Departments of Neurosurgery, Hospital of The University of Pennsylvania and The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Neuro Oncol. 2012 May;14(5):613-23. doi: 10.1093/neuonc/nos073. Epub 2012 Apr 4.
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.
表皮生长因子受体变异 III（EGFRvIII）突变在胶质母细胞瘤中的鉴定在优化治疗方面变得越来越重要。传统上，肿瘤 EGFRvIII 表达的测定依赖于基于组织的诊断。在这里，我们评估磁共振灌注加权成像（MR-PWI）在区分 EGFRvIII 表达的胶质母细胞瘤亚型中的准确性。我们通过逆转录聚合酶链反应（RT-PCR）分析了 132 例原发性人胶质母细胞瘤组织样本中的 EGFRvIII 和 EGFR 野生型突变，并通过定量 RT-PCR 分析了血管内皮生长因子（VEGF）的表达。同时，3 位独立观察者回顾性分析了这些肿瘤的术前 1.5T/SE 或 3.0T/GE MR 灌注图像，以确定每个肿瘤的最大相对肿瘤血容量（rTBV）。与缺乏 EGFRvIII 表达的肿瘤相比，EGFRvIII 表达的胶质母细胞瘤的 rTBV 明显更高。这种关联在 1.5T/SE（P=0.000）和 3.0T/GE（P=0.001）队列中均观察到。通过逻辑回归分析，将 2 个 MR 系统队列相结合，rTBV 是 EGFRvIII 突变的非常强的预测因子（比值比[rTBV]=2.70；P=0.000；McFadden's ρ(2)=0.23）。此外，通过接收者操作特征曲线分析，rTBV 以非常高的准确性（A(z)=0.81）区分 EGFRvIII。此外，我们发现 VEGF 的上调与 EGFRvIII 的表达（P=0.16）和 rTBV 的增加（F 比=2.71；P=0.102）相关，但没有达到统计学意义。这些趋势表明，VEGF 介导的血管生成可能是增加 EGFRvIII 表达的胶质母细胞瘤灌注的潜在介导因素，但可能还有其他几个促成因素。这项研究表明，使用 rTBV（一种源自磁共振灌注加权成像的参数）作为 EGFRvIII 突变的无创替代物具有潜力。
