Conjunctival melanomas comprise 5% of all ocular melanomas
1 and show an increase in incidence. The majority of these melanomas is derived from primary-acquired melanosis (55%), while 25% arises de novo, and a minority of the conjunctival melanomas derives from nevi.
2 Conjunctival melanoma is associated with morbidity due to the frequent recurrences, with a 10-year mortality rate due to metastasis up to 30% to 39% in 10 years.
2,3 Once metastasized, there are only limited treatment options. This emphasizes the need for identification of biomarkers for early detection, prediction, and as potential treatment targets of lesions with more aggressive behavior. Many attempts have been made to predict the metastatic behavior of a conjunctival melanocytic lesion searching for prognostic parameters, including clinical and histopathologic parameters
4 and molecular changes, such as BRAF and TERT promoter mutations.
5 Nevertheless, the exact mechanism of metastasis has not been elucidated yet. Chemokines are thought to be involved in tumor proliferation, invasion, and angioinvasiveness,
6–8 and to play an important role in the metastatic process in different types of cancer,
9 including cutaneous and uveal melanoma.
9–12 Furthermore, chemokines play a role in inflammatory responses,
13,14 which might be involved in tumor progression.
14,15 Chemokine receptors are cytokine receptor-like G-linked proteins on the cell surface and are classified into four different groups, depending on the position of the cysteine residues.
10,11,14 It is suspected that tumor cells that express specific chemokine receptors tend to migrate toward the specific organ that produces the complementary ligand.
7,10,14,16,17 In this metastatic process, a role of a chemokine gradient is suggested
6,18 as well as an interaction between different chemokines and their receptors, matrix metalloproteinases, VEGF, and EGFR.
7 In melanocytic tumors, CXCR4, with its ligand CXCL12 (also known as stromal cell-derived factor 1 [SDF-1]
7,17), CCR7 with ligands CCL19 and CCL21,
9,18 and CCR10 with ligand CCL27 are thought to play a role in the metastatic spread.
18 So far little is known regarding chemokine receptor expression in conjunctival melanoma.
3