WT1 expression increases with malignancy and indicates unfavourable outcome in astrocytoma

Area of Science:

• Neuro-oncology
• Molecular Pathology
• Immunotherapy

Background:

• The zinc finger transcription factor WT1 is expressed in astrocytic neoplasms, suggesting its potential as an immunotherapy target in brain tumours.
• WT1's role as a diagnostic and prognostic marker in neuropathology requires further elucidation, particularly in differentiating astrocytoma from oligodendroglioma.

Purpose of the Study:

• To investigate the role of WT1 expression as a diagnostic and prognostic marker in astrocytic neoplasms.
• To assess WT1's utility in differentiating astrocytoma from oligodendroglioma.
• To determine the relationship between WT1 expression and clinically relevant parameters in brain tumours.

Main Methods:

• Immunohistochemistry for WT1 was performed on 829 brain tumour samples, including glioblastomas, astrocytomas, oligodendrogliomas, and oligoastrocytomas.
• Public WT1 gene expression data from 351 additional gliomas were analyzed.
• Correlation with WHO tumour grade, age, IDH1 mutation status, and O(6)-methyl guanine methyl transferase (MGMT) promoter methylation was assessed.

Main Results:

• WT1 expression in diffuse astrocytic tumours increases with WHO tumour grade.
• WT1 expression is associated with older age and absence of IDH1 mutation.
• Univariable survival analysis indicated WT1 expression is linked to worse outcomes in diffuse astrocytoma patients, but not glioblastoma patients.

Conclusions:

• Significant differences in WT1 expression exist between diffuse astrocytomas, oligoastrocytomas, and oligodendrogliomas.
• These expression differences are also evident in public gene expression databases.
• WT1 shows potential as a routine immunohistochemistry marker in neuropathology for brain tumour diagnosis and prognosis.