Department of Neurosurgery, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Cancer. 2010 Mar 15;116(6):1545-52. doi: 10.1002/cncr.24903.
Because of intratumoral heterogeneity, diffusely infiltrating gliomas that lack significant contrast enhancement on magnetic resonance imaging are prone to tissue sampling error. Subsequent histologic undergrading may delay adjuvant treatments. 5-Aminolevulinic acid (5-ALA) leads to accumulation of fluorescent porphyrins in malignant glioma tissue, and is currently used for resection of malignant gliomas. The aim of this study was to clarify whether 5-ALA might serve as marker for visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement for precise intraoperative tissue sampling.
5-ALA was administered in 17 patients with diffusely infiltrating gliomas with nonsignificant contrast enhancement. During glioma resection, positive fluorescence was noted by a modified neurosurgical microscope. Intraoperative topographic correlation of focal 5-ALA fluorescence with maximum (11)C-methionine positron emission tomography uptake (PET(max)) was performed. Multiple tissue samples were taken from areas of positive and/or negative 5-ALA fluorescence. Histopathological diagnosis was established according to World Health Organization (WHO) 2007 criteria. Cell proliferation was assessed for multiregional samples by MIB-1 labeling index (LI).
Focal 5-ALA fluorescence was observed in 8 of 9 patients with WHO grade III diffusely infiltrating gliomas. All 8 of 8 WHO grade II diffusely infiltrating gliomas were 5-ALA negative. Focal 5-ALA fluorescence correlated topographically with PET(max) in all patients. MIB-1 LI was significantly higher in 5-ALA-positive than in nonfluorescent areas within a given tumor.
The data indicate that 5-ALA is a promising marker for intraoperative visualization of anaplastic foci in diffusely infiltrating gliomas with nonsignificant contrast enhancement. Unaffected by intraoperative brain shift, 5-ALA may increase the precision of tissue sampling during tumor resection for histopathological grading, and therefore optimize allocation of patients to adjuvant treatments.
由于肿瘤内异质性，磁共振成像上缺乏明显对比增强的弥漫浸润性神经胶质瘤容易发生组织取样误差。随后的组织学降级可能会延迟辅助治疗。5-氨基酮戊酸（5-ALA）可导致恶性胶质瘤组织中荧光卟啉的积累，目前用于恶性胶质瘤的切除。本研究旨在阐明 5-ALA 是否可作为在磁共振成像上无明显增强的弥漫浸润性神经胶质瘤中可视化间变灶的标志物，以实现精确的术中组织取样。
17 例磁共振成像上无明显增强的弥漫浸润性神经胶质瘤患者接受 5-ALA 治疗。在进行胶质瘤切除时，使用改良的神经外科显微镜观察到阳性荧光。进行焦点 5-ALA 荧光与最大（11）C-蛋氨酸正电子发射断层扫描摄取（PET（max））的术中拓扑相关性。从阳性和/或阴性 5-ALA 荧光区域采集多个组织样本。根据世界卫生组织（WHO）2007 标准建立组织病理学诊断。通过 MIB-1 标记指数（LI）评估多区域样本中的细胞增殖。
9 例 WHO 级 III 弥漫浸润性神经胶质瘤中有 8 例观察到焦点 5-ALA 荧光。所有 8 例 WHO 级 II 弥漫浸润性神经胶质瘤均为 5-ALA 阴性。所有患者焦点 5-ALA 荧光与 PET（max）在拓扑上均相关。在给定肿瘤内，5-ALA 阳性区域的 MIB-1 LI 明显高于非荧光区域。
数据表明，5-ALA 是一种有前途的标志物，可用于术中可视化磁共振成像上无明显增强的弥漫浸润性神经胶质瘤中的间变灶。5-ALA 不受术中脑移位的影响，可提高肿瘤切除过程中组织取样的精度，用于组织学分级，从而优化辅助治疗患者的分配。
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