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Epidermal growth factor receptor overexpression is common and not correlated to gene copy number in ependymoma

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Abstract

Purpose

The aim of this study was to investigate the epidermal growth factor receptor (EGFR) status in ependymoma specimens, as there is a need for new prognostic and druggable targets in this disease.

Methods

Ependymomas (WHO grade II, n = 40; WHO grade III, n = 15) located spinal (n = 35), infratentorial (n = 14), and supratentorial (n = 6) of 53 patients with a median age of 40 (range, 2–79) years were analyzed for Ki-67, p53, and EGFR expression by immunohistochemistry using a tissue microarray and for EGFR gene copy number alterations/mutations. Results were correlated to clinical data.

Results

EGFR overexpression was found in 30/60 % of ependymomas depending on the antibody used and was more pronounced in WHO grade III. High EGFR gene copy number gains were found in 6 (11 %) ependymomas with half of them being amplifications. EGFR amplified ependymomas displayed an EGFR overexpression with both antibodies in two of three cases. A missense mutation in exon 20 of EGFR (S768I) was detected in one amplified case.

Conclusions

EGFR is frequently overexpressed in ependymomas. Other mechanisms than amplification of the EGFR gene appear to contribute to EGFR overexpression in most cases. EGFR mutations may be present in a small subset of ependymomas.

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Acknowledgments

We thank A. Blaszcyk-Wewer for help with EGFR sequencing, S. Eghtessadi for help with EGFR FISH, and A. Treszl (M.D., Ph.D.) for statistical advice. This work was supported by the University Cancer Center Hamburg and Euronanomed II “GlioEx.”

Author information

Authors and Affiliations

  1. Division of Pediatric Oncology, Hematology and Hemostaseology, Department of Woman’s and Children’s Health, University Hospital Leipzig, Leipzig, Germany

    Carsten Friedrich

  2. Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    André O. von Bueren

  3. Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University Medical Center Goettingen, Goettingen, Germany

    André O. von Bueren

  4. Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany

    Larissa Kolevatova, Christian Bernreuther, Diego Sepulveda-Falla & Markus Glatzel

  5. Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Tobias Grob & Ronald Simon

  6. Department of Neurological Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Leander van den Boom & Manfred Westphal

  7. Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University Hospital of Geneva, Geneva, Switzerland

    André O. von Bueren

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  1. Carsten Friedrich
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Correspondence to Markus Glatzel.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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The authors declare that they have no conflict of interest.

Additional information

Carsten Friedrich and André O. von Bueren contributed equally to this work.

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Friedrich, C., von Bueren, A.O., Kolevatova, L. et al. Epidermal growth factor receptor overexpression is common and not correlated to gene copy number in ependymoma. Childs Nerv Syst 32, 281–290 (2016). https://doi.org/10.1007/s00381-015-2981-2

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  • DOI: https://doi.org/10.1007/s00381-015-2981-2

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