Lymphangiogenic and Chemotactic Factors in Conjunctival Melanoma

Abstract

The aim of this study was to evaluate expression patterns of known lymphangiogenic growth factors and chemokines in conjunctival melanoma, and to describe patterns of lymphatic vessel growth in these tumors. This was a retrospective chart review comprising 5 participants (6 tumor specimens) and the main outcome measures were expression of growth factors, chemokines, and their receptors known to be important in tumor lymphangiogenesis as well as patterns of lymphatic vessel growth on immunohistochemical sections. Tumor cells in all specimens expressed lymphangiogenic growth factors VEGFC, VEGFD, and their receptor VEGFR3. Chemotactic factors CXCL12 and CCL21 and their receptors, CXCR4 and CCL21, were also expressed in tumor cells and lymphatic endothelial cells. Staining was most intense for these proteins at the invasive tumor edge, suggesting increased lymphangiogenic activity at this location. In addition, lymphatic vessels clustered near the invasive edge of the tumors. VEGFC, VEGFD, and VEGR3 are diffusely expressed by conjunctival melanoma cells, most intensely at the invasive tumor edge. CXCL12, CXCR4, CCL21, and CCR7 were also most intensely expressed at the invasive edge, where the highest density of lymphatic vessels was also observed. These expression patterns suggest that these mediators of tumor-associated lymphangiogenesis warrant further investigation as potential therapeutic targets in conjunctival melanoma.