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

Abstract

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. ParaYn sections stained with haematoxylin and eosin, periodic acid SchiV, and periodic acid SchiV 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. (Br J Ophthalmol 2000;84:750-756)

Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS

“…Actin levels were assessed as a loading control. uveal melanoma (Stitt et al, 1998;Sheidow et al, 2000), could operate in cutaneous melanoma as a survival factor through increasing MAPK and PI3K pathway activity. It is possible that MAPK activation is such a crucial requirement for uveal melanoma development because it similarly provides survival, and/or antiapoptotic signals, necessary for tumour cell growth and maintenance.…”

Expression of Vascular Endothelial Growth Factor A, Matrix Metalloproteinase 9 and Extravascular Matrix Patterns in Iris and Ciliary Body Melanomas

“…Newer immunohistopathological markers including VEGF-A, MMP-9 and EMPs have been studied extensively in uveal melanomas [6,[12][13][14][15][16][17][18] . However, there are very little data in the literature regarding the expression of these factors in melanomas confined to the iris and ciliary body [19,20] .…”

“…In addition, capillary elongation, lumen formation and extracellular matrix remodeling all require extensive proteolytic activity. Although many studies have addressed VEGF-A and MMP-9 expressions and EMPs in posterior uveal melanoma, very few have assessed them in iris and ciliary body melanomas [6,[12][13][14][15][16][17][18][19][20] .…”

Clinicopathological characteristics of vascular endothelial growth factor expression in uveal melanoma: A meta-analysis

“…Stitt et al (12) investigated the expression of VEGF mRNA, VEGF protein and its receptor in retinoblastoma or UM and reported a strongly positive VEGF expression in the tumor; the VEGF expression rate was higher compared to that in the uninvolved normal retina, choroid and iris. Sheidow et al (13) reported that 37% (16/43) of the patients with choroidal melanoma developed distant metastases within the 10-year follow-up, but did not confirm the association of VEGF expression with distant metastasis, although the expression of VEGF in the choroidal melanoma cells was strongly positive (94% positivity rate).…”