Journal of Neuro-Oncology

, Volume 108, Issue 3, pp 395–402

Expression of epidermal growth factor variant III (EGFRvIII) in pediatric diffuse intrinsic pontine gliomas

  • Gordon Li
  • Siddhartha S. Mitra
  • Michelle Monje
  • Kristy N. Henrich
  • C. Dana Bangs
  • Ryan T. Nitta
  • Albert J. Wong
Laboratory Investigation

Abstract

Despite numerous clinical trials over the past 2 decades, the overall survival for children diagnosed with diffuse intrinsic pontine glioma (DIPG) remains 9–10 months. Radiation therapy is the only treatment with proven effect and novel therapies are needed. Epidermal growth factor receptor variant III (EGFRvIII) is the most common variant of the epidermal growth factor receptor and is expressed in many tumor types but is rarely found in normal tissue. A peptide vaccine targeting EGFRvIII is currently undergoing investigation in phase 3 clinical trials for the treatment of newly diagnosed glioblastoma (GBM), the tumor in which this variant receptor was first discovered. In this study, we evaluated EGFRvIII expression in pediatric DIPG samples using immunohistochemistry with a double affinity purified antibody raised against the EGFRvIII peptide. Staining of pediatric DIPG histological samples revealed expression in 4 of 9 cases and the pattern of staining was consistent with what has been seen in EGFRvIII transfected cells as well as GBMs from adult trials. In addition, analysis of tumor samples collected immediately post mortem and of DIPG cells in culture by RT-PCR, western blot analysis, and flow cytometry confirmed EGFRvIII expression. We were therefore able to detect EGFRvIII expression in 6 of 11 DIPG cases. These data suggest that EGFRvIII warrants investigation as a target for these deadly pediatric tumors.

Keywords

Diffuse intrinsic brain stem glioma (DIPG) Epidermal growth factor variant III (EGFRvIII) Immunotherapy Cancer vaccine 

Supplementary material

11060_2012_842_MOESM1_ESM.docx (43 kb)
Supplemental Figure 1: Maintenance of EGFRvIII in DIPG-1 tumorsphere line was observed at passage 21. Co-stain with anti-nestin antibody shows >80% of the cells to co-express EGFRvIII and nestin (DOCX 43.3 kb)

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Gordon Li
    • 1
    • 5
  • Siddhartha S. Mitra
    • 1
    • 4
  • Michelle Monje
    • 2
  • Kristy N. Henrich
    • 1
  • C. Dana Bangs
    • 3
  • Ryan T. Nitta
    • 1
  • Albert J. Wong
    • 1
  1. 1.Department of NeurosurgeryStanford University Medical CenterStanfordUSA
  2. 2.Department of NeurologyStanford University Medical CenterStanfordUSA
  3. 3.Department of Pathology, Cytogenetics LaboratoryStanford University Medical CenterStanfordUSA
  4. 4.Institute of Stem Cell Biology and Regenerative Medicine, Ludwig Center for Cancer Stem Research and MedicineStanford University Medical CenterStanfordUSA
  5. 5.Department of NeurosurgeryStanford University School of MedicineStanfordUSA

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