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Am J Pathol. Feb 1995; 146(2): 344–356.
PMCID: PMC1869867

Wilms' Tumor 1 Susceptibility (WT1) Gene Products are Selectively Expressed in Malignant Mesothelioma

Abstract

The distinction between malignant mesothelioma and other neoplastic processes involving the pleura is difficult, partly due to the lack of specific markers expressed on mesothelioma. Because of evidence suggesting that the Wilms' tumor susceptibility gene (WT1), unlike ot her tumor suppressor genes, is restricted mostly to mesenchymaly derived tissues, we hypothesized that the WTI gene products could serve as a potential marker for mesothelioma. The expression of WTI mRNA was analyzed in 19 malignant mesothelioma cell lines and 9 tumors and compared with the expression of WT1 in 10 non-small cell lung cancer lines and 9 lung cancer specimens. WTI mRNA was detectable by Northern analysis in 16 of 19 mesothelioma cell lines and in 5 of 8 malignant mesothelioma tumors. In contrast, WTI mRNA was not detected by Northern analysis in non-small cell lung cancer lines or carcinomas. Immunoprecipitation with an anti-WT1 monoclonal antibody showed that a52-to 54-kdprotein was present in 4 mesothelioma cell lines. Immunostanig with this antibody localizd the WT1 protein to the nucleus in two mesothelioma lines and in 20 of 21 mesothelioma tumors examined. This distinctive pattern of nuclear immunoreactivity was absent in 26 non-mesothelioma tumors involving the lung, including 20 non-small cell lung carcinomas. The detection of WTI mRNA or protein may thus provide a specific molecular or immunohistochemical marker for differentiation of mesothelioma from other pleural tumors, inparticular, adenocarcinoma.

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