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Taylor Nayman, Debra Meghan Sanft, Rafaela Amade, Sultan Aldrees, Evangelina Esposito, Miguel N Burnier; C-Kit Expression in an Animal Model of Uveal Melanoma Mirrors That of Humans. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4106.
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© ARVO (1962-2015); The Authors (2016-present)
C-Kit is a prognostic marker that is expressed in human uveal melanoma (UM), but has not yet been studied in animal models. Herein, we sought to confirm that a UM rabbit model, which is the gold standard method to reflect human disease, expresses this marker in both primary and metastatic UM.
The animal model consisted of 14 rabbit eyes injected with human UM cells (92.1 cell line) into the suprachoroidal space, as has been previously described. Eleven metastatic specimens (lung or liver) from these animals were also studied. All specimens were formalin-fixed paraffin embedded. Primary and metastatic samples were stained for C-Kit using a monoclonal antibody using a fully automated immunostaining protocol. C-Kit staining in primary UM was evaluated as 0 for negative, low (<50% of cells), or high (>50% of cells), as per our original study in human UM specimens. A Chi square test was used to compare expression in human and animal samples. The Student’s t-test was used to compare expression in animal primary and metastatic samples to determine whether they showed similar staining.
In the animal model, 11 of 14 eyes had tumors. Of these, 81.8% showed positivity for C-Kit, 33.3% of which showed high expression. Metastatic tumors showed 90.9% positivity for C-Kit, with 30% demonstrating high expression. Compared to expression in human UMs (C-kit positive=78.2%, with high expression=46.5%), Chi square was 0.932 (P=0.3342) for C-Kit, showing that animal and human expression were not statistically different. Similarly, t-tests between primary and secondary UM from the rabbit model for C-Kit were also comparable (P=0.7477).
The similar staining patterns between human UM eyes and our UM rabbit model suggests that the rabbit model is an accurate reflection of the human disease. Moreover, the animal model reflects the intraocular and metastatic staining patterns seen in patients, and thus is an adequate method to study possible therapeutic targets in UM, such as Imatinib Mesylate (Gleevec) which is a potent C-Kit inhibitor.
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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