可见血啉单甲醚诱导荧光是否是组织学证实（世界卫生组织 2016 年）低级别胶质瘤患者预后的独立生物标志物？
Is Visible Aminolevulinic Acid-Induced Fluorescence an Independent Biomarker for Prognosis in Histologically Confirmed (World Health Organization 2016) Low-Grade Gliomas?
机构信息
Department of Neurosurgery, University Hospital Münster, Münster, Germany.
Institute of Neuropathology, University Hospital Münster, Münster, Germany.
出版信息
Neurosurgery. 2019 Jun 1;84(6):1214-1224. doi: 10.1093/neuros/nyy365.
BACKGROUND
Approximately 20% of low-grade gliomas (LGG) display visible protoporphyrin fluorescence during surgery after 5-aminolevulinic acid (5-ALA) administration.
OBJECTIVE
To determine if fluorescence represents a prognostic marker in LGG.
METHODS
Seventy-four consecutive patients with LGG (World Health Organization 2016) were operated on with 5-ALA. Fluorescent tissue was specifically biopsied. Tumor size, age, Karnofsky index, contrast-enhancement, fluorescence, and molecular factors (IDH1/IDH2-mutations, Ki67/MIB1 Index, 1p19q codeletions, ATRX, EGFR, p53 expression, and O6-methylguanine DNA methyltransferase promotor methylation), were related to progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS).
RESULTS
Sixteen of seventy-four LGGs (21.6%) fluoresced. Fluorescence was partially related to weak enhancement on magnetic resonance imaging and increased (positron emission tomography)PET-FET uptake, but not to Karnofsky Performance Score, tumor size, or age. Regarding molecular markers, only EGFR expression differed marginally (fluorescing vs nonfluorescing: 19% vs 5%; P = .057). Median follow-up was 46.4 mo (95% confidence interval [CI]: 41.8-51.1). PFS, MTFS, and OS were shorter in fluorescing tumors (PFS: median 9.8 mo, 95% CI: 1.00-27.7 vs 45.8, 31.9-59.7, MTFS: 43.0 [27.5-58.5] vs 64.6 [57.7-71.5], median not reached, P = .015; OS: 51.6, [34.8-68.3] vs [68.2, 62.7-73.8], P = .002). IDH mutations significantly predicted PFS, MTFS, and OS. In multivariate analysis IDH status and fluorescence both independently predicted MTFS and OS. PFS was not independently predicted by fluorescence.
CONCLUSION
This is the first report investigating the role of ALA-induced fluorescence in histologically confirmed LGG. Fluorescence appeared to be a marker for inherent malignant transformation and OS, independently of known prognostic markers. Fluorescence in LGG might be taken into account when deciding on adjuvant therapies.
背景
约 20%的低级别胶质瘤（LGG）在接受 5-氨基酮戊酸（5-ALA）治疗后手术中显示可见原卟啉荧光。
目的
确定荧光是否代表 LGG 的预后标志物。
方法
对 74 例连续接受 LGG（世界卫生组织 2016 年）手术的患者进行了 5-ALA 手术。特异性地对荧光组织进行活检。肿瘤大小、年龄、卡诺夫斯基指数、对比增强、荧光以及分子因素（IDH1/IDH2 突变、Ki67/MIB1 指数、1p19q 缺失、ATRX、EGFR、p53 表达和 O6-甲基鸟嘌呤 DNA 甲基转移酶启动子甲基化）与无进展生存期（PFS）、无恶性转化生存期（MTFS）和总生存期（OS）相关。
结果
74 例 LGG 中有 16 例（21.6%）发生荧光。荧光与磁共振成像上的弱增强部分相关，与（正电子发射断层扫描）PET-FET 摄取增加相关，但与卡诺夫斯基表现评分、肿瘤大小或年龄无关。在分子标志物方面，只有 EGFR 表达略有差异（荧光与非荧光：19%与 5%；P=0.057）。中位随访时间为 46.4 个月（95%置信区间 [CI]：41.8-51.1）。荧光肿瘤的 PFS、MTFS 和 OS 更短（PFS：中位数 9.8 个月，95%CI：1.00-27.7 与 45.8、31.9-59.7，MTFS：43.0[27.5-58.5]与 64.6[57.7-71.5]，中位未达到，P=0.015；OS：51.6[34.8-68.3]与 68.2[62.7-73.8]，P=0.002）。IDH 突变显著预测了 PFS、MTFS 和 OS。在多变量分析中，IDH 状态和荧光均独立预测了 MTFS 和 OS。荧光不能独立预测 PFS。
结论
这是第一项调查 ALA 诱导的荧光在组织学证实的 LGG 中的作用的报告。荧光似乎是内在恶性转化和 OS 的标志物，与已知的预后标志物无关。在决定辅助治疗时，LGG 中的荧光可能需要考虑。
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