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胶质纤维酸性蛋白、微管相关蛋白-2、神经生长抑制因子-A、少突胶质细胞髓鞘糖蛋白和波形蛋白在 2016 年 WHO 分类神经上皮肿瘤中的免疫组化比较分析及其预后价值。

Immunohistochemical comparative analysis of GFAP, MAP - 2, NOGO - A, OLIG - 2 and WT - 1 expression in WHO 2016 classified neuroepithelial tumours and their prognostic value.

机构信息

Department of Neuropathology, Institute of Pathology and Neuropathology, University Hospital of Tuebingen, Eberhard Karls University of Tuebingen and Comprehensive Cancer Center Tuebingen-Stuttgart, Tuebingen, 72076, Germany.

Department of Neurosurgery, University Hospital of Tuebingen, Eberhard Karls University Tuebingen, Tuebingen, 72076, Germany.

出版信息

Pathol Res Pract. 2018 Jan;214(1):15-24. doi: 10.1016/j.prp.2017.12.009. Epub 2017 Dec 14.

Abstract

Immunohistochemistry is routinely used in differential diagnosis of tumours of the central nervous system (CNS). The latest 2016 WHO 2016 revision now includes molecular data such as IDH mutation and 1p/19q codeletion thus restructuring glioma classification. Direct comparative information between commonly used immunohistochemical markers for glial tumours GFAP, MAP - 2, NOGO - A, OLIG - 2 and WT - 1 concerning quality and quantity of expression and their relation to the new molecular markers are lacking. We therefore compared the immunohistochemical staining results of all five antibodies in 34 oligodendrogliomas, 106 ependymomas and 423 astrocytic tumours. GFAP expression was reduced in cases with higher WHO grade, oligodendroglial differentiation and in IDH wildtype diffuse astrocytomas. By contrast MAP - 2 expression was significantly increased in diffuse astrocytomas with IDH mutation, while NOGO - A expression was not associated with any molecular marker. WT - 1 expression was significantly decreased in tumours with IDH mutation and ATRX loss. OLIG - 2 was increased in IDH-mutant grade II astrocytomas and in cases with higher proliferation rate. In univariate survival analysis high WT - 1 expression was significantly associated with worse outcome in diffuse astrocytic tumours (log rank p < 0.0001; n = 211; median time: 280 days vs 562 days). None of the markers was prognostic in multivariate survival analysis. Among the evaluated markers MAP - 2, OLIG - 2 and WT - 1 showed the best potential to separate between glioma entities and can be recommended for a standardized immunohistochemical panel.

摘要

免疫组织化学常用于中枢神经系统(CNS)肿瘤的鉴别诊断。最新的 2016 年 WHO 2016 年修订版现在包括 IDH 突变和 1p/19q 缺失等分子数据,从而重构了神经胶质瘤的分类。目前缺乏关于胶质肿瘤常用免疫组织化学标志物(GFAP、MAP-2、NOGO-A、OLIG-2 和 WT-1)在表达质量和数量方面以及与新分子标志物关系的直接比较信息。因此,我们比较了 34 例少突胶质细胞瘤、106 例室管膜瘤和 423 例星形细胞瘤中所有 5 种抗体的免疫组织化学染色结果。在 WHO 分级较高、少突胶质分化和 IDH 野生型弥漫性星形细胞瘤中,GFAP 表达减少。相比之下,MAP-2 表达在 IDH 突变弥漫性星形细胞瘤中显著增加,而 NOGO-A 表达与任何分子标志物均无关。WT-1 表达在 IDH 突变和 ATRX 缺失的肿瘤中显著降低。OLIG-2 在 IDH 突变的 II 级星形细胞瘤和增殖率较高的病例中增加。在单因素生存分析中,WT-1 高表达与弥漫性星形细胞瘤的预后较差显著相关(对数秩检验,p<0.0001;n=211;中位时间:280 天 vs 562 天)。在多因素生存分析中,没有一个标志物具有预后意义。在所评估的标志物中,MAP-2、OLIG-2 和 WT-1 显示出最好的潜力来区分神经胶质瘤实体,可以推荐用于标准化的免疫组织化学组。

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