title: The role of c-kit and imatinib mesylate in uveal melanoma.
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 10 microM).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil. patriciarusa@yahoo.com.br
authors.forename: Patricia Rusa
authors.initials: PR
authors.lastname: Pereira
authors.forename: Alexandre Nakao
authors.initials: AN
authors.lastname: Odashiro
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Marshall
authors.forename: Zelia Maria
authors.initials: ZM
authors.lastname: Correa
authors.forename: Rubens
authors.initials: R
authors.lastname: Belfort
authors.forename: Miguel N
authors.initials: MN
authors.lastname: Burnier