WILMS-TUMOR-1 SUSCEPTIBILITY (WT1) GENE-PRODUCTS ARE SELECTIVELY EXPRESSED IN MALIGNANT MESOTHELIOMA

The distinction between malignant Mesothelioma and other neoplastic pr ocesses involving the pleura is difficult, partly due to the lack of s pecific markers expressed on mesothelioma. Because of evidence suggest ing that the Wilms' tumor susceptibility gene (WT1), unlike other tumo r suppressor genes, is restricted mostly to mesenchymally derived tiss ues, we hypothesized that the WT1 gene products could serve as a poten tial marker for mesothelioma. The expression of WT1 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 lu ng cancer specimens, WT1 mRNA was detectable by Northern analysis in 1 6 of 19 mesothelioma cell lines and in 5 of 8 malignant mesothelioma t umors. In contrast, WT1 mRNA was not detected by Northern analysis in non-small cell lung cancer lines or carcinomas. Immunoprecipitation wi th an anti-WT1 monoclonal antibody showed that a 52- to 54-kd protein was present in 4 mesothelioma cell lines. Immunostaining with this ant ibody localized the WT1 protein to the nucleus in two mesothelioma lin es and in 20 of 21 mesothelioma tumors examined. This distinctive patt ern of nuclear immunoreactivity was absent in 26 non-mesothelioma tumo rs involving the lung, including 20 non-small cell lung carcinomas. Th e detection of WT1 mRNA or protein may thus provide a specific molecul ar or immunohistochemical marker for differentiation of mesothelioma f rom other pleural tumors, in particular, adenocarcinoma.