WT1 expression increases with malignancy and indicates unfavourable outcome in astrocytoma.

Abstract

AIMS:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Julian Rauscher, Rudi Beschorner, Midea Gierke, Sotirios Bisdas, Christian Braun, Florian H Ebner, Jens Schittenhelm
• Journal: Journal of clinical pathology (J Clin Pathol) Vol. 67 Issue 7 Pg. 556-61 (Jul 2014) ISSN: 1472-4146 [Electronic] England
• PMID: 24607494 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Chemical References

• Biomarkers, Tumor
• Tumor Suppressor Proteins
• WT1 Proteins
• WT1 protein, human
• Isocitrate Dehydrogenase
• IDH1 protein, human
• DNA Modification Methylases
• MGMT protein, human
• DNA Repair Enzymes

Topics

• Adolescent
• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Astrocytoma (chemistry, genetics, mortality, pathology, therapy)
• Biomarkers, Tumor (analysis, genetics)
• Brain Neoplasms (chemistry, genetics, mortality, pathology, therapy)
• Child
• Child, Preschool
• DNA Methylation
• DNA Modification Methylases (genetics)
• DNA Mutational Analysis
• DNA Repair Enzymes (genetics)
• Databases, Genetic
• Female
• Genes, Wilms Tumor
• Genetic Predisposition to Disease
• Humans
• Immunohistochemistry
• Infant
• Isocitrate Dehydrogenase (genetics)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Mutation
• Neoplasm Grading
• Oligodendroglioma (chemistry, genetics, mortality, pathology, therapy)
• Phenotype
• Polymerase Chain Reaction
• Predictive Value of Tests
• Prognosis
• Promoter Regions, Genetic
• Risk Factors
• Tissue Array Analysis
• Tumor Suppressor Proteins (genetics)
• Up-Regulation
• WT1 Proteins (analysis, genetics)
• Young Adult