成人 IDH 野生型低级别胶质瘤应进一步分层。
Adult IDH wild-type lower-grade gliomas should be further stratified.
机构信息
Department of Anatomical and Cellular Pathology, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China); Department of Pathology, Huashan Hospital, Fudan University, Shanghai, China.
出版信息
Neuro Oncol. 2017 Oct 1;19(10):1327-1337. doi: 10.1093/neuonc/nox078.
BACKGROUND
Astrocytoma of the isocitrate dehydrogenase (IDH) wild-type gene is described as a provisional entity within the new World Health Organization (WHO) classification. Some groups believe that IDH wild-type lower-grade gliomas, when interrogated for other biomarkers, will mostly turn out to be glioblastoma. We hypothesize that not all IDH wild-type lower-grade gliomas have very poor outcomes and the group could be substratified prognostically.
METHODS
Seven hundred and eighteen adult WHO grades II and III patients with gliomas from our hospitals were re-reviewed and tested for IDH1/2 mutations. One hundred and sixty-six patients with IDH wild-type cases were identified for further studies, and EGFR and MYB amplifications, mutations of histone H3F3A, TERT promoter (TERTp), and BRAF were examined.
RESULTS
EGFR amplification, BRAF, and H3F3A mutations were observed in 13.8%, 6.9%, and 9.5% of patients, respectively, in a mutually exclusive pattern in IDH wild-type lower-grade gliomas. TERTp mutations were detected in 26.8% of cases. Favorable outcome was observed in patients with young age, oligodendroglial phenotype, and grade II histology. Independent adverse prognostic values of older age, nontotal resection, grade III histology, EGFR amplification, and H3F3A mutation were confirmed by multivariable analysis. Tumors were further classified into "molecularly" high grade (harboring EGFR, H3F3A, or TERTp) (median overall survival = 1.23 y) and lower grade (lacking all of the 3) (median overall survival = 7.63 y) with independent prognostic relevance. The most favorable survival was noted in molecularly lower-grade gliomas with MYB amplification.
CONCLUSION
Adult IDH wild-type lower-grade gliomas are prognostically heterogeneous and do not have uniformly poor prognosis. Clinical information and additional markers, including MYB, EGFR, TERTp, and H3F3A, should be examined to delineate discrete favorable and unfavorable prognostic groups.
背景
在新的世界卫生组织（WHO）分类中，描述 IDH 野生型星形细胞瘤为一种暂定实体。一些研究组认为，当对 IDH 野生型低级别胶质瘤进行其他生物标志物检测时，大多数情况下会被归类为胶质母细胞瘤。我们假设并非所有 IDH 野生型低级别胶质瘤预后都很差，该群体可以进行预后分层。
方法
我们重新回顾和检测了来自医院的 718 名成人 WHO 分级 II 和 III 级胶质瘤患者的 IDH1/2 突变情况。确定了 166 例 IDH 野生型病例进行进一步研究，并检查了 EGFR 扩增、MYB 扩增、组蛋白 H3F3A 突变、TERT 启动子（TERTp）和 BRAF 突变。
结果
在 IDH 野生型低级别胶质瘤中，EGFR 扩增、BRAF 和 H3F3A 突变分别以 13.8%、6.9%和 9.5%的比例出现，呈相互排斥的模式。TERTp 突变在 26.8%的病例中被检测到。在年龄较小、少突胶质细胞表型和 II 级组织学的患者中观察到良好的预后。多变量分析证实，年龄较大、非全切除、III 级组织学、EGFR 扩增和 H3F3A 突变是独立的预后不良因素。肿瘤进一步分为“分子上”高级别（存在 EGFR、H3F3A 或 TERTp）（中位总生存期=1.23 年）和低级别（缺乏所有 3 种）（中位总生存期=7.63 年），具有独立的预后相关性。在分子上低级别胶质瘤中，存在 MYB 扩增的患者具有最佳的生存情况。
结论
成人 IDH 野生型低级别胶质瘤的预后存在异质性，并非预后均差。应检查临床信息和其他标志物，包括 MYB、EGFR、TERTp 和 H3F3A，以描绘出明确的有利和不利预后组。
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