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Clinical significance of EGFR amplification and the aberrant EGFRvIII transcript in conventionally treated astrocytic gliomas

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Abstract

The aim of this study was to evaluate the clinical value of assessing epidermal growth factor receptor (EGFR) amplification and the common 5′ rearrangement of EGFR resulting in the EGFRvIII transcript in astrocytic gliomas. Data from 221 tumours were correlated with patient survival. The majority of previous studies evaluated amplification alone and provided contradictory results. Amplification was analysed by a densitometry of Southern blot analysis or quantitative polymerase chain reaction (PCR). EGFR transcripts were examined by reverse transcription PCR and subsequent sequencing. A ribonuclease (RNase) protection assay was carried out on a subgroup to confirm PCR results. Amplification of EGFR was found in 41% (65/160) of glioblastomas (GBs) and 10% (4/41) of anaplastic astrocytomas (AAs). The EGFRvIII rearrangement was identified in 54% (35/65) of GBs and 75% (3/4) of AAs with amplification, as well as in 8% (8/95) of GBs and 5% (2/37) of AAs without amplification (confirmed by RNase protection assay). There were no abnormalities of the EFGR or its transcript in grade II astrocytoma (AII). We found no significant association between EGFR amplification or rearrangement, and age or survival in the 160 GB patients. We noted a tendency towards decreased survival with any EGFR abnormality in the 41 patients with AAs. This was most marked in the five cases with the EGFRvIII transcript (p=0.069), but these were significantly older than those without (p=0.023). No abnormalities of EGFR were identified in AII patients. We conclude that neither EGFR amplification nor the presence of the EGFRvIII transcript predicts patient outcome in conventionally treated GBs. However, in AAs, although uncommon, EGFR aberrations appear to be associated with shorter survival.

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Acknowledgements

We thank the Departments of Neurosurgery and Pathology at the Karolinska University Hospital, Sahlgrenska University Hospital, and many other hospitals in Sweden that helped us obtain follow-up data.

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Authors and Affiliations

  1. Division of Molecular Histopathology, Department of Pathology, Addenbrooke’s Hospital, University of Cambridge, P.O.Box 231, Cambridge, CB2 2QQ, UK

    Lu Liu, Koichi Ichimura & V. Peter Collins

  2. Department of Oncology–Pathology, Karolinska University Hospital, 171 76, Stockholm, Sweden

    L. Magnus Bäcklund, Bo R. Nilsson, Dan Grandér & Helena M. Goike

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  1. Lu Liu
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  2. L. Magnus Bäcklund
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  3. Bo R. Nilsson
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  4. Dan Grandér
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  5. Koichi Ichimura
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  6. Helena M. Goike
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  7. V. Peter Collins
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Correspondence to V. Peter Collins.

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This work was supported by grants from The Cambridge Fund for the Prevention of Disease, Cancer Research UK, The Ludwig Institute for Cancer Research, Jacqueline Serousse Memorial Foundation for Cancer Research and the Swedish Children’s Cancer Foundation

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Liu, L., Bäcklund, L.M., Nilsson, B.R. et al. Clinical significance of EGFR amplification and the aberrant EGFRvIII transcript in conventionally treated astrocytic gliomas. J Mol Med 83, 917–926 (2005). https://doi.org/10.1007/s00109-005-0700-2

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  • DOI: https://doi.org/10.1007/s00109-005-0700-2

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