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 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.


CONCLUSIONS
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).
D002471:Cell Transformation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008545:Melanoma / Q000378:metabolism*; D009506:Nevus / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D011230:Precancerous Conditions / Q000378:metabolism; D040081:Protein Array Analysis; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis*; D016315:Proto-Oncogene Proteins c-abl / Q000096:biosynthesis; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis; D012878:Skin Neoplasms / Q000378:metabolism*
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C075278:platelet-derived growth factor A; C426236:ARG tyrosine kinase; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D016315:Proto-Oncogene Proteins c-abl