Expression of vascular endothelial growth factor in uveal melanoma and its correlation with metastasis

Aims - To evaluate the expression of vascular endothelial growth factor (VEGF) in uveal melanomas and correlate its presence with tumour characteristics and systemic metastasis. Methods - 47 cases of ciliochoroidal melanoma enucleated between 1983 and 1993 were retrieved from the pathology archives at the University of Western Ontario. Paraffin sections stained with haematoxylin and eosin, periodic acid Schiff, and periodic acid Schiff without haematoxylin after bleaching of melanin were examined. The expression of VEGF protein was examined by an immunoalkaline phosphatase method following antigen retrieval, using an antibody to VEGF and vector red as the chromogen. The intensity of VEGF immunoreactivity was graded on a scale of 0-7 and correlated with tumour cell type, tumour size, presence or absence of necrosis, pigmentation, mitotic activity, microvascular density, and microvascular pattern. Results - VEGF immunoreactivity was present in 44/47 tumours (94%): the intensity was graded as very weak (1-2) in 29/47 (62%) and as weak or greater in 15/47 (32%). VEGF was also found in the ciliary epithelium, smooth muscle of the ciliary body and iris, retinal ganglion cells, inner photoreceptor segments, and the retinal pigment epithelium. Follow up data were available in 43/47 patients (91.5%), with a median follow up time of 10 years. 16/43 (37%) patients developed metastases. VEGF expression in melanoma was linked to the presence of tumour necrosis and the degree of pigmentation but no statistically significant relation with microvascular pattern, tumour size, or microvascular density was found. There was no statistically significant correlation between VEGF expression and metastasis. Conclusions - Most ciliochoroidal melanomas express VEGF and expression is correlated with the presence of necrosis but not with the occurrence of systemic metastasis or tumour angiogenesis.