Expression of haematogenous and lymphogenous chemokine receptors and their ligands on uveal melanoma in association with liver metastasis

Purpose: Chemokine receptors and their ligands are involved in a number of cell processes, including normal cell trafficking as well as metastasis in cancer. During metastasis, they are thought to play a role in determining cancer cell distribution and target organs. The aim of this study was to examine the expression of the chemokine receptors CXCR4, CCR7 and CCR10 as well as their respective chemokine ligands (CXCL12, CCL19, CCL27) in human uveal melanomas. Methods: Seventy formalin-fixed paraffin-embedded uveal melanoma specimens from patients treated in 19961997 were examined using immunohistochemistry and evaluated using an immune reactive score (IRS). Results: The chemokine receptors CXCR4, CCR7 and CCR10 were primarily expressed in the cytoplasm of uveal melanoma cells, with CXCR4 (average IRS 8.2) and CCR7 (average IRS 5.7) showing the strongest expression, respectively. The chemokine ligand CCL19 demonstrated a moderate expression (average IRS 5.3), whereas the expression of receptor CCR10 (average IRS of 3.4), ligand CCL27 (average IRS 2.5) and ligand CXCL12 (average IRS 0.6) by uveal melanoma cells was low. A significant association between liver metastases and chemokine expression was found for CCR7 expression (p = 0.037) only. Comparison of liver metastasis and choroid uveal melanoma (35.3%, n = 12 of 34) versus ciliary body involvement (72.7%, n = 8 of 11) was significant (p = 0.030). Conclusion: Chemokine receptors are more strongly expressed on uveal melanoma cells than their ligands. Our results show new aspects of the metastatic process in uveal melanoma.