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.

Fig. 1.

EGFRvIII expression correlates with higher maximum rTBV. Imaging from selected EGFRvIII (−) patients (A and C) and EGFRvIII (+) patients (B and D), with matched T1-post gadolinium (left), color 1.5-Tesla/SE MR perfusion (A and B, middle) or 3.0-Tesla/GE MR perfusion (C and D, middle), and 50% overlay (right). Black hatch marks (A–C and D, right) indicate representative voxels placed in regions of apparent maximum rTBV.

Fig. 2.

rTBV discriminates EGFRvIII expression with high accuracy, irrespective of MR-system type. ROC constructed based on rTBV values measured by 3 individual observers (green, violet, and orange lines) and based on rTBV averaged from the independent observers (red lines), using a (A) 1.5-Tesla/SE MR-system (n = 35) or (B) 3.0-Tesla/GE MR-system (n = 97). The interobserver variability in measurements, as demonstrated graphically and based on A_z values, varies from 0.893 to 0.985 using the 1.5-Tesla/SE MR-system (A) and from 0.716 to 0.753 using the 3.0-Tesla/GE MR-system (B).