Uveal melanomas express vascular endothelial growth factor and basic fibroblast growth factor and support endothelial cell growth

Boyd, S R; Tan, Dongfeng; Souza, L de; Neale, Michael H.; Myatt, Nyree; Alexander, Robert; Robb, Malcolm; Hungerford, J. L.; Cree, Ian A.

doi:10.1136/bjo.86.4.440

Cited by 57 publications

(45 citation statements)

References 46 publications

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“…Boyd et al [12] found VEGF-A protein expression in 54% of normal iris and ciliary body tissues. The authors suspected that either the normal ciliary body and iris may contribute to the production of VEGF-A or this may result from the anterior diffusion of VEGF-A from the tumor.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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Purpose: It was the aim of this study to assess the expression of vascular endothelial growth factor (VEGF)-A, matrix metalloproteinase (MMP)-9 and extravascular matrix patterns (EMPs) in iris and ciliary body melanomas and their correlations with histopathologic parameters. Methods: The study was conducted on 3 iris and 15 ciliary body melanomas. All tumors were subjected to immunohistochemical techniques for VEGF-A and MMP-9 expressions, the presence of EMPs was assessed, and routine paraffin sections were stained with hematoxylin-eosin. Cell type, tumor localization, degree of pigmentation, necrosis, mitotic index, lymphocytic infiltration and sclera invasion were analyzed using light microscopy. Results: The mean patient age at the time of treatment was 43 years (range 19–69, median 39.5); 10 (55.6%) patients were males and 8 (44.4%) females. Histopathological cell types were spindle cells in 55.6%, mixed cells in 16.7%, and epithelioid cell types in 27.8% of tumors. Positive reaction for VEGF-A and MMP-9 was present in 66.7 and 72.3% of the tumors, respectively. Microvascular loops and/or networks were seen in 33.4% of the tumors, with the remaining 66.7% of tumors displaying one or more of the other patterns. Metastatic disease developed in only 1 patient during follow-up. Tumor cell type, tumor size, mitotic rate, degree of pigmentation and EMPs were not correlated with metastasis. Conclusions: This study suggests that VEGF-A and MMP-9 were positive in the majority of iris and ciliary body melanomas. No correlation was found between VEGF-A and MMP-9 immunoreactivity and EMPs and occurrence of metastases in cases of anterior uveal melanoma.

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Section: Discussionmentioning

confidence: 99%

“…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] .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2006

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“…These risk factors may be indicative of eyes at high risk for CME that may be less responsive to anti-VEGF therapy prior to or following plaque radiotherapy. Furthermore, prior studies have demonstrated variable expression of VEGF and other growth factors amongst uveal melanoma cell lines [24]. Greater production of VEGF, or production of proexudative growth factors other than VEGF, by the individual tumors may also explain variable treatment response to high-dose anti-VEGF therapy in this study.…”

Section: Discussionmentioning

confidence: 64%

High-Dose (2.5 mg) Intravitreal Bevacizumab as Rescue Therapy for Persistent Postradiation Cystoid Macular Edema

et al. 2017

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Background/Aims: To investigate the efficacy of intravitreal high-dose (2.5 mg/0.1 mL) bevacizumab as rescue therapy for postradiation cystoid macular edema (CME) resistant to standard-dose (1.25 mg/0.05 mL) bevacizumab. Methods: Retrospective, interventional case series. Results: Fifteen eyes of 15 patients were included. Eyes were treated with a mean of 10 standard-dose (1.25 mg) bevacizumab injections but failed to show CME resolution. Following 3 monthly treatments of high-dose (2.5 mg) bevacizumab, mean central macular thickness (CMT) reduced significantly from 406 ± 100 to 360 ± 83 μm (p = 0.01) and mean logMAR visual acuity improved from 0.55 ± 0.17 (Snellen 20/71) to 0.48 ± 0.21 (Snellen 20/60, p = 0.07). At the final follow-up of 9 months, CMT was 395 ± 124 μm (p = 0.67) and visual acuity was 0.51 ± 0.23 (Snellen 20/65, p = 0.22). Five eyes (30%) had a >10% reduction in CMT at the final follow-up. In these eyes, the observed CMT reduction was statistically significant (p = 0.04) and logMAR visual acuity was significantly better (p ≤ 0.01) compared to the remainder of the cohort. Conclusions: Overall, the use of high-dose (2.5 mg) bevacizumab did not result in a sustained, significant improvement in CMT and visual acuity outcomes following incomplete response to standard-dose (1.25 mg) bevacizumab. However, a minority of eyes exhibited favorable response with significant CMT reduction.

