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Interlaboratory comparison of IDH mutation detection

  • Laboratory Investigation
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Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Isocitrate dehydrogenase (IDH) mutational testing is becoming increasingly important. For this, robust and reliable assays are needed. We tested the variation of results between six laboratories of testing for IDH mutations. Each laboratory received five unstained slides from 31 formalin-fixed paraffin-embedded (FFPE) glioma samples, and followed its own standard IDH diagnostic routine. All laboratories used immunohistochemistry (IHC) with an antibody against the most frequent IDH1 mutation (R132H) as a first step. Three laboratories then sequenced only IHC negative cases while the others sequenced all cases. Based on the overall analysis, 13 samples from 11 tumors had an R132H mutation and one tumor showed an R132G mutation. Results of IHC for IDH1 R132H mutations in all six laboratories were completely in agreement, and identified all R132H mutations. Upon sequencing the results of two laboratories deviated from those of the others. After a review of the entire diagnostic process, on repeat (blinded) testing one laboratory was completely in agreement with the overall result. A change in technique did only partially improve the results in the other laboratory. IHC for the IDH1 R132H mutation is very reliable and consistent across laboratories. IDH sequencing procedures yielded inconsistent results in 2 out of 6 laboratories. Quality assurance is pivotal before IDH testing is made part of clinical management of patients.

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Acknowledgments

The technical assistence of Marcel M. van der Weiden, Edward Post (ErasmusMC), Brooke E Mc Cann, Jesse S Voss (Mayo Clinics), Dr. Johannes A. Hainfellner (Institute of Neurology, Medical University of Vienna) is gratefully acknowledged. Dr Caterina Giannini was in part supported by Grant Number P50CA108961 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

Disclosure

Under a licensing agreement between DIANOVA GmbH, Hamburg, Germany, and the German Cancer Research Center, Andreas von Deimling and Christian Hartmann are entitled to a share of royalties received by the German Cancer Research Center on the sales of H09 antibody. The terms of this arrangement are being managed by the German Cancer Research Center in accordance with its conflict of interest policies.

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Authors and Affiliations

  1. Department of Neurology/Neuro-Oncology, Erasmus MC – Cancer Institute, Groene Hilledijk 301, 3075EA, Rotterdam, the Netherlands

    Martin J. van den Bent

  2. Department of Neuropathology, Institute of Pathology, Hannover Medical School, D-30625, Hannover, Germany

    C. Hartmann

  3. Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-Universität, Heidelberg, Germany

    C. Hartmann & Andreas von Deimling

  4. Clinical Cooperation Unit Neuropathology, German Cancer Research Center, Heidelberg, Germany

    C. Hartmann & Andreas von Deimling

  5. Department of Medicine I and Comprehensive Cancer Center CNS Uni, Medical University of Vienna, Vienna, Austria

    Matthias Preusser

  6. Institute of Neurology, Medical University of Vienna, Vienna, Austria

    Thomas Ströbel

  7. Department of Pathology Erasmus MC, Rotterdam, the Netherlands

    Hendrikus J. Dubbink & Johan M. Kros

  8. Centre de Recherche de l’Institut du Cerveau et de la Moelle épinière (CRICM) UMR-S975, Université Pierre et Marie Curie-Paris 6, et Service de Neurologie Mazarin GH Pitié-Salpêtrière, Paris, France

    Blandine Boisselier & Marc Sanson

  9. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Kevin C. Halling & Caterina Giannini

  10. Department of Pathology, MD Anderson Cancer Center, Houston, TX, USA

    Kristin L. Diefes & Kenneth Aldape

Authors
  1. Martin J. van den Bent
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  2. C. Hartmann
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  3. Matthias Preusser
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  4. Thomas Ströbel
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  5. Hendrikus J. Dubbink
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  6. Johan M. Kros
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  7. Andreas von Deimling
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  8. Blandine Boisselier
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  9. Marc Sanson
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  10. Kevin C. Halling
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  11. Kristin L. Diefes
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  12. Kenneth Aldape
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  13. Caterina Giannini
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Corresponding author

Correspondence to Martin J. van den Bent.

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van den Bent, M.J., Hartmann, C., Preusser, M. et al. Interlaboratory comparison of IDH mutation detection. J Neurooncol 112, 173–178 (2013). https://doi.org/10.1007/s11060-013-1056-z

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  • DOI: https://doi.org/10.1007/s11060-013-1056-z

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