EMAP-II expression is associated with macrophage accumulation in primary uveal melanoma

PURPOSE. Primary uveal melanoma may contain arcs, loops, and networks of periodic acid-Schiff (PAS)-positive patterns, along which numerous macrophages are present. Their recruitment into tumor tissue is mediated by chemotactic cytokines, for which vascular endothelial growth factor (VEGF)-C and endothelial monocyte-activating polypeptide (EMAP)-II are candidates. In this study, the extent of VEGF-C and EMAP-II immunoreaction was related to infiltration of macrophages. METHODS. Serial sections of 25 primary uveal melanoma lesions were analyzed by inummohistochemistry. RESULTS. The analysis showed no correlation of VEGF-C immunoreaction and localization of macrophages. However, accumulation of macrophages occurred at sites of EMAP-II expression, especially in areas containing nests of tumor cells, surrounded by arcs, loops, and network patterns. In tumors with a strong EMAP-II immunoreaction, the adhesion molecule intracellular adhesion molecule (ICAM)-1 was strongly expressed on endothelial cells. EMAP-II-positive endothelial cells did not express VEGF receptor-2. However, extensive release of von Willebrand factor was observed. Signs of apoptosis were found neither in tumor cells nor endothelial cells. CONCLUSIONS. In uveal melanoma, macrophages accumulate at sites of EMAP-II expression. Based on the results, it may be hypothesized that this process of chemotaxis is facilitated by EMAP-II- dependent expression of ICAM-1 on vascular endothelial cells and concomitantly leads to localized vascular damage, as indicated by release of von Willebrand factor.