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 alpha (PDGFR-alpha) and beta (PDGFR-beta). 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-beta 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-beta expression. Since malignant melanoma expresses PTK, it may be a candidate for treatment with anti-PTK, such as STI-571 (Gleevec).
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 alpha (PDGFR-alpha) and beta (PDGFR-beta). 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-beta 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-beta expression. Since malignant melanoma expresses PTK, it may be a candidate for treatment with anti-PTK, such as STI-571 (Gleevec).
Authors: James V Neiswender; Robert L Kortum; Caitlin Bourque; Melissa Kasheta; Leonard I Zon; Deborah K Morrison; Craig J Ceol Journal: Cancer Res Date: 2017-09-25 Impact factor: 12.701
Authors: Jonathan L Curry; Michael A Davies; Tiffany L Calderone; Katherine Nathanson; Victor G Prieto; Jeffrey E Gershenwald Journal: Methods Mol Biol Date: 2014
Authors: Carlos A Torres-Cabala; Wei-Lien Wang; Jonathan Trent; Dan Yang; Su Chen; John Galbincea; Kevin B Kim; Scott Woodman; Michael Davies; Jose A Plaza; J W Nash; Victor G Prieto; Alexander J Lazar; Doina Ivan Journal: Mod Pathol Date: 2009-08-28 Impact factor: 7.842