Vascular Endothelial Growth Factor A in Eyes With Uveal Melanoma

Abstract

To determine the presence of vascular endothelial growth factor A (VEGF-A) in the aqueous humor of eyes with uveal melanoma and to identify its source. Methods: The VEGF-A concentrations were determined in aqueous humor samples obtained after enucleation from 74 eyes with untreated uveal melanoma and from 8 eyes with treated uveal melanoma. Patient survival and clinical and histopathological tumor variables were compared. In situ hybridization, Western blot analysis, and enzyme-linked immunosorbent assay were used to determine expression of VEGF-A in tumor tissue and in overlying retina. Results: Aqueous VEGF-A concentrations ranged from 18 to 826 pg/mL in 74 untreated eyes, while concentrations in 30 control eyes were significantly lower (median, 50.1 pg/mL) (PϽ.001). Concentrations in 8 treated eyes were much higher (median, 364 pg/mL). In situ hybridization on tissue sections and Western blot analysis and enzyme-linked immunosorbent assay on tissue extracts revealed VEGF-A in uveal melanoma tissue and in retinal tissue. Conclusions: Uveal melanoma is associated with increased concentrations of VEGF-A in aqueous humor. Aqueous VEGF-A concentration correlates with largest basal tumor diameter and with the tumor height. In eyes with uveal melanoma, tumor and retinal tissues are sources of VEGF-A.

Local environmental influences on uveal melanoma

“…In contrast, it was of interest that VEGF, a potent angiogenic stimulator, was not comparatively more highly expressed (Table 2), as studies have shown raised VEGF in the aqueous and vitreous from patients with uveal melanoma. 14,23 It is expected that the aqueous and vitreous contain a myriad array of other factors not tested for in this preliminary study, and the relatively low comparative expression of VEGF in this study may suggest that the aqueous and vitreous of patients with uveal melanoma show a dramatic rise in a large number of other potentially more influential regulators. Further studies comparing the levels of regulators found in the aqueous and vitreous from a larger series of uveal melanomas, with comparison of the levels seen in patients with other ocular conditions, such as those undergoing vitrectomy and cataract surgery, will be required to confirm this hypothesis.…”

Endodrainage, Tumor Photocoagulation, and Silicone Oil Tamponade for Primary Exudative Retinal Detachment due to Choroidal Melanoma Persisting after Proton Beam Therapy

“…In their study, Missotten et al [22 ]found significantly elevated aqueous VEGF levels in eyes with uveal melanoma irrespective of the treatment compared with controls and eyes with a retinal detachment alone. The current literature shows overall 5-year neovascular glaucoma rates of approximately 11-31% in modern proton-treated uveal melanoma patients with neovascular glaucoma, and this typically occurs in the first 3 years after treatment [23,24,25].…”

Angiogenesis in Uveal Melanoma

“…While the first studies on the application of drugs for treatment of radiation retinopathy are being reported [16] , using anti-angiogenesis drugs in the treatment of the primary tumour is still in the laboratory phase. It is known that uveal melanomas and uveal melanoma cell lines produce factors like VEGF and angiopoietin-1 and -2 [6,17] , which are known to stimulate vessel growth, an essential requirement for tumour enlargement. Inhibition of factors like VEGF may therefore contribute to inhibition of further tumour growth.…”