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Published in: Virchows Archiv 2/2021

Open Access 01-08-2021 | Polymerase Chain Reaction | Original Article

Evaluation of a worldwide EQA scheme for complex clonality analysis of clinical lymphoproliferative cases demonstrates a learning effect

Authors: Cleo Keppens, Elke Boone, Paula Gameiro, Véronique Tack, Elisabeth Moreau, Elizabeth Hodges, Paul Evans, Monika Brüggemann, Ian Carter, Dido Lenze, Maria Eugenia Sarasquete, Markus Möbs, Hongxiang Liu, Elisabeth M. C. Dequeker, Patricia J. T. A. Groenen

Published in: Virchows Archiv | Issue 2/2021

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Abstract

Clonality analysis of immunoglobulin (IG) or T-cell receptor (TR) gene rearrangements is routine practice to assist diagnosis of lymphoid malignancies. Participation in external quality assessment (EQA) aids laboratories in identifying systematic shortcomings. The aim of this study was to evaluate laboratories’ improvement in IG/TR analysis and interpretation during five EQA rounds between 2014 and 2018. Each year, participants received a total of five cases for IG and five cases for TR testing. Paper-based cases were included for analysis of the final molecular conclusion that should be interpreted based on the integration of the individual PCR results. Wet cases were distributed for analysis of their routine protocol as well as evaluation of the final molecular conclusion. In total, 94.9% (506/533) of wet tests and 97.9% (829/847) of paper tests were correctly analyzed for IG, and 96.8% (507/524) wet tests and 93.2% (765/821) paper tests were correctly analyzed for TR. Analysis scores significantly improved when laboratories participated to more EQA rounds (p=0.001). Overall performance was significantly lower (p=0.008) for non-EuroClonality laboratories (95% for IG and 93% for TR) compared to EuroClonality laboratories (99% for IG and 97% for TR). The difference was not related to the EQA scheme year, anatomic origin of the sample, or final clinical diagnosis. This evaluation showed that repeated EQA participation helps to reduce performance differences between laboratories (EuroClonality versus non-EuroClonality) and between sample types (paper versus wet). The difficulties in interpreting oligoclonal cases highlighted the need for continued education by meetings and EQA schemes.
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Literature
3.
go back to reference Van Dongen JJ, Langerak AW, Bruggemann M et al (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 17:2257–2317. https://doi.org/10.1038/sj.leu.2403202CrossRefPubMed Van Dongen JJ, Langerak AW, Bruggemann M et al (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 17:2257–2317. https://​doi.​org/​10.​1038/​sj.​leu.​2403202CrossRefPubMed
4.
go back to reference Brüggemann M, White H, Gaulard P, Garcia-Sanz R, Gameiro P, Oeschger S, Jasani B, Ott M, Delsol G, Orfao A, Tiemann M, Herbst H, Langerak AW, Spaargaren M, Moreau E, Groenen PJTA, Sambade C, Foroni L, Carter GI, Hummel M, Bastard C, Davi F, Delfau-Larue MH, Kneba M, van Dongen JJM, Beldjord K, Molina TJ (2007) Powerful strategy for PCR-based clonality assessment in T-cell malignancies. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia 21:215–221. https://doi.org/10.1038/sj.leu.2404481CrossRefPubMed Brüggemann M, White H, Gaulard P, Garcia-Sanz R, Gameiro P, Oeschger S, Jasani B, Ott M, Delsol G, Orfao A, Tiemann M, Herbst H, Langerak AW, Spaargaren M, Moreau E, Groenen PJTA, Sambade C, Foroni L, Carter GI, Hummel M, Bastard C, Davi F, Delfau-Larue MH, Kneba M, van Dongen JJM, Beldjord K, Molina TJ (2007) Powerful strategy for PCR-based clonality assessment in T-cell malignancies. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia 21:215–221. https://​doi.​org/​10.​1038/​sj.​leu.​2404481CrossRefPubMed
5.
