The role of c-kit and imatinib mesylate in uveal melanoma

Patricia Rusa Pereira, Alexandre Nakao Odashiro, Jean Claude Marshall, Zelia Maria Correa, Rubens Belfort, Miguel N. Burnier

Research output: Contribution to journalArticle

Abstract

Background. Uveal melanoma (UM) is the most common primary intraocular tumor in adults, leading to metastasis in 40% of the cases and ultimately to death in 10 years, despite local and/or systemic treatment. The c-kit protein (CD117) is a membrane-bound tyrosine kinase receptor and its overexpression has been observed in several neoplasms. Imatinib mesylate is a FDA approved compound that inhibits tyrosine quinase receptors, as well as c-kit. Imatinib mesylate controls tumor growth in up to 85% of advanced gastrointestinal stromal tumors, a neoplasia resistant to conventional therapy. Methods. Fifty-five specimens of primary UM selected from the archives of the Ocular Pathology Laboratory, McGill University, Montreal, Canada, were immunostained for c-kit. All cells displaying distinct immunoreactivity were considered positive. Four human UM cell lines and 1 human uveal transformed melanocyte cell line were tested for in vitro proliferation Assays (TOX-6) and invasion assay with imatinib mesylate (concentration of 10μM). Results. The c-kit expression was positive in 78.2% of the UM. There was a statistical significant decrease in the proliferation and invasion rates of all 5 cell lines. Conclusion. The majority of UM expressed c-kit, and imatinib mesylate does decrease the proliferation and invasion rates of human UM cell lines. These results justify the need for a clinical trial to investigate in vivo the response of UM to imatinib mesylate.

Original languageEnglish (US)
Article number19
JournalJournal of Carcinogenesis
Volume4
DOIs
StatePublished - Oct 19 2005

Keywords

  • C-kit
  • CD117
  • Gleevec®
  • Imatinib mesylate
  • Melanoma
  • Ocular
  • Uveal

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Health, Toxicology and Mutagenesis

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  • Cite this

    Pereira, P. R., Odashiro, A. N., Marshall, J. C., Correa, Z. M., Belfort, R., & Burnier, M. N. (2005). The role of c-kit and imatinib mesylate in uveal melanoma. Journal of Carcinogenesis, 4, [19]. https://doi.org/10.1186/1477-3163-4-19