title: Assessment and prognostic significance of the epidermal growth factor receptor vIII mutation in glioblastoma patients treated with concurrent and adjuvant temozolomide radiochemotherapy.
abstract: The epidermal growth factor receptor vIII mutant (EGFRvIII) is found in ~50% of all EGFR-amplified glioblastomas and constitutes a tumor-specific therapeutic target. To assess molecular testing approaches and the prognostic role of EGFRvIII in patients treated according to current standards of care, we compared different EGFRvIII detection methods and correlated EGFRvIII status with outcome in a prospective patient cohort of the German Glioma Network. In total, 184 newly diagnosed glioblastoma patients were investigated for EGFR amplification and for expression of EGFR and EGFRvIII by immunohistochemistry. Further, the EGFRvIII status was additionally studied by multiplex ligation-dependent probe amplification (MLPA) analysis and reverse transcription-PCR (RT-PCR). Immunohistochemistry demonstrated EGFRvIII in 34 of 184 patients (18%). RT-PCR or MLPA analysis detected four additional EGFRvIII-positive patients. Overall, RT-PCR and immunohistochemistry were more sensitive for EGFRvIII detection than MLPA. EGFRvIII status was not associated with progression-free and overall survival. EGFRvIII also had no prognostic significance in the subgroup of patients who were free from progression after concomitant radiochemotherapy and thus would be eligible for the ongoing ACT IV EGFRvIII vaccination trial. Age, extent of resection and O⁶-methylguanine DNA methyltransferase (MGMT) promoter methylation status appeared to be less prognostic in EGFRvIII-positive patients. Thus, EGFRvIII positivity is not a major negative prognostic factor in glioblastoma patients treated according to current standards of care. Data from phase II EGFRvIII-targeted vaccination trials compare favorably with the present contemporary results, supporting the further exploration of EGVRvIII vaccination in newly diagnosed glioblastoma.
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kaulich
authors.forename: Bettina
authors.initials: B
authors.lastname: Hentschel
authors.forename: Joerg
authors.initials: J
authors.lastname: Felsberg
authors.forename: Dorothee
authors.initials: D
authors.lastname: Gramatzki
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Matthias
authors.initials: M
authors.lastname: Simon
authors.forename: Manfred
authors.initials: M
authors.lastname: Westphal
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schackert
authors.forename: Joerg C
authors.initials: JC
authors.lastname: Tonn
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Thomas
authors.initials: T
authors.lastname: Davis
authors.forename: William Andrew
authors.initials: WA
authors.lastname: Weiss
authors.forename: Markus
authors.initials: M
authors.lastname: Loeffler
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D015153:Blotting, Western; D059248:Chemoradiotherapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000601:surgery / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; C410723:epidermal growth factor receptor VIII; D003606:Dacarbazine; D066246:ErbB Receptors; D000077204:Temozolomide