Use of magnetic perfusion-weighted imaging to determine epidermal growth factor receptor variant III expression in glioblastoma
Open Access
- 4 April 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Neuro-Oncology
- Vol. 14 (5), 613-623
- https://doi.org/10.1093/neuonc/nos073
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 ρ2 = 0.23). Furthermore, by receiver-operating characteristic curve analysis, rTBV discriminated EGFRvIII with very high accuracy (Az = 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.Keywords
This publication has 46 references indexed in Scilit:
- Tumor-specific immunotherapy targeting the EGFRvIII mutation in patients with malignant gliomaSeminars in Immunology, 2008
- Vascular Endothelial Growth Factor: Basic Science and Clinical ProgressEndocrine Reviews, 2004
- Glioma Grading: Sensitivity, Specificity, and Predictive Values of Perfusion MR Imaging and Proton MR Spectroscopic Imaging Compared with Conventional MR Imaging2003
- Prognostic value of epidermal growth factor receptor in patients with glioblastoma multiforme.2003
- Preoperative Assessment of Intracranial Tumors with Perfusion MR and a Volumetric Interpolated Examination: A Comparative Study with DSA2002
- Relative Cerebral Blood Volume Measurements in Intracranial Mass Lesions: Interobserver and Intraobserver Reproducibility StudyRadiology, 2002
- Histological yield, complications, and technological considerations in 114 consecutive frameless stereotactic biopsy procedures aided by open intraoperative magnetic resonance imagingJournal of Neurosurgery, 2002
- Intracranial Mass Lesions: Dynamic Contrast-enhanced Susceptibility-weighted Echo-planar Perfusion MR ImagingRadiology, 2002
- Quantification of VEGF mRNA Expression in Non-Small Cell Lung Cancer Using a Real-Time Quantitative Reverse Transcription-PCR Assay and a Comparison with Quantitative Competitive Reverse Transcription-PCRLaboratory Investigation, 2000
- Expression of Activated Epidermal Growth Factor Receptors, Ras-Guanosine Triphosphate, and Mitogen-activated Protein Kinase in Human Glioblastoma Multiforme SpecimensNeurosurgery, 1999