattini, Anna Long, Paulo V. Campregher, Xavier Matias-Guiu

University of Lleida
Acibadem Mehmet Ali Aydinlar Universitesi
University of Copenhagen
University Hospitals Birmingham NHS Foundation Trust
Städtischen Klinikum Karlsruhe
Sheffield Teaching Hospitals NHS Foundation Trust
Utrecht University
McGill University
CHU de Reims
Karolinska Institutet
University of Oslo
Split University Hospital
Barking, Havering and Redbridge University Hospitals NHS Trust
Bioptická laboratoř s.r.o.
Charles University
LF UK
Institute of Pathology
Shaukat Khanum Memorial Cancer Hospital and Research Centre
Pathologisch-Bakteriologisches Institut Kaiser-Franz-Josef-Spital
Zentrum für Pathologie Kempten-Allgäu
University Hospital Vall d’ Hebron
Centro de Investigación Biomédica en Red
Anatomia Patológica Rede D’Or
Hadassah University Medical Centre
Comenius University
Martin’s Biopsy Center Ltd.
Hong Kong Special Administrative Region of the People’s Republic of China
A.C.Camargo Cancer Center
S.A.
Hospital de Câncer de Barretos
University of Minho
Peter Maccallum Cancer Centre
University of Padua
Universite Claude Bernard Lyon 1
University of Cologne
University of Oxford
University of Cambridge
Tan Tock Seng Hospital
Université libre de Bruxelles
University of Montreal
University of Helsinki
University of Oulu
Université de Bourgogne
Institut für Pathologie und Molekularpathologie
Leipzig University
Evangelisches Krankenhaus BETHESDA Zu Duisburg GmbH
Hospital Universitario Virgen del Rocio
Institute of Pathology
Newcastle upon Tyne Hospitals NHS Foundation Trust
Hospital Israelita Albert Einstein

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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.

Original language	English
Pages (from-to)	851-863
Number of pages	13
Journal	Virchows Archiv
Volume	478
Issue number	5
DOIs	https://doi.org/10.1007/s00428-020-02962-x
State	Published - May 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

Funding

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.”

Funders
DIMED
Department of Cellular Pathology
Dept. of Pathology Acıbadem Mehmet Ali Aydınlar University
Erasme University Hospital
Gustavo Noriz Berardinelli and Iara Santana
Hospices Civils de Lyon, Université Lyon
Hospital Universitari Arnau de Vilanova
Institut für Pathologie
Tan Tock Seng Hospital
Hadassah Medical Organization
University Hospitals Birmingham NHS Foundation Trust
Department of Medicine, Georgetown University
Università degli Studi di Padova
Vrije Universiteit Brussel
Oxford University Hospitals NHS Foundation Trust
Fundació Institut de Recerca Hospital Universitari Vall d’Hebron

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Colorectal cancer
FFPE clinical tissue samples
Idylla™ MSI assay
Microsatellite instability
Multi-center study

Access to Document

10.1007/s00428-020-02962-x

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Velasco, A., Tokat, F., Bonde, J., Trim, N., Bauer, E., Meeney, A., de Leng, W., Chong, G., Dalstein, V., Kis, L. L., Lorentzen, J. A., Tomić, S., Thwaites, K., Putzová, M., Birnbaum, A., Qazi, R., Primmer, V., Dockhorn-Dworniczak, B., Hernández-Losa, J., ... Matias-Guiu, X. (2021). 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. Virchows Archiv, 478(5), 851-863. https://doi.org/10.1007/s00428-020-02962-x

@article{84ff09069f3943798a60d32ab9a98305,

title = "Multi-center real-world comparison of the fully automated Idylla{\texttrademark} microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer",

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{\texttrademark} 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{\texttrademark} testing on a total of 1301 archived colorectal cancer formalin-fixed, paraffin-embedded (FFPE) tissue sections and compared Idylla{\texttrademark} results against available results from routine diagnostic testing in those sites. MSI mutations detected with the Idylla{\texttrademark} 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{\texttrademark} 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{\texttrademark} 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{\texttrademark} MSI Assay and routine tests.",

keywords = "Colorectal cancer, FFPE clinical tissue samples, Idylla{\texttrademark} MSI assay, Microsatellite instability, Multi-center study",

