Abstract
Purpose: :
Blue irises contain minimal amounts of melanin, a pigment that acts to absorb ultraviolet (UV) light. Ultraviolet–induced cellular damage and malignancy have been shown to be associated with increased expression of gadd45, tumor suppressor gene p53, proliferating cell nuclear antigen (PCNA), telomerase (TERT), and single–stranded DNA (UVssDNA). Immunohistochemistry was used to investigate the cell of origin and influence of UV radiation on the development of spindle cell neoplasms in the anterior uveal tract of blue–eyed dogs.
Methods: :
Light microscopy was performed on 17 neoplasms from the 4,007 canine ocular neoplasms diagnosed at the Comparative Ocular Pathology Laboratory of Wisconsin from 1978 to 2005. Immunohistochemistry was performed to detect alpha–smooth muscle actin (SMA), vimentin, desmin, glial fibrillary acidic protein (GFAP), melan A, microphthalmic transcription factor (MITF–1), gadd45, p53, PCNA, anti–UVssDNA, and anti–human telomerase (TERT).
Results: :
Histologically, all neoplasms were within the anterior uvea. All neoplasms were composed of spindle cells arranged in fascicles and whorls with a variable amount of prominent fibrillar eosinophilic extracellular matrix. All neoplasms were positive for vimentin (10/10) and negative for SMA (8/8), desmin (7/7), melan A (9/9), and MITF–1 (9/9). Staining for GFAP was variable (positive neoplastic cells present in 7/12). Neoplasms were positive as follows: PCNA (8/10 strongly positive, 2/10 weakly positive), gadd45 (3/10 strongly positive, 6/10 weakly positive), p53 (0/10 strongly positive, 3/10 weakly positive), TERT (3/10 strongly positive, 5/10 weakly positive) and UVssDNA (1/10 strongly positive, 5/10 weakly positive).
Conclusions: :
These neoplasms represent a distinctive uveal spindle cell neoplasm of non–melanocytic origin that occurs in dogs with blue iris color. Inconsistent expression of p53, gadd45, anti–UVssDNA, and telomerase suggests that UV–related damage does not play a role in the development of this neoplastic entity. The relationship between spindle cell tumors of the anterior uveal tract of dogs, blue iris color, and UV radiation has not yet been identified.
Keywords: uvea • immunohistochemistry • oncology