Gupta A, Young R J, Shah A D, Schweitzer A D, Graber J J, Shi W, Zhang Z, Huse J, Omuro A M P
Department of Radiology, Weill Cornell Medical College and New York Presbyterian Hospital, New York, NY, USA.
Clin Neuroradiol. 2015 Jun;25(2):143-50. doi: 10.1007/s00062-014-0289-3. Epub 2014 Jan 29.
Molecular and genetic testing is becoming increasingly relevant in GBM. We sought to determine whether dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) perfusion imaging could predict EGFR-defined subtypes of GBM.
We retrospectively identified 106 consecutive glioblastoma (GBM) patients with known EGFR gene amplification, and a subset of 65 patients who also had known EGFRvIII gene mutation status. All patients underwent T2* DSC MRI perfusion. DSC perfusion maps and T2* signal intensity time curves were evaluated, and the following measures of tumor perfusion were recorded: (1) maximum relative cerebral blood volume (rCBV), (2) relative peak height (rPH), and (3) percent signal recovery (PSR). The imaging metrics were correlated to EGFR gene amplification and EGFRvIII mutation status using univariate analyses.
EGFR amplification was present in 44 (41.5 %) subjects and absent in 62 (58.5 %). Among the 65 subjects who had undergone EGFRvIII mutation transcript analysis, 18 subjects (27.7 %) tested positive for the EGFRvIII mutation, whereas 47 (72.3 %) did not. Higher median rCBV (3.31 versus 2.62, p = 0.01) and lower PSR (0.70 versus 0.78, p = 0.03) were associated with high levels of EGFR amplification. Higher median rPH (3.68 versus 2.76, p = 0.03) was associated with EGFRvIII mutation.
DSC MRI perfusion may have a role in identifying patients with EGFR gene amplification and EGFRvIII gene mutation status, potential targets for individualized treatment protocols. Our results raise the need for further investigation for imaging biomarkers of genetically unique GBM subtypes.
分子和基因检测在胶质母细胞瘤（GBM）中的应用越来越广泛。我们试图确定动态磁敏感对比（DSC）磁共振成像（MRI）灌注成像是否能够预测GBM中由表皮生长因子受体（EGFR）定义的亚型。
我们回顾性纳入了106例连续的已知EGFR基因扩增的胶质母细胞瘤（GBM）患者，以及其中65例同时已知EGFRvIII基因突变状态的患者子集。所有患者均接受了T2* DSC MRI灌注检查。对DSC灌注图和T2*信号强度时间曲线进行评估，并记录以下肿瘤灌注指标：（1）最大相对脑血容量（rCBV），（2）相对峰值高度（rPH），以及（3）信号恢复百分比（PSR）。采用单因素分析将影像学指标与EGFR基因扩增及EGFRvIII突变状态进行相关性分析。
44例（41.5%）受试者存在EGFR扩增，62例（58.5%）不存在EGFR扩增。在65例接受EGFRvIII突变转录分析的受试者中，18例（27.7%）EGFRvIII突变检测呈阳性，47例（72.3%）未检测到突变。较高的rCBV中位数（3.31对2.62，p = 0.01）和较低的PSR（0.70对0.78，p = 0.03）与高水平的EGFR扩增相关。较高的rPH中位数（3.68对2.76，p = 0.03）与EGFRvIII突变相关。
DSC MRI灌注成像可能有助于识别具有EGFR基因扩增和EGFRvIII基因突变状态的患者，这些是个体化治疗方案的潜在靶点。我们的结果提示，需要进一步研究具有基因独特性的GBM亚型的影像学生物标志物。
