Abstract
The human Wilms’ tumor gene (WT1) was originally isolated in a Wilms’ tumor of the kidney as a tumor suppressor gene. Numerous isoforms of WT1, by combination of alternative translational start sites, alternative RNA splicing and RNA editing, have been well documented. During human ontogenesis, according to the antibodies used, anti-C or N-terminus WT1 protein, nuclear expression can be frequently obtained in numerous tissues, including metanephric and mesonephric glomeruli, and mesothelial and sub-mesothelial cells, while cytoplasmic staining is usually found in developing smooth and skeletal cells, myocardium, glial cells, neuroblasts, adrenal cortical cells and the endothelial cells of blood vessels. WT1 has been originally described as a tumor suppressor gene in renal Wilms’ tumor, but more recent studies emphasized its potential oncogenic role in several neoplasia with a variable immunostaining pattern that can be exclusively nuclear, cytoplasmic or both, according to the antibodies used (anti-C or N-terminus WT1 protein). With the present review we focus on the immunohistochemical expression of WT1 in some tumors, emphasizing its potential diagnostic role and usefulness in differential diagnosis. In addition, we analyze the WT1 protein expression profile in human embryonal/fetal tissues in order to suggest a possible role in the development of organs and tissues and to establish whether expression in some tumors replicates that observed during the development of tissues from which these tumors arise.
Highlights
The human Wilms’ tumor gene (WT1), first isolated as a tumor suppressor gene and involved in the development of Wilms’ tumor of the kidney [1], was among the principal tumor suppressor genes to be cloned [2]
Wilms’ Tumor 1 (WT1) protein expression is restricted to the nucleus (Figure 3), even if it can be focally observed in the cytoplasm of the cells of sarcomatoid mesotheliomas [74,75,76,77,78]
These results suggested that WT1 (17AA+) might be a crucial isoform in cancer progression and development, and might work together with WT1 (17AA−) as a protein partner
Summary
The human Wilms’ tumor gene (WT1), first isolated as a tumor suppressor gene and involved in the development of Wilms’ tumor of the kidney [1], was among the principal tumor suppressor genes to be cloned [2]. During human ontogenesis, according to the antibodies used, anti-C or N-terminus WT1 protein, [36,39,40,41,42,43,44,45,46,47], nuclear expression can be frequently obtained in metanephric and mesonephric glomeruli, primary sex cords, gonadic stroma and mesothelial and sub-mesothelial cells, while cytoplasmic staining is usually found in developing skeletal muscles, myocardium, radial glia of the spinal cord and cerebral cortex, sympathetic neuroblasts, adrenal cortical cells and the endothelial cells of blood vessels [33,34,37,38,48,49,50,51,52].
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