Schittenhelm J, Beschorner R, Simon P, Tabatabai G, Herrmann C, Schlaszus H, Capper D, Weller M, Meyermann R, Mittelbronn M
Institute of Brain Research, University of Tuebingen, Tuebingen, Germany.
Neuropathol Appl Neurobiol. 2009 Feb;35(1):69-81. doi: 10.1111/j.1365-2990.2008.00957.x. Epub 2008 May 7.
Currently, clinical trials using WT1 (Wilms tumour gene) peptide vaccines are conducted in haematopoietic malignancies and solid cancers. Single reports showed that the Wilms tumour gene product WT1 is also expressed in astrocytic neoplasms. Our aim was to investigate WT1 expression in a large cohort of various neuroepithelial tumours of different World Health Organization (WHO) grades and in normal central nervous system (CNS) tissue specimens to test its potential value as a diagnostic marker.
Specimens were assessed by RT-PCR, Western blotting and immunohistochemistry. The samples investigated in our study consisted of 334 human neuroepithelial tumours, among those 33 oligodendrogliomas, 219 astrocytomas (including 105 glioblastomas) and 47 ependymomas.
Our results showed a de novo WT1 expression in neuroepithelial tumours. In diffuse astrocytomas and ependymomas, WT1 expression increased significantly with the grade of malignancy. In contrast, no significant difference was seen between WHO grade-II and -III oligodendrogliomas. Controlling for WHO grade, the comparison of oligodendrogliomas with ependymal and astrocytic tumours showed higher expression values for the latter.
Our study shows that WT1 is expressed de novo in numerous neuroepithelial tumours and increases with the grade of malignancy. These results suggest an important role of WT1 in tumourigenesis and progression in human brain tumours.
目前,使用WT1(威尔姆斯瘤基因)肽疫苗的临床试验正在血液系统恶性肿瘤和实体癌中开展。个别报告显示,威尔姆斯瘤基因产物WT1在星形细胞瘤中也有表达。我们的目的是在一大组世界卫生组织(WHO)不同分级的各种神经上皮肿瘤以及正常中枢神经系统(CNS)组织标本中研究WT1的表达情况,以测试其作为诊断标志物的潜在价值。
通过逆转录聚合酶链反应(RT-PCR)、蛋白质免疫印迹法和免疫组织化学对标本进行评估。我们研究中所调查的样本包括334例人类神经上皮肿瘤,其中有33例少突胶质细胞瘤、219例星形细胞瘤(包括105例胶质母细胞瘤)和47例室管膜瘤。
我们的结果显示神经上皮肿瘤中存在WT1的从头表达。在弥漫性星形细胞瘤和室管膜瘤中,WT1表达随恶性程度显著增加。相比之下,WHO二级和三级少突胶质细胞瘤之间未见显著差异。在控制WHO分级的情况下,少突胶质细胞瘤与室管膜瘤和星形细胞瘤的比较显示,后两者的表达值更高。
我们的研究表明,WT1在众多神经上皮肿瘤中从头表达,并随恶性程度增加。这些结果提示WT1在人脑肿瘤的发生和进展中起重要作用。