Analysis of protein tyrosine kinase expression in melanocytic lesions by tissue array

Background: It has been proposed that melanoma progression involves a multistep process from benign nevi (BN), dysplastic nevi (DN), radial and vertical growth phase melanoma (MM) to metastatic melanoma (MMM). Protein tyrosine kinases (PTKs) may participate in this progression. Methods: Tissue microarray blocks of 89 melanocytic lesions were evaluated by immunohistochemistry for the expression of selected PTKs: c-kit, c-abl, abl-related gene (ARG), platelet-derived growth factor receptors α (PDGFR-α) and β (PDGFR-β). Results: Seventeen of 31 (55%) MMM lacked expression of c-kit versus 100% expression (18/18) in DN and 96% expression (22/23) in MM; similarly, only 59% (10/17) of BN showed expression of c-kit. PDGFR-β expression levels were similar in BN, DN, and MM, but lower in MMM. There was a trend toward lower expression of abl and ARG from BN to MMM. There was a marked decrease in staining intensity of ARG from BN to DN, MM, and MMM. Conclusion: Our results support that BN is different from DN and MM and that these two are different from MMM. Metastasis appears to be associated with loss of c-kit and PDGFR-β expression. Since malignant melanoma expresses PTK, it may be a candidate for treatment with anti-PTK, such as STI-571 (Gleevec).