title: Predominant expression of mutant EGFR (EGFRvIII) is rare in primary glioblastomas.
abstract: EGFR amplification is a frequent genetic alteration in primary (de novo) glioblastomas, and is often associated with structural alterations. Most common is variant III (EGFRvIII), which results from a non-random 801 bp in-frame deletion of exons 2 to 7 of the EGFR gene. We assessed amplification and overexpression of EGFRvIII and wild-type EGFR in 30 glioblastoma biopsies. Immunohistochemically, EGFR overexpression was observed in 20 (67%) of 30 glioblastomas. Eight (27%) cases also showed immunoreactivity to an EGFRvIII antibody. In 6 of these cases, the pattern of EGFR and EGFRvIII overexpression was compared in serial sections: In 4 cases, areas with immunoreactivity to EGFRvIII largely coincided with wild-type EGFR expression. In the other 2 cases, the areas immunoreactive to EGFRvIII were significantly less extensive than EGFR-positive areas. To assess whether EGFRvIII is predominantly amplified in tumors with concurrent wild-type EGFR amplification, we carried our real-time quantitative PCR using 2 sets of primers located in exon 2 and intron 15 of the EGFR gene. A > 5-fold ratio of relative copy numbers between intron 15 (present both in wild-type EGFR and EGFRvIII) and exon 2 (present only in wild-type EGFR, but missing in EGFRvIII) suggested predominant amplification of EGFRvIII in only 3 (10%) of 30 glioblastomas. The observation that intratumoral wild-type EGFR overexpression is often more extensive and that predominant amplification of EGFRvIII is a rare event would limit the effectiveness of therapeutic approaches based on selective targeting of EGFRvIII.
authors.affiliation: International Agency for Research on Cancer, 150 cours Albert Thomas, 60372 Lyon, France.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Biernat
authors.forename: Hervé
authors.initials: H
authors.lastname: Huang
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yokoo
authors.forename: Paul
authors.initials: P
authors.lastname: Kleihues
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ohgaki
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors