WT-1 expression in a spectrum of melanocytic lesions: Implication for differential diagnosis

A previous in vitro study revealed that Wilms's tumor 1 (WT-1) transcripts were detectable in 7 of 9 melanoma cell lines, but not in any of 5-normal melanocyte strains tested. Our current study assessed the expression levels of WT-1 protein in clinical samples, to determine whether the expression levels of the WT-1 protein may be used as a novel marker to assist differential diagnosis. Paraffin-embedded tissue sections from 15 cases of malignant melanomas and 25 cases of benign nevi were subjected to immunohistochemistry with a monoclonal antibody against the human WT-1 protein. The expression levels of WT-1 protein among normal, benign, and malignant melanocytes were semi-quantitatively assessed. Strong and uniform WT-1 immunoreactivities were seen in all or nearly all tumor cells in both the junctional and dermal components of all malignant melanomas, and also in a vast majority of the tumor cells of Spitz's (n = 8), recurrent (n = 2), and junction (n = 2) nevi. Distinct WT-1 immunoreactivities were also seen in some isolated individual tumor cells or tumor cell clusters in the junctional component of compound nevus (9) and in intradermal nevus (2). It is interesting to note that some isolated normal appearing melanocytes or cell clusters, and all morphologically distinct endothelial cells were strongly positive to WT-1. However, all tumor cells within the dermal component of compound (n = 9) or deep penetrating nevi (n = 1), or capsular nevus inclusion of lymph node (1) were devoid of WT-1 expression. Our findings suggest that the expression level of the WT-1 protein has no significant value in distinguishing between Spitz's nevi and malignant melanoma, but it may be a useful marker in differentiating between benign and malignant melanocytes within the dermal component. Our findings also suggest that aberrant WT-1 expression may have oncogenic properties that promote the initiation and progression of melanocytic lesions.