title: Use of magnetic perfusion-weighted imaging to determine epidermal growth factor receptor variant III expression in glioblastoma.
abstract: Identification of the epidermal growth factor receptor variant III (EGFRvIII) mutation in glioblastoma has become increasingly relevant in the optimization of therapy. Traditionally, determination of tumor EGFRvIII-expression has relied on tissue-based diagnostics. Here, we assess the accuracy of magnetic resonance perfusion-weighted imaging (MR-PWI) in discriminating the EGFRvIII-expressing glioblastoma subtype. We analyzed RNA from 132 primary human glioblastoma tissue samples by reverse-transcription polymerase chain reaction (RT-PCR) for the EGFRvIII and EGFR wild-type mutations and by quantitative RT-PCR for expression of vascular endothelial growth factor (VEGF). Concurrently, 3 independent observers reviewed preoperative 1.5-Tesla (T)/SE or 3.0-Tesla (T)/GE MR perfusion images to determine the maximum relative tumor blood volume (rTBV) of each of these tumors. EGFRvIII-expressing glioblastomas showed significantly higher rTBV, compared with those tumors lacking EGFRvIII expression. This association was observed in both the 1.5T/SE (P = .000) and 3.0T/GE (P = .001) cohorts. By logistic regression analysis, combining the 2 MR system cohorts, rTBV was a very strong predictor of EGFRvIII mutation (odds ratio [rTBV] = 2.70; P = .000; McFadden's ρ(2) = 0.23). Furthermore, by receiver-operating characteristic curve analysis, rTBV discriminated EGFRvIII with very high accuracy (A(z) = 0.81). In addition, we found that VEGF upregulation was associated, although without reaching statistical significance, with EGFRvIII expression (P = .16) and with increased rTBV (F-ratio = 2.71; P = .102). These trends suggest that VEGF-mediated angiogenesis may be a potential mediator of angiogenesis to increase perfusion in EGFRvIII-expressing glioblastomas, but there are likely several other contributing factors. This study demonstrates the potential to use rTBV, a MR-PWI-derived parameter, as a noninvasive surrogate of the EGFRvIII mutation.
authors.affiliation: Departments of Neurosurgery, Hospital of The University of Pennsylvania and The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Elana S
authors.initials: ES
authors.lastname: Tykocinski
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Grant
authors.forename: Gurpreet S
authors.initials: GS
authors.lastname: Kapoor
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Krejza
authors.forename: Leif-Erik
authors.initials: LE
authors.lastname: Bohman
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Gocke
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Chawla
authors.forename: Casey H
authors.initials: CH
authors.lastname: Halpern
authors.forename: Joanna
authors.initials: J
authors.lastname: Lopinto
authors.forename: Elias R
authors.initials: ER
authors.lastname: Melhem
authors.forename: Donald M
authors.initials: DM
authors.lastname: O'Rourke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009389:Neovascularization, Pathologic; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors