WT1 expression in normal and neoplastic cranial and peripheral nerves is independent of grade of malignancy

Schittenhelm J, Jens Schittenhelm, Thiericke J, John Thiericke, Nagel C, Christoph Nagel, Richard Meyermann, Meyermann R, Rudi Beschorner, Beschorner R
Cancer biomarkers : section A of Disease markers · 2010 · vol. 7(2) , pp. 73–7 · doi:10.3233/cbm-2010-0149 · PMID:21178265 · PMC12922876
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This study found that WT1 protein expression is present in normal peripheral nerves and all types of peripheral nerve sheath tumors, remaining independent of malignancy grade or tumor growth extension.

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This study investigated the immunohistochemical expression of Wilms’ tumor protein (WT1) in 101 samples comprising normal nerves and various peripheral nerve sheath tumors, including schwannomas, neurofibromas, and malignant peripheral nerve sheath tumors. The researchers found that WT1 is present in the majority of normal human nerves and is consistently expressed in the cytoplasm of neoplastic cells across all tumor types analyzed. Notably, the level of WT1 expression was determined to be independent of tumor malignancy grade, growth extension, or the presence of neurocutaneous disorders such as neurofibromatosis. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

OBJECTIVE: Wilms' tumor protein (WT1) expression is usually absent in normal glial cells of the CNS but is highly upregulated in brain tumor cells and its expression correlates with tumor grade. However, knowledge on WT1 expression in tumors of the peripheral nerve system (PNS) is limited. As WT1 antibodies not only serve as biomarker for cancerous tissue but also are considered for cancer immunotherapy, knowledge of WT1 expression in tumorous and normal peripheral nerve tissue is important for therapeutical purposes. METHODS: We analyze the immunohistochemical expression of WT1 in 101 samples consisting of 13 normal nerves, 10 neurofibromas, 69 schwannomas and 9 malignant peripheral nerve sheath tumors (MPNST). Tumor samples included 14 specimen from patients with a proven neurocutaneous disorder (neurofibromatosis type 1 and 2) and 3 cases of schwannomatosis. In 50 vestibular schwannomas tumor growth extension was correlated to WT1 expression. RESULTS: WT1 expression is present in Schwann cells of the majority of normal human nerves (11/13). In peripheral nerve sheath tumors, cytoplasmic WT1 protein is expressed in the cytoplasm of the neoplastic cells in all tumors, including MPNST, neurofibromas and schwannomas. The WT1 expression is independent of tumor malignancy or tumor growth extension and is not associated with a neurocutaneous disorder. CONCLUSION: WT1 expression in normal and neoplastic tissue differs in the peripheral and the central nervous system. These findings may point to a different functional role of WT1 in the PNS and the CNS.
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Abstract

Objective: Wilms’ tumor protein (WT1) expression is usually absent in normal glial cells of the CNS but is highly upregulated in brain tumor cells and its expression correlates with tumor grade. However, knowledge on WT1 expression in tumors of the peripheral nerve system (PNS) is limited. As WT1 antibodies not only serve as biomarker for cancerous tissue but also are considered for cancer immunotherapy, knowledge of WT1 expression in tumorous and normal peripheral nerve tissue is important for therapeutical purposes.

Methods

We analyze the immunohistochemical expression of WT1 in 101 samples consisting of 13 normal nerves, 10 neurofibromas, 69 schwannomas and 9 malignant peripheral nerve sheath tumors (MPNST). Tumor samples included 14 specimen from patients with a proven neurocutaneous disorder (neurofibromatosis type 1 and 2) and 3 cases of schwannomatosis. In 50 vestibular schwannomas tumor growth extension was correlated to WT1 expression.

Results

WT1 expression is present in Schwann cells of the majority of normal human nerves (11/13). In peripheral nerve sheath tumors, cytoplasmic WT1 protein is expressed in the cytoplasm of the neoplastic cells in all tumors, including MPNST, neurofibromas and schwannomas. The WT1 expression is independent of tumor malignancy or tumor growth extension and is not associated with a neurocutaneous disorder.

Conclusion

WT1 expression in normal and neoplastic tissue differs in the peripheral and the central nervous system. These findings may point to a different functional role of WT1 in the PNS and the CNS.

Keywords

WT1, MPNST, schwannoma, neurofibroma Full Text The Full Text of this article is available as a PDF (1.4 MB).

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MeSH descriptors

Cranial Nerve Neoplasms Cranial Nerves Nerve Sheath Neoplasms Peripheral Nerves WT1 Proteins Adolescent Adult Aged Case-Control Studies Child Cranial Nerve Neoplasms Cranial Nerve Neoplasms Cranial Nerves Female Humans Male Middle Aged Nerve Sheath Neoplasms Nerve Sheath Neoplasms Neurilemmoma

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