Intraocular activation of angiogenic and inflammatory pathways in uveal melanoma.

Abstract

PURPOSE:

To identify and quantify angiogenic and inflammatory cytokines in aqueous and vitreous humor in eyes with untreated uveal melanoma and to analyze clinicopathologic correlations.

METHODS:

Intraocular fluid samples of patients (uveal melanoma aqueous n = 21, vitreous n = 34) and controls (cataract aqueous n = 41, vitreomacular traction aqueous n = 35, vitreous n = 36) were taken intraoperatively and analyzed using Luminex xMAP suspension array technology. Beadlyte kits were used for detection of 28 different cytokines.

RESULTS:

Flt-3 ligand, interleukin (IL) 1α, IL-6, IL-8, interferon-γ inducible protein (IP)-10, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1α, platelet-derived growth factor AA, and vascular endothelial growth factor were significantly elevated in aqueous and vitreous of melanoma eyes when compared with controls. Eotaxin was significantly elevated in aqueous, and IL-7 and RANTES were significantly elevated in vitreous samples of melanoma eyes. Interferon-γ inducible protein 10, macrophage inflammatory protein 1α (aqueous and vitreous), Flt-3 ligand, IL-6, IL-8, and MCP-1 (vitreous) correlated with tumor dimensions. Further correlations were found between infiltration of Bruch membrane and Flt-3 ligand, MCP-1 (aqueous and vitreous), IL-8, interferon-γ inducible protein 10, macrophage inflammatory protein 1α, and platelet-derived growth factor AA (vitreous). Analyzing 16 paired aqueous and vitreous melanoma samples, Flt-3 ligand, IL-7, interferon-γ inducible protein 10, MCP-1, and platelet-derived growth factor AA were significantly elevated in vitreous, and IL-1α and vascular endothelial growth factor in aqueous samples.

CONCLUSION:

A range of significantly elevated angiogenic, inflammatory, and chemotactic cytokines in eyes with uveal melanoma supports the link between inflammation and tumorigenesis.

• Authors: Roman Dunavoelgyi, Marion Funk, Stefan Sacu, Michael Georgopoulos, Gerhard Zlabinger, Martin Zehetmayer, Ursula Schmidt-Erfurth
• Journal: Retina (Philadelphia, Pa.) (Retina) Vol. 32 Issue 7 Pg. 1373-84 (Jul 2012) ISSN: 1539-2864 [Electronic] United States
• PMID: 22418780 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inducing Agents
• Cytokines

Topics

• Aged
• Angiogenesis Inducing Agents (metabolism)
• Aqueous Humor (metabolism)
• Chromosomes, Human, Pair 3 (genetics)
• Cytokines (metabolism)
• Eye Enucleation
• Female
• Humans
• Male
• Melanoma (genetics, metabolism, pathology, radiotherapy)
• Monosomy (genetics)
• Prospective Studies
• Uveal Neoplasms (genetics, metabolism, pathology, radiotherapy)
• Vitreous Body (metabolism)