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“…Furthermore, fibrovascular membranes in the trabecular area were found in all cases of increased IOP. Finally, tumour cells may produce vasoproliferative growth factors, inducing formation of fibrovascular membranes (Boyd et al 2002;Walker et al 2002;Abdel-Rahman et al 2005).…”

Section: Part Iii: Discussionmentioning

confidence: 99%

Primary and secondary tumours of the optic nerve, with emphasis on invasion by uveal malignant melanoma

Lindegaard

2007

Acta Ophthalmologica Scandinavica

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Tumours of the optic nerve may originate in the optic nerve itself (i.e. primary tumours) or in structures adjacent to the optic nerve (i.e. secondary tumours). Furthermore, leukaemic infiltration and tumour metastases from distant solid tumours are also found in the optic nerve (i.e. secondary tumours). Large surveys have described primary optic nerve tumours and their treatment modalities, whereas secondary tumours have received little attention. Most reported work-ups have been based on material from referral centres and specialized departments.The correlation between invasion of the optic nerve in uveal melanoma and the risk of death from the disease has not been fully elucidated. The impact on prognosis may be correlated with tumour cells left in the proximal nerve after enucleation. In addition, melanoma with secondary invasion of the optic nerve may represent a highly malignant invasive subcategory of uveal melanoma. Clinical factors that make the ophthalmologist aware of optic nerve invasion when investigating a uveal melanoma are most important.Melanomas that invade the optic nerve may histopathologically display different invasive patterns and represent different types of uveal melanoma. A subtype of uveal melanoma with a preponderance for neural invasion may exist. Such a subtype has been identified for cutaneous melanoma (desmoplastic ⁄ neurotropic).In order to investigate tumours of the optic nerve in a known population, we studied all optic nerve tumours that had been surgically removed in Denmark over a period of 25 years. Furthermore, in order to resolve questions about secondary invasion of the optic nerve in uveal melanoma, we investigated all eyes with uveal melanoma and optic nerve invasion enucleated in Denmark between 1942 and 2001 (n ¼ 157).Tumours of the optic nerve in children were dominated by optic glioma and invasion from retinoblastoma, whereas tumours in adults mainly comprised optic nerve sheath meningioma and invasion from uveal melanoma.Optic nerve invasion of uveal melanoma was found in one in 20 patients. Increased IOP and juxtapapillary location were associated with both pre-laminar ⁄ laminar and post-laminar invasion of the optic nerve. Furthermore, ageReuse of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. Acta Ophthalmologica Scandinavica 20071 over 70 years, vision reduced to light perception, non-visible fundus and large tumour size were associated with post-laminar invasion. Only patients with optic nerve invasion had metastases to the CNS, kidney and heart. Histopathological features associated with optic nerve invasion were focal retinal invasion, neovascularization of the chamber angle and scleral invasion. Furthermore, non-spindle cell type and rupture of the ILM were all associated with post-laminar invasion.The optic nerve was invaded in four different ways:(1) by tumour extension from the neuroretina through the lamina cribrosa; (2) by direct extension into the optic ...

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Uveal melanomas express vascular endothelial growth factor and basic fibroblast growth factor and support endothelial cell growth

Cited by 57 publications

References 46 publications

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

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

High-Dose (2.5 mg) Intravitreal Bevacizumab as Rescue Therapy for Persistent Postradiation Cystoid Macular Edema

Primary and secondary tumours of the optic nerve, with emphasis on invasion by uveal malignant melanoma

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