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

J Cutan Pathol. 2003 Oct;30(9):539-47. doi: 10.1034/j.1600-0560.2003.00090.x.


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).

Publication types

  • Comparative Study

MeSH terms

  • Cell Transformation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Melanoma / metabolism*
  • Nevus / metabolism*
  • Platelet-Derived Growth Factor / biosynthesis
  • Precancerous Conditions / metabolism
  • Protein Array Analysis
  • Protein-Tyrosine Kinases / biosynthesis*
  • Proto-Oncogene Proteins c-abl / biosynthesis
  • Proto-Oncogene Proteins c-kit / biosynthesis
  • Proto-Oncogene Proteins c-sis / biosynthesis
  • Skin Neoplasms / metabolism*


  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • platelet-derived growth factor A
  • ARG tyrosine kinase
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-kit
  • Proto-Oncogene Proteins c-abl