Abstract:
Background: The usefulness of 5-ALA-mediated fluorescence-guided resection (FGR) in meningiomas is controversial, and information on the molecular background of fluorescence is sparse. Methods: Specimens obtained during 44 FGRs of intracranial meningiomas were analyzed for the presence of tumor tissue and fluorescence. Protein/mRNA expression of key transmembrane transporters/enzymes involved in PpIX metabolism (ABCB6, ABCG2, FECH, CPOX) were investigated using immunohistochemistry/qPCR. Results: Intraoperative fluorescence was observed in 70 of 111 specimens (63%). No correlation was found between fluorescence and the WHO grade (p = 0.403). FGR enabled the identification of neoplastic tissue (sensitivity 84%, specificity 67%, positive and negative predictive value of 86% and 63%, respectively, AUC: 0.75, p < 0.001), and was improved in subgroup analyses excluding dura specimens (86%, 88%, 96%, 63% and 0.87, respectively; p < 0.001). No correlation was found between cortical fluorescence and tumor invasion (p = 0.351). Protein expression of ABCB6, ABCG2, FECH and CPOX was found in meningioma tissue and was correlated with fluorescence (p < 0.05, each), whereas this was not confirmed for mRNA expression. Aberrant expression was observed in the CNS. Conclusion: FGR enables the intraoperative identification of meningioma tissue with limitations concerning dura invasion and due to ectopic expression in the CNS. ABCB6, ABCG2, FECH and CPOX are expressed in meningioma tissue and are related to fluorescence.
摘要:
背景:5-ALA介导的荧光引导切除术(FGR)在脑膜瘤中的有效性存在争议,和荧光的分子背景信息是稀疏的。
方法:分析了在44个颅内脑膜瘤FGR期间获得的样本中是否存在肿瘤组织和荧光。参与PpIX代谢的关键跨膜转运蛋白/酶的蛋白/mRNA表达(ABCB6,ABCG2,FECH,使用免疫组织化学/qPCR研究CPOX)。
结果:在111个标本中观察到70个(63%)的术中荧光。在荧光和WHO等级之间没有发现相关性(p=0.403)。FGR能够识别肿瘤组织(灵敏度84%,特异性67%,阳性和阴性预测值分别为86%和63%,分别,AUC:0.75,p&lt;0.001),并且在不包括硬脑膜标本的亚组分析中得到了改善(86%,88%,96%,分别为63%和0.87;p<0.001)。皮质荧光与肿瘤侵袭无相关性(p=0.351)。在脑膜瘤组织中发现ABCB6,ABCG2,FECH和CPOX的蛋白表达,并与荧光相关(p<0.05,每个)。而mRNA的表达没有得到证实。在CNS中观察到异常表达。
结论:FGR能够在术中鉴定脑膜瘤组织,其局限性在于硬脑膜浸润和中枢神经系统中的异位表达。ABCB6,ABCG2,FECH和CPOX在脑膜瘤组织中表达,并与荧光有关。