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Luiza Abreu Minussi, Carlos Augusto Moreira, Juliana Portella Passos, Silvin Bakalian, Filipe Muccioli, Miguel N Burnier; Expression of Several Melanoma Markers in a Uveal Melanoma Animal Model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4107.
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© ARVO (1962-2015); The Authors (2016-present)
Animal models are important tools for the advancement of medicine, serving as a basis to evaluate new prognostic and diagnostic criteria and to evaluate treatment efficacy. Uveal melanoma is an intraocular tumor with limited treatment options. Currently, a xenograft rabbit model is the gold standard for evaluating the efficacy of new treatments. The goal of this study is to evaluate the expression of well-established prognostic and diagnostic markers in human uveal melanoma, including Melan-A, Tyrosinase, SOX10, S100 and HMB-45, in a rabbit model.
Uveal melanoma primary tumors from rabbits that were previously injected with a human uveal melanoma cell line in the suprachoroidal space were evaluated. Immunohistochemistry was performed for all rabbit samples with monoclonal antibodies specific for each marker (Melan-A, Tyrosinase, SOX10, S100, and HMB-45). For Melan-A and Tyrosinase, a sample was considered positive if >10% of tumor cells stained. For SOX10, the score was based on nuclear and cytoplasmic expression: 0 for negative, diffuse (positive) when > 50% of tumor cells stained, and focal if <50% stained; For S100 and HMB-45, the intensity of the immunohistochemical reaction was graded on a scale of 0 to 3. To compare between human and rabbit tumor staining, Chi-square or Fisher’s exact test were used as appropriate.
SOX-10 (n=11) was the most sensitive marker of uveal melanoma in the rabbit model: 9 (81%) were classified as “diffuse” and 2 (19%) as “focal”. For HMB-45 (n=14), 1 was classified as grade 0; 1 as grade 2; and 11 grade 3. For S100 (n=13), 3 were grade 1; 9 were grade 2; and 1 was grade 3. For Melan-A (n=12), 9 were positive and 3 were negative. Finally, 13 were positive and 3 were negative for Tyrosinase. The expression pattern of all markers evaluated were similar to their human counterparts (P>0.05 for all).
Animal models play an important role in drug development and for testing drug efficacy. The best models accurately reflect the human condition with similar disease progression, prognostic and diagnostic patterns. Herein, we showed that the expression of five important prognostic markers in uveal melanoma (Melan-A, Tyrosinase, HMB-45, SOX10 and S100) do not differ in an animal model of this disease. Our results confirm the applicability of this model, and warrant its continued use in future uveal melanoma drug efficacy studies.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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