title: Correlation of EGFR, IDH1 and PTEN status with the outcome of patients             with recurrent glioblastoma treated in a phase II clinical trial with the EGFR-blocking             monoclonal antibody cetuximab.
abstract: Mutation and gene amplification of the epithelial growth factor receptor             (EGFR) is one of the most common genetic alterations in glioblastoma (GB). EGFR             is, therefore, an attractive molecular target for the treatment of GB. EGFR-targeted             therapies however have been largely ineffective in clinical trials. In this study,             we investigated the correlation between the EGFR gene amplification status, expression             of the EGFR variant III (EGFRvIII) and EGFR variant IV (EGFRvIV) mutations, expression             of the phosphatase and tensin homologue gene on chromosome 10 (PTEN) and mutation             of the isocitrate dehydrogenase 1 (IDH1) gene and the survival of patients suffering             from recurrent glioblastoma who were treated with the EGFR-targeted monoclonal             antibody cetuximab in a prospective phase II clinical trial. EGFR amplification             was detected in 19 out of 35 GB (54%), EGFRvIII expression in 11 (31.4%) and EGFRvIV             expression in 7 (20%). The EGFRvIII and EGFRvIV mutations were exclusively found             in GB with EGFR amplification and were almost mutually exclusive with IDH1 mutation             (EGFRvIII mutation was found in 1 out of 11 GB with an IDH1 mutation). Patients             with an EGFR amplification lacking EGFRvIII expression had a significantly superior             progression free survival (PFS) and a numerical better overall survival (OS) following             treatment with cetuximab [median PFS 3.03 vs. 1.63 months (p=0.006); median OS             5.57 vs. 3.97 months (p=0.12)]. Within the subgroup of patients with EGFR amplification,             patients with EGFRvIII positive glioblastoma had a worse survival [median PFS             1.63 vs. 3.03 months (p=0.01); median OS 3.27 vs. 5.57 months (p=0.08)]. Our observations             indicate that the type of EGFR mutation may determine the outcome of GB patients             treated with cetuximab. Prospective investigation of both the EGFR amplification             and mutation status in clinical trials with EGFR-targeted therapies for GB is             indicated.
authors: Laboratory of Molecular Oncology and Department of Medical Oncology,                     University Hospital Brussels, Free University Brussels, 1090 Brussels,                     Belgium.
authors: Shasha
authors: S
authors: Lv
authors: Erik
authors: E
authors: Teugels
authors: Jan
authors: J
authors: Sadones
authors: Sylvia
authors: S
authors: De Brakeleer
authors: Johnny
authors: J
authors: Duerinck
authors: Stephanie
authors: S
authors: Du Four
authors: Alex
authors: A
authors: Michotte
authors: Jacques
authors: J
authors: De Grève
authors: Bart
authors: B
authors: Neyns
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality; D000068818:Cetuximab; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000068818:Cetuximab