Abstract
Purpose: :
Uveal melanoma is the most common primary intraocular neoplasm affecting cats and dogs. In dogs, although uveal melanoma destroys the eye, the risk of metastasis is very rare. Feline melanomas progress at a faster rate and are generally considered more invasive and malignant. It has been proposed that uveal melanoma in the cat may be a potential animal model for human uveal melanoma. The purpose of this study was to determine if there were differences in the underlying mechanisms of uveal melanoma oncogenesis and metastasis between cats and dogs. In addition, we compared expression of melanoma-related genes in feline uveal melanoma to previously published reports on gene expression in human uveal melanomas.
Methods: :
Paraffin-embedded samples of canine and feline uveal melanomas were examined for the expression of p53, p21, p16, cyclin D, pAkt, Hsp90, and telomerase, using immunohistochemistry.
Results: :
There were no significant differences in staining patterns between canine and feline samples for p53, p21, or pAkt. However, feline melanoma samples consistently scored higher in staining intensity compared to the canine melanomas. Melanomas originating from cats had significantly higher staining scores for cyclin D, telomerase, and Hsp90 compared to canine melanomas.
Conclusions: :
In the tumors examined, the feline melanomas had staining patterns suggesting increased dysregulation of the cell cycle and telomerase expression compared to the canine melanomas. The observed increased expression of cyclin D in feline melanomas supports published data indicating that increased metastasis and poor prognosis are associated with cyclin D overexpression. In addition, Hsp90 was strongly expressed in feline melanomas, which have a tendency to be more malignant. Hsp90 may have a stabilizing effect on the proliferating cells through telomerase regulation thus promoting tumor progression. Telomerase overexpression in feline melanomas could be an underlying mechanism for the aggressive behavior of these tumors. Expression patterns for cyclin D, Hsp 90, and telomerase in feline melanomas are similar to patterns observed in human uveal melanomas. This study indicates that feline uveal melanoma may be a good model for human uveal melanoma.
Keywords: melanoma • immunohistochemistry