Analysis of EGFR gene amplification, protein over-expression and tyrosine kinase domain mutation in recurrent glioblastoma

Pathol Oncol Res. 2009 Jun;15(2):225-9. doi: 10.1007/s12253-008-9082-4. Epub 2008 Aug 28.


Gefitinib and erlotinib are both selective EGFR tyrosine kinase inhibitors (EGFR-TKIs) that have produced responses in a small subgroup of lung cancer patients. The strongest evidence for a role of EGFR in the biology of glioblastoma stems from clinical trials in which 15-20% of recurrent glioblastoma patients experienced significant tumour regression in response to these small-molecule EGFR kinase inhibitors. We examined the protein-kinase domain of the EGFR gene, EGFR protein expression and EGFR gene amplification in 20 cases of recurrent GBMs. EGFR protein over-expression was found in 65% of cases. EGFR protein over-expression was associated with EGFR gene amplification in 35% of cases, and with high polysomy in 15% of cases. No mutations were found in the TK domain of the EGFR gene. Our results confirm that mutations in the kinase domain are absent in recurrent GBM, and this might be a preponderant factor in the lack of major clinical responses of TKIs in GBM, recent studies have suggested that responsiveness to EGFR kinase inhibitors was strongly associated with coexpression of EGFRvIII and PTEN. Further prospective validation of EGFRvIII and PTEN as predictors of the clinical response to EGFR kinase inhibitors in recurrent GBM is strongly anticipated.

MeSH terms

  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism*
  • Gene Amplification*
  • Glioblastoma / genetics*
  • Glioblastoma / metabolism*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Mutation / genetics*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / metabolism
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases / genetics*


  • Protein Kinase Inhibitors
  • epidermal growth factor receptor VIII
  • EGFR protein, human
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human