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IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO

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Abstract

The WHO 2007 classification of tumors of the CNS distinguishes between diffuse astrocytoma WHO grade II (A IIWHO2007) and anaplastic astrocytoma WHO grade III (AA III WHO2007). Patients with A II WHO2007 are significantly younger and survive significantly longer than those with AA III WHO2007. So far, classification and grading relies on morphological grounds only and does not yet take into account IDH status, a molecular marker of prognostic relevance. We here demonstrate that WHO 2007 grading performs poorly in predicting prognosis when applied to astrocytoma carrying IDH mutations. Three independent series including a total of 1360 adult diffuse astrocytic gliomas with IDH mutation containing 683 A II IDHmut, 562 AA III IDHmut and 115 GBM IDHmut have been examined for age distribution and survival. In all three series patients with A II IDHmut and AA III IDHmut were of identical age at presentation of disease (36–37 years) and the difference in survival between grades was much less (10.9 years for A II IDHmut, 9.3 years for AA III IDHmut) than that reported for A II WHO2007 versus AA III WHO2007. Our analyses imply that the differences in age and survival between A II WHO2007 and AA III WHO2007 predominantly depend on the fraction of IDH-non-mutant astrocytomas in the cohort. This data poses a substantial challenge for the current practice of astrocytoma grading and risk stratification and is likely to have far-reaching consequences on the management of patients with IDH-mutant astrocytoma.

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Acknowledgments

AO was supported by the National Institutes of Health/National Cancer Institute (Training Grant No. 5T32CA163185). FS is a fellow of the Medical Faculty Heidelberg Physician-Scientist Program. PW and JCR were supported by grants of the Dutch Cancer Society (Grant No. VU 2009-4470) and Foundation ‘STOPHersentumoren.nl’. AvD was supported by the Bundesministerium fuer Bildung und Forschung (BMBF) program “SYS-GLIO”.

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    Authors and Affiliations

    1. Department of Neuropathology, Institute of Pathology, University of Heidelberg, INF 224, 69120, Heidelberg, Germany

      David E. Reuss, Daniel Schrimpf, David Capper, Annekathrin Kratz, Felix Sahm, Christian Koelsche, Andrey Korshunov & Andreas von Deimling

    2. CCU Neuropathology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), INF 224, 69120, Heidelberg, Germany

      David E. Reuss, Daniel Schrimpf, David Capper, Annekathrin Kratz, Felix Sahm, Christian Koelsche, Andrey Korshunov & Andreas von Deimling

    3. MacFeeters-Hamilton Brain Tumour Center, Princess Margaret Cancer Center, College Street 101, Toronto, ON, M5G 1L7, Canada

      Yasin Mamatjan & Kenneth Aldape

    4. Division of Molecular Genetics, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), INF 280, 69120, Heidelberg, Germany

      Volker Hovestadt

    5. Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX, 77030, USA

      Adriana Olar

    6. Department for Neuropathology, Institute of Pathology, Medizinische Hochschule Hannover, Carl Neuberg Str. 1, 30625, Hannover, Germany

      Christian Hartmann

    7. Department of Neurology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands

      Jaap C. Reijneveld

    8. Department of Pathology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands

      Pieter Wesseling

    9. Department of Pathology, Radboudt University Medical Center, PO Box 9101, Nijmegen, 6500 HB, The Netherlands

      Pieter Wesseling

    10. Department of Neurosurgery, University of Heidelberg, INF 400, 69120, Heidelberg, Germany

      Andreas Unterberg & Christel Herold-Mende

    11. CCU Neuroimmunology and Brain Tumor Immunology, German Cancer research Center, INF 400, 69120, Heidelberg, Germany

      Michael Platten

    12. Department of Neurooncology at the National Center for Tumor Diseases, University of Heidelberg, INF 400, 69120, Heidelberg, Germany

      Michael Platten & Wolfgang Wick

    13. CCU Neurooncology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany

      Wolfgang Wick

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    1. David E. Reuss
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    2. Yasin Mamatjan
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    Corresponding author

    Correspondence to Andreas von Deimling.

    Additional information

    K. Aldape and A. von Deimling contributed equally to the project.

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    Reuss, D.E., Mamatjan, Y., Schrimpf, D. et al. IDH mutant diffuse and anaplastic astrocytomas have similar age at presentation and little difference in survival: a grading problem for WHO. Acta Neuropathol 129, 867–873 (2015). https://doi.org/10.1007/s00401-015-1438-8

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    • DOI: https://doi.org/10.1007/s00401-015-1438-8

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