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Ependymoma gene expression profiles associated with histological subtype, proliferation, and patient survival

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Abstract

Ependymomas are primary tumors of the central nervous system that typically originate from the walls of the cerebral ventricles or from the spinal canal. The pathogenesis of these tumors is poorly understood, and prognostic assessment based on histologic features and clinical parameters is difficult. The aim of this study was to investigate the molecular heterogeneity of ependymomas. We used cDNA microarrays and RT-PCR to examine gene expression in 47 ependymomas. We present results for five comparisons: (1) tumors from children and adults with poor versus favorable outcome, (2) tumors from children with poor versus favorable outcome, (3) tumors with high versus low proliferation indices, (4) subependymomas versus myxopapillary ependymomas, and (5) spinal versus intracranial ependymomas. For patients with an overall survival >10 years after diagnosis, we identified 27 genes associated with favorable prognosis. In contrast, overexpression of BNIP3, MRC1, EPHB3, GLIS3, CDK4, COL4A2, EBP, NRCAM, and CCNA1 genes in tumors with high proliferation indices was associated with a poor outcome. Thirty genes, including ETV6, YWHAE, TOP2A, TLR2, IRAK1, TIA1, and UFD1L were found to be highly expressed in subependymomas but not myxopapillary ependymomas. Also, 30 genes were differentially expressed in spinal versus intracranial ependymomas. There was no relationship between expression profiles and tumor grade, patient age, and patient gender. Our results provide insight into specific molecular events underlying ependymoma tumorigenesis and may contribute to more accurate diagnosis and prediction of clinical outcome.

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Acknowledgments

This investigation was supported by a grant from the Sander Foundation (no. 99.070.2). We thank Hannelore Schraut and Margarete Göbel for excellent technical assistance and Miryame Hofmann for her assistance in performing the RT-PCR. We thank Dr. Vladimir V. Lukashov, and Dr. Andreas Rosenwald for critical review of the manuscript.

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Authors and Affiliations

  1. Department of Neuropathology, Institute of Pathology, University of Würzburg, Josef-Schneider-Str.2, 97080, Würzburg, Germany

    Inna Lukashova-v.Zangen, Camelia-Maria Monoranu & Wolfgang Roggendorf

  2. Laboratory of Microarray Application, IZKF, University of Würzburg, Würzburg, Germany

    Susanne Kneitz

  3. Children’s Hospital (Pediatric Oncology), University of Würzburg, Würzburg, Germany

    Stefan Rutkowski & Bernward Hinkes

  4. Clinic of Neurosurgery, University of Würzburg, Würzburg, Germany

    Giles Hamilton Vince

  5. Institute of Pathology, University of Würzburg, Würzburg, Germany

    Bei Huang

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  1. Inna Lukashova-v.Zangen
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  3. Camelia-Maria Monoranu
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Correspondence to Wolfgang Roggendorf.

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Lukashova-v.Zangen, I., Kneitz, S., Monoranu, CM. et al. Ependymoma gene expression profiles associated with histological subtype, proliferation, and patient survival. Acta Neuropathol 113, 325–337 (2007). https://doi.org/10.1007/s00401-006-0190-5

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