title: Characterization of ocular and metastatic uveal melanoma in an animal model.
abstract: OBJECTIVE
  To characterize, in detail, tumor development, malignant cell dissemination, and metastasis in a 10-week animal model of uveal melanoma.
  
  
  METHODS
  One million 92.1 human primary uveal melanoma cells were injected into the suprachoroidal space of the right eye of 27 immunosuppressed albino rabbits. Intraocular tumor growth was monitored weekly by fundoscopy and by ultrasonography at the end of the experiment. To document the progression of the disease, one animal per week was killed. The enucleated eyes, lungs, and livers were macroscopically examined and histopathologically studied by hematoxylin and eosin, periodic acid-Schiff, and immunohistochemistry. Mononuclear layers isolated from the rabbits' blood samples were cultured.
  
  
  RESULTS
  Histopathology showed intraocular tumors in 89% of the animals. Tumor growth was found 1 week after cell inoculation, and by the end of the experiment large tumor masses were observed. Microscopic pulmonary metastatic foci were first observed 4 weeks after cell injection. By the end of the experiment, all the animals had metastasis to the lungs. Interestingly, 18% of the animals also had micrometastasis to the liver. Viable adherent uveal melanoma cells were successfully isolated from peripheral blood and grown in vitro.
  
  
  CONCLUSIONS
  In this study, most rabbits developed intraocular tumors followed by lung metastasis, and some of these rabbits later developed liver micrometastases. This novel source of research material warrants a follow-up longer than 10 weeks to further explore the pathophysiologic bases of liver involvement commonly encountered in humans. The success in the isolation and culture of circulating malignant cells in this animal model suggests that it might be worthwhile to explore the application of this technique to the management of patients with primary uveal melanoma.
authors.affiliation: Henry C. Witelson Ophthalmic Pathology Laboratory and Registry, McGill University Health Center, Montreal, Quebec, Canada. paublanco@gmail.com
authors.forename: Paula L
authors.initials: PL
authors.lastname: Blanco
authors.forename: Jean Claude A
authors.initials: JC
authors.lastname: Marshall
authors.forename: Emilia
authors.initials: E
authors.lastname: Antecka
authors.forename: Sonia A
authors.initials: SA
authors.lastname: Callejo
authors.forename: Joao P
authors.initials: JP
authors.lastname: Souza Filho
authors.forename: Vinicius
authors.initials: V
authors.lastname: Saraiva
authors.forename: Miguel N
authors.initials: MN
authors.lastname: Burnier
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D008113:Liver Neoplasms / Q000556:secondary*; D008175:Lung Neoplasms / Q000556:secondary*; D008297:Male; D008545:Melanoma / Q000556:secondary* / Q000648:ultrastructure; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D011817:Rabbits; D014604:Uveal Neoplasms / Q000473:pathology* / Q000648:ultrastructure