go back to reference Evans PAS, Pott C, Groenen PJTA, Salles G, Davi F, Berger F, Garcia JF, van Krieken JHJM, Pals S, Kluin P, Schuuring E, Spaargaren M, Boone E, González D, Martinez B, Villuendas R, Gameiro P, Diss TC, Mills K, Morgan GJ, Carter GI, Milner BJ, Pearson D, Hummel M, Jung W, Ott M, Canioni D, Beldjord K, Bastard C, Delfau-Larue MH, van Dongen JJM, Molina TJ, Cabeçadas J (2007) Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4- CT98-3936. Leukemia 21:207–214. https://doi.org/10.1038/sj.leu.2404479CrossRefPubMed Evans PAS, Pott C, Groenen PJTA, Salles G, Davi F, Berger F, Garcia JF, van Krieken JHJM, Pals S, Kluin P, Schuuring E, Spaargaren M, Boone E, González D, Martinez B, Villuendas R, Gameiro P, Diss TC, Mills K, Morgan GJ, Carter GI, Milner BJ, Pearson D, Hummel M, Jung W, Ott M, Canioni D, Beldjord K, Bastard C, Delfau-Larue MH, van Dongen JJM, Molina TJ, Cabeçadas J (2007) Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4- CT98-3936. Leukemia 21:207–214. https://​doi.​org/​10.​1038/​sj.​leu.​2404479CrossRefPubMed
6.
go back to reference Langerak AW, Molina TJ, Lavender FL, Pearson D, Flohr T, Sambade C, Schuuring E, al Saati T, van Dongen JJM, van Krieken JHJM (2007) PCR-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. A study from the BIOMED-2 Concerted Action BMH4-CT98- 3936. Leukemia 21:222–229. https://doi.org/10.1038/sj.leu.2404482CrossRefPubMed Langerak AW, Molina TJ, Lavender FL, Pearson D, Flohr T, Sambade C, Schuuring E, al Saati T, van Dongen JJM, van Krieken JHJM (2007) PCR-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. A study from the BIOMED-2 Concerted Action BMH4-CT98- 3936. Leukemia 21:222–229. https://​doi.​org/​10.​1038/​sj.​leu.​2404482CrossRefPubMed
15.
go back to reference International Organization for Standardization (2012) ISO 15189:2012 Medical laboratories - particular requirements for quality and competence. ISO, Geneva International Organization for Standardization (2012) ISO 15189:2012 Medical laboratories - particular requirements for quality and competence. ISO, Geneva
25.
go back to reference van Krieken JH, Normanno N, Blackhall F, Boone E, Botti G, Carneiro F, Celik I, Ciardiello F, Cree IA, Deans ZC, Edsjö A, Groenen PJTA, Kamarainen O, Kreipe HH, Ligtenberg MJL, Marchetti A, Murray S, Opdam FJM, Patterson SD, Patton S, Pinto C, Rouleau E, Schuuring E, Sterck S, Taron M, Tejpar S, Timens W, Thunnissen E, van de Ven PM, Siebers AG, Dequeker E (2013) Guideline on the requirements of external quality assessment programs in molecular pathology. Virchows Arch 462(1):27–37. https://doi.org/10.1007/s00428-012-1354-4CrossRefPubMed van Krieken JH, Normanno N, Blackhall F, Boone E, Botti G, Carneiro F, Celik I, Ciardiello F, Cree IA, Deans ZC, Edsjö A, Groenen PJTA, Kamarainen O, Kreipe HH, Ligtenberg MJL, Marchetti A, Murray S, Opdam FJM, Patterson SD, Patton S, Pinto C, Rouleau E, Schuuring E, Sterck S, Taron M, Tejpar S, Timens W, Thunnissen E, van de Ven PM, Siebers AG, Dequeker E (2013) Guideline on the requirements of external quality assessment programs in molecular pathology. Virchows Arch 462(1):27–37. https://​doi.​org/​10.​1007/​s00428-012-1354-4CrossRefPubMed
30.
go back to reference International Organization for Standardization (2010) ISO 17043:2010 Conformity assessment - general requirements for proficiency testing. ISO, Geneva International Organization for Standardization (2010) ISO 17043:2010 Conformity assessment - general requirements for proficiency testing. ISO, Geneva
Metadata
Title
Evaluation of a worldwide EQA scheme for complex clonality analysis of clinical lymphoproliferative cases demonstrates a learning effect
Authors
Cleo Keppens
Elke Boone
Paula Gameiro
Véronique Tack
Elisabeth Moreau
Elizabeth Hodges
Paul Evans
Monika Brüggemann
Ian Carter
Dido Lenze
Maria Eugenia Sarasquete
Markus Möbs
Hongxiang Liu
Elisabeth M. C. Dequeker
Patricia J. T. A. Groenen
Publication date
01-08-2021
Publisher
Springer Berlin Heidelberg
Published in
Virchows Archiv / Issue 2/2021
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-021-03046-0

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