author = "Ana Velasco and Fatma Tokat and Jesper Bonde and Nicola Trim and Elisabeth Bauer and Adam Meeney and \{de Leng\}, Wendy and George Chong and V{\'e}ronique Dalstein and Kis, \{Lorand L.\} and Lorentzen, \{Jon A.\} and Snjezana Tomi{\'c} and Keeley Thwaites and Martina Putzov{\'a} and Astrid Birnbaum and Romena Qazi and Vanessa Primmer and Barbara Dockhorn-Dworniczak and Javier Hern{\'a}ndez-Losa and Soares, \{Fernando A.\} and Gertler, \{Asaf A.\} and Michal Kalman and Chris Wong and Carraro, \{Dirce M.\} and Sousa, \{Ana C.\} and Reis, \{Rui M.\} and Fox, \{Stephen B.\} and Matteo Fassan and Marie Brevet and Sabine Merkelbach-Bruse and Richard Colling and Elizabeth Soilleux and Teo, \{Ryan Yee Wei\} and Nicky D{\textquoteright}Haene and Serge Nolet and Ari Ristim{\"a}ki and Timo V{\"a}is{\"a}nen and Caroline Chapusot and Afsaneh Soruri and Tina Unger and Johanna Wecgowiec and Michele Biscuola and Milo Frattini and Anna Long and Campregher, \{Paulo V.\} and Xavier Matias-Guiu",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2021",

month = may,

doi = "10.1007/s00428-020-02962-x",

language = "אנגלית",

volume = "478",

pages = "851--863",

journal = "Virchows Archiv",

issn = "0945-6317",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "5",

}

Velasco, A, Tokat, F, Bonde, J, Trim, N, Bauer, E, Meeney, A, de Leng, W, Chong, G, Dalstein, V, Kis, LL, Lorentzen, JA, Tomić, S, Thwaites, K, Putzová, M, Birnbaum, A, Qazi, R, Primmer, V, Dockhorn-Dworniczak, B, Hernández-Losa, J, Soares, FA, Gertler, AA, Kalman, M, Wong, C, Carraro, DM, Sousa, AC, Reis, RM, Fox, SB, Fassan, M, Brevet, M, Merkelbach-Bruse, S, Colling, R, Soilleux, E, Teo, RYW, D’Haene, N, Nolet, S, Ristimäki, A, Väisänen, T, Chapusot, C, Soruri, A, Unger, T, Wecgowiec, J, Biscuola, M, Frattini, M, Long, A, Campregher, PV & Matias-Guiu, X 2021, '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', Virchows Archiv, vol. 478, no. 5, pp. 851-863. https://doi.org/10.1007/s00428-020-02962-x

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. / Velasco, Ana; Tokat, Fatma; Bonde, Jesper et al.
In: Virchows Archiv, Vol. 478, No. 5, 05.2021, p. 851-863.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Velasco, Ana

AU - Tokat, Fatma

AU - Bonde, Jesper

AU - Trim, Nicola

AU - Bauer, Elisabeth

AU - Meeney, Adam

AU - de Leng, Wendy

AU - Chong, George

AU - Dalstein, Véronique

AU - Kis, Lorand L.

AU - Lorentzen, Jon A.

AU - Tomić, Snjezana

AU - Thwaites, Keeley

AU - Putzová, Martina

AU - Birnbaum, Astrid

AU - Qazi, Romena

AU - Primmer, Vanessa

AU - Dockhorn-Dworniczak, Barbara

AU - Hernández-Losa, Javier

AU - Soares, Fernando A.

AU - Gertler, Asaf A.

AU - Kalman, Michal

AU - Wong, Chris

AU - Carraro, Dirce M.

AU - Sousa, Ana C.

AU - Reis, Rui M.

AU - Fox, Stephen B.

AU - Fassan, Matteo

AU - Brevet, Marie

AU - Merkelbach-Bruse, Sabine

AU - Colling, Richard

AU - Soilleux, Elizabeth

AU - Teo, Ryan Yee Wei

AU - D’Haene, Nicky

AU - Nolet, Serge

AU - Ristimäki, Ari

AU - Väisänen, Timo

AU - Chapusot, Caroline

AU - Soruri, Afsaneh

AU - Unger, Tina

AU - Wecgowiec, Johanna

AU - Biscuola, Michele

AU - Frattini, Milo

AU - Long, Anna

AU - Campregher, Paulo V.

AU - Matias-Guiu, Xavier

PY - 2021/5

Y1 - 2021/5

N2 - 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.

AB - 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.

KW - Colorectal cancer

KW - FFPE clinical tissue samples

KW - Idylla™ MSI assay

KW - Microsatellite instability

KW - Multi-center study

UR - https://www.scopus.com/pages/publications/85095824973

U2 - 10.1007/s00428-020-02962-x

DO - 10.1007/s00428-020-02962-x

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 33170334

AN - SCOPUS:85095824973

SN - 0945-6317

VL - 478

SP - 851

EP - 863

JO - Virchows Archiv

JF - Virchows Archiv

IS - 5

ER -

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

Abstract

Bibliographical note

Funding

UN SDGs

Keywords

Access to Document

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