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Nestin Expression Identifies Ependymoma Patients with Poor Outcome

Authors

  • Till Milde,

    Corresponding author
    1. Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Heidelberg, Germany
    2. Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany
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  • Thomas Hielscher,

    1. Division of Biostatistics (C060), German Cancer Research Center (DKFZ), Heidelberg, Germany
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  • Hendrik Witt,

    1. Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany
    2. Division of Pediatric Neurooncology (B062), German Cancer Research Center (DKFZ), Heidelberg, Germany
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  • Marcel Kool,

    1. Division of Pediatric Neurooncology (B062), German Cancer Research Center (DKFZ), Heidelberg, Germany
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  • Stephen C. Mack,

    1. Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
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  • Hedwig E. Deubzer,

    1. Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Heidelberg, Germany
    2. Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany
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  • Ina Oehme,

    1. Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Heidelberg, Germany
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  • Marco Lodrini,

    1. Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Heidelberg, Germany
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  • Axel Benner,

    1. Division of Biostatistics (C060), German Cancer Research Center (DKFZ), Heidelberg, Germany
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  • Michael D. Taylor,

    1. Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada
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  • Andreas von Deimling,

    1. Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany
    2. Clinical Cooperation Unit Neuropathology (G380), German Cancer Research Center (DKFZ), Heidelberg, Germany
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  • Andreas E. Kulozik,

    1. Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany
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  • Stefan M. Pfister,

    1. Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Heidelberg, Germany
    2. Division of Pediatric Neurooncology (B062), German Cancer Research Center (DKFZ), Heidelberg, Germany
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  • Olaf Witt,

    1. Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center (DKFZ), Heidelberg, Germany
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    • These authors contributed equally to this work.

  • Andrey Korshunov

    1. Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany
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    • These authors contributed equally to this work.


  • Conflict of interest: The authors declare no conflict of interest.

Till Milde, MD, Clinical Cooperation Unit Pediatric Oncology (G340), German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany (E-mail: t.milde@dkfz.de). Department of Pediatric Oncology, Hematology and Immunology, University Hospital Heidelberg, Im Neuenheimer Feld 430, 69120 Heidelberg, Germany

Abstract

Ependymomas are primary brain tumors found throughout the central nervous system (CNS) in children and adults. Currently, many treatment protocols stratify grade I and II ependymomas as low-risk tumors, whereas grade III anaplastic ependymomas are considered high-risk tumors. The prognostic significance of World Health Organization (WHO) grade II or III, however, remains debated, and it is furthermore increasingly recognized that the pathologic differentiation between grades II and III is arbitrary in daily practice, thus resulting in imprecise risk stratification. Therefore, prognostic markers enabling more precise stratification to guide treatment decisions are urgently needed. An analysis of n = 379 tumor samples revealed that protein expression of nestin, a marker for neural stem and progenitor cells established as a routine staining in most neuropathology centers, is associated with poor outcome in intracranial ependymomas. Most importantly, nestin-positive grade II ependymomas have the same prognosis as grade III ependymomas. Multivariable analysis demonstrates that nestin positivity is an independent marker for poor progression-free survival (PFS) and overall survival (OS). Gene expression analysis for transcriptionally co-regulated genes revealed a strong association of developmental and epigenetic processes with nestin. In summary, our data implicate nestin as a useful novel marker for intracranial ependymoma risk stratification easily implementable in routine diagnostics.

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