title: Expression of epidermal growth factor variant III (EGFRvIII) in pediatric diffuse intrinsic pontine gliomas.
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.
authors.affiliation: Department of Neurosurgery, Stanford University Medical Center, Stanford, CA 94305, USA. gordonli@stanford.edu
authors.forename: Gordon
authors.initials: G
authors.lastname: Li
authors.forename: Siddhartha S
authors.initials: SS
authors.lastname: Mitra
authors.forename: Michelle
authors.initials: M
authors.lastname: Monje
authors.forename: Kristy N
authors.initials: KN
authors.lastname: Henrich
authors.forename: C Dana
authors.initials: CD
authors.lastname: Bangs
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Nitta
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Wong
mesh_terms: D000328:Adult; D015153:Blotting, Western; D020295:Brain Stem Neoplasms / Q000235:genetics* / Q000378:metabolism; D002675:Child, Preschool; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D010446:Peptide Fragments / Q000276:immunology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D010446:Peptide Fragments; D012333:RNA, Messenger; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors