Department of Radiology, Seoul National University College of Medicine, Seoul, Korea.
PLoS One. 2013 Aug 19;8(8):e71704. doi: 10.1371/journal.pone.0071704. eCollection 2013.
To evaluate the usefulness of dynamic susceptibility contrast (DSC) enhanced perfusion MR imaging in predicting major genetic alterations in glioblastomas.
Twenty-five patients (M:F = 13∶12, mean age: 52.1±15.2 years) with pathologically proven glioblastoma who underwent DSC MR imaging before surgery were included. On DSC MR imaging, the normalized relative tumor blood volume (nTBV) of the enhancing solid portion of each tumor was calculated by using dedicated software (Nordic TumorEX, NordicNeuroLab, Bergen, Norway) that enabled semi-automatic segmentation for each tumor. Five major glioblastoma genetic alterations (epidermal growth factor receptor (EGFR), phosphatase and tensin homologue (PTEN), Ki-67, O6-methylguanine-DNA methyltransferase (MGMT) and p53) were confirmed by immunohistochemistry and analyzed for correlation with the nTBV of each tumor. Statistical analysis was performed using the unpaired Student t test, ROC (receiver operating characteristic) curve analysis and Pearson correlation analysis.
The nTBVs of the MGMT methylation-negative group (mean 9.5±7.5) were significantly higher than those of the MGMT methylation-positive group (mean 5.4±1.8) (p = .046). In the analysis of EGFR expression-positive group, the nTBVs of the subgroup with loss of PTEN gene expression (mean: 10.3±8.1) were also significantly higher than those of the subgroup without loss of PTEN gene expression (mean: 5.6±2.3) (p = .046). Ki-67 labeling index indicated significant positive correlation with the nTBV of the tumor (p = .01).
We found that glioblastomas with aggressive genetic alterations tended to have a high nTBV in the present study. Thus, we believe that DSC-enhanced perfusion MR imaging could be helpful in predicting genetic alterations that are crucial in predicting the prognosis of and selecting tailored treatment for glioblastoma patients.
评估动态磁敏感对比(DSC)增强灌注磁共振成像在预测胶质母细胞瘤主要遗传改变中的作用。
本研究共纳入 25 例经病理证实的胶质母细胞瘤患者(男 13 例,女 12 例;平均年龄 52.1±15.2 岁),这些患者均在术前接受了 DSC 磁共振成像检查。在 DSC 磁共振成像上,使用专用软件(Nordic TumorEX,NordicNeuroLab,卑尔根,挪威)计算每个肿瘤强化实体部分的标准化相对肿瘤血容量(nTBV),该软件能够对每个肿瘤进行半自动分割。通过免疫组织化学方法检测 5 种主要的胶质母细胞瘤遗传改变(表皮生长因子受体(EGFR)、磷酸酶和张力蛋白同源物(PTEN)、Ki-67、O6-甲基鸟嘌呤-DNA 甲基转移酶(MGMT)和 p53),并分析其与每个肿瘤 nTBV 的相关性。采用配对学生 t 检验、ROC 曲线分析和 Pearson 相关分析进行统计学分析。
MGMT 甲基化阴性组(nTBV 平均值为 9.5±7.5)的 nTBV 明显高于 MGMT 甲基化阳性组(nTBV 平均值为 5.4±1.8)(p = .046)。在 EGFR 表达阳性组中,PTEN 基因表达缺失亚组的 nTBV(nTBV 平均值为 10.3±8.1)明显高于 PTEN 基因表达未缺失亚组(nTBV 平均值为 5.6±2.3)(p = .046)。Ki-67 标记指数与肿瘤 nTBV 呈显著正相关(p = .01)。
本研究发现,侵袭性遗传改变的胶质母细胞瘤往往具有较高的 nTBV。因此,我们认为 DSC 增强灌注磁共振成像有助于预测遗传改变,这对于预测胶质母细胞瘤患者的预后和选择个体化治疗方案具有重要意义。