WT1 mutation in malignant mesothelioma and WT1 immunoreactivity in relation to p53 and growth factor receptor expression, cell-type transition, and prognosis.

The Wilms tumour 1 (WT1) gene is believed to contribute to the growth and differentiation of certain tissues, including mesothelium. This study assessed WT1 gene status by mutational screening in 42 malignant mesotheliomas (MMs) and 3 MM cell lines and detected two tumours with identical heterozygous single nucleotide deletions in intron 7, with no apparent consequence for WT1 function. Furthermore, the expression pattern of the WT1 gene was studied in MMs and related lesions using three anti-WT1 monoclonal antibodies (MAbs). Strong to moderate nuclear immunoreactivity was noted in MM in situ (54/56), cultured mesothelioma cells (4/5), and hyperplastic and normal pleural (non-neoplastic, NNM) specimens. WT1 immunoreactivity was absent in all primary tumours of lung and in pleural metastases from adenocarcinomas of breast and colon; immunoreactivity was present in pleural metastases from renal carcinomas, melanomas, and papillary carcinomas of the ovary. Expression of the WT1 protein in MM was not correlated with survival. Coordinate expression of the WT1 protein and its putative transcriptional target genes was determined by correlating WT1 immunostaining with epidermal growth factor receptor (EGF-R) and insulin-like growth factor 1 receptor (IGF-1R) expression on MM and NNM; no significant correlation was found, irrespective of p53 expression status. Finally, the putative involvement of WT1 in cell-type transition was supported by this study, in that epithelial mesothelioma showed the strongest WT1 immunoreactivity while sarcomatous mesothelioma showed the least.