Diagnostic value of WT1 in neuroepithelial tumours

Aims: 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. Methods: 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. Results: 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. Conclusions: 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.