Department of Neuropathology, Institute of Pathology and Neuropathology, University of Tübingen, Tübingen, Germany.
Department of Neuroradiology, University of Tübingen, Tübingen, Germany.
J Clin Pathol. 2014 Jul;67(7):556-61. doi: 10.1136/jclinpath-2013-202114. Epub 2014 Mar 7.
The zinc finger transcription factor WT1 is expressed in astrocytic neoplasms and therefore is a potential target of immunotherapy in brain tumours. Our aim was to further elucidate the role of WT1 as a diagnostic and prognostic marker in neuropathology, particularly as to the differentiation of astrocytoma from oligodendroglioma as well as to the dependency of WT1 expression on clinically relevant parameters.
829 evaluable brain tumour samples were investigated by WT1 immunohistochemistry on full tissue routine slides, consisting of 442 glioblastomas, 303 astrocytomas, 41 oligodendrogliomas and 43 oligoastrocytomas. In addition public WT1 gene expression data of 351 gliomas were analysed.
Our data show that WT1 expression in diffuse astrocytic tumours increases with WHO tumour grade and is associated with older age, absence of IDH1 mutation but not related to O(6)- methyl guanine methyl transferase (MGMT) promoter methylation status. Univariable, but not multivariable survival analysis indicates that WT1 expression is associated with worse outcome in patients with diffuse astrocytoma but not glioblastoma.
The significant WT1 expression differences between diffuse astrocytomas, oligoastrocytomas and oligodendrogliomas, which are also present in the Repository for Molecular Brain Neoplasia Data, National Cancer Institute (REMBRANDT, 2005, http://rembrandt.nci.nih.gov) gene database set, provide a rationale for use of WT1 as part of a routine immunohistochemistry panel.
锌指转录因子 WT1 在神经胶质瘤中表达，因此是脑肿瘤免疫治疗的潜在靶点。我们的目的是进一步阐明 WT1 作为神经病理学中的诊断和预后标志物的作用，特别是在星形细胞瘤与少突胶质细胞瘤的鉴别以及 WT1 表达对临床相关参数的依赖性方面。
对 829 例可评估的脑肿瘤标本进行 WT1 免疫组化全组织常规切片检测，包括 442 例胶质母细胞瘤、303 例星形细胞瘤、41 例少突胶质细胞瘤和 43 例少突星形细胞瘤。此外，还分析了 351 例胶质瘤的公共 WT1 基因表达数据。
我们的数据表明，弥漫性星形细胞瘤中 WT1 的表达随着 WHO 肿瘤分级的增加而增加，与年龄较大、IDH1 突变缺失有关，但与 O(6)-甲基鸟嘌呤甲基转移酶（MGMT）启动子甲基化状态无关。单变量但不是多变量生存分析表明，WT1 表达与弥漫性星形细胞瘤患者的预后不良相关，但与胶质母细胞瘤无关。
弥漫性星形细胞瘤、少突星形细胞瘤和少突胶质细胞瘤之间存在显著的 WT1 表达差异，这在国家癌症研究所的分子脑肿瘤数据库（REMBRANDT，2005 年，http://rembrandt.nci.nih.gov）中也存在，这为将 WT1 作为常规免疫组化检测的一部分提供了依据。
