Inflammatory cytokines in eyes with uveal melanoma and relation with macrophage infiltration

Abstract

Purpose: The presence of an inflammatory phenotype, characterized by an increased expression of HLA antigens and an immunologic infiltrate, carries a bad prognosis in uveal melanoma. This study was conducted to determine whether the aqueous humor (AqH) from eyes with uveal melanoma contains inflammatory cytokines and whether their presence is associated with inflammation.

Methods: Immediately after enucleation, AqH was obtained from 37 eyes containing uveal melanoma. Samples were stored at -80°C until use. Fifteen different cytokines were measured with a multiplex bead array. Intratumoral macrophages were analyzed by immunohistochemistry and immunofluorescence staining. The presence of specific cytokines was compared with histopathologic, genetic, and clinical tumor characteristics, as well as patient survival.

Results: Several cytokines showed significantly higher expression in the AqH of uveal melanoma-containing eyes than in the AqH of eyes undergoing cataract surgery. MCP-3 was associated with the presence of CD68(+) macrophages. Correlations were found between some cytokine levels and a few known prognostic factors of uveal melanoma, but cytokine levels were not of predictive value for survival.

Conclusions: Uveal melanoma-containing eyes often carry increased levels of inflammation-related cytokines in their AqH. However, the presence of most specific cytokines was not related to the presence of macrophages, clinical or histopathologic parameters, or prognosis.

Figure 1.

Expression of 15 different cytokines in AqH of eyes with uveal melanoma and control eyes with cataract. For most cytokines, the concentration of the cytokine was significantly higher in eyes with uveal melanoma. Horizontal line: the mean in each group.

Figure 2.

Expression of the cytokine MCP-3 versus the three groups of CD68 IHC (A, horizontal line represents the mean) and correlation with CD68 IF (B) and CD68 and CD163 IF (C) staining. Significant associations or correlations were observed between both types of CD68 staining and MCP-3.