Jaber Mohammed, Wölfer Johannes, Ewelt Christian, Holling Markus, Hasselblatt Martin, Niederstadt Thomas, Zoubi Tarek, Weckesser Matthias, Stummer Walter
‡Department of Neurosurgery, University Hospital Münster, Münster, Germany;§Institute of Neuropathology, University Hospital Münster, Münster, Germany;¶Institute for Clinical Radiology, University Hospital of Münster, Münster, Germany;‖Department of Nuclear Medicine, University Hospital of Münster, Münster, Germany.
Neurosurgery. 2016 Mar;78(3):401-11; discussion 411. doi: 10.1227/NEU.0000000000001020.
Approximately 20% of grade II and most grade III gliomas fluoresce after 5-aminolevulinic acid (5-ALA) application. Conversely, approximately 30% of nonenhancing gliomas are actually high grade.
The aim of this study was to identify preoperative factors (ie, age, enhancement, 18F-fluoroethyl tyrosine positron emission tomography [F-FET PET] uptake ratios) for predicting fluorescence in gliomas without typical glioblastomas imaging features and to determine whether fluorescence will allow prediction of tumor grade or molecular characteristics.
Patients harboring gliomas without typical glioblastoma imaging features were given 5-ALA. Fluorescence was recorded intraoperatively, and biopsy specimens collected from fluorescing tissue. World Health Organization (WHO) grade, Ki-67/MIB-1 index, IDH1 (R132H) mutation status, O-methylguanine DNA methyltransferase (MGMT) promoter methylation status, and 1p/19q co-deletion status were assessed. Predictive factors for fluorescence were derived from preoperative magnetic resonance imaging and F-FET PET. Classification and regression tree analysis and receiver-operating-characteristic curves were generated for defining predictors.
Of 166 tumors, 82 were diagnosed as WHO grade II, 76 as grade III, and 8 as glioblastomas grade IV. Contrast enhancement, tumor volume, and F-FET PET uptake ratio >1.85 predicted fluorescence. Fluorescence correlated with WHO grade (P < .001) and Ki-67/MIB-1 index (P < .001), but not with MGMT promoter methylation status, IDH1 mutation status, or 1p19q co-deletion status. The Ki-67/MIB-1 index in fluorescing grade III gliomas was higher than in nonfluorescing tumors, whereas in fluorescing and nonfluorescing grade II tumors, no differences were noted.
Age, tumor volume, and F-FET PET uptake are factors predicting 5-ALA-induced fluorescence in gliomas without typical glioblastoma imaging features. Fluorescence was associated with an increased Ki-67/MIB-1 index and high-grade pathology. Whether fluorescence in grade II gliomas identifies a subtype with worse prognosis remains to be determined.
应用5-氨基乙酰丙酸（5-ALA）后，约20%的二级胶质瘤和大多数三级胶质瘤会发生荧光反应。相反，约30%无强化的胶质瘤实际上是高级别胶质瘤。
本研究旨在确定术前因素（即年龄、强化情况、18F-氟乙基酪氨酸正电子发射断层扫描[F-FET PET]摄取率），以预测无典型胶质母细胞瘤影像学特征的胶质瘤的荧光反应，并确定荧光是否能够预测肿瘤分级或分子特征。
对患有无典型胶质母细胞瘤影像学特征的胶质瘤患者给予5-ALA。术中记录荧光反应，并从荧光组织中采集活检标本。评估世界卫生组织（WHO）分级、Ki-67/MIB-1指数、异柠檬酸脱氢酶1（IDH1，R132H）突变状态、O-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化状态以及1p/19q共缺失状态。荧光反应的预测因素来自术前磁共振成像和F-FET PET。生成分类与回归树分析以及受试者工作特征曲线以确定预测指标。
166例肿瘤中，82例被诊断为WHO二级，76例为三级，8例为四级胶质母细胞瘤。对比增强、肿瘤体积以及F-FET PET摄取率>1.85可预测荧光反应。荧光反应与WHO分级（P < .001）和Ki-67/MIB-1指数（P < .001）相关，但与MGMT启动子甲基化状态、IDH1突变状态或1p19q共缺失状态无关。三级荧光胶质瘤中的Ki-67/MIB-1指数高于非荧光肿瘤，而在二级荧光和非荧光肿瘤中，未观察到差异。
年龄、肿瘤体积和F-FET PET摄取是预测无典型胶质母细胞瘤影像学特征的胶质瘤中5-ALA诱导荧光反应的因素。荧光反应与Ki-67/MIB-1指数升高和高级别病理相关。二级胶质瘤中的荧光反应是否可识别预后较差的亚型仍有待确定。
