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


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.
Clarijs
Ruud
R
Department of Pathology, University Medical Centre, Nijmegen, The Netherlands. r.clarijs@pathol.umcn.nl
Schalkwijk
Lia
L
Ruiter
Dirk J
DJ
de Waal
Robert M W
RM
D017209:Apoptosis; D002452:Cell Count; D002465:Cell Movement / Q000502:physiology*; D016207:Cytokines / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D008545:Melanoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D016601:RNA-Binding Proteins / Q000378:metabolism*; D014604:Uveal Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042582:Vascular Endothelial Growth Factor C; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D016207:Cytokines; D016228:Endothelial Growth Factors; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; D019010:Vascular Cell Adhesion Molecule-1; D042582:Vascular Endothelial Growth Factor C; C077219:small inducible cytokine subfamily E, member 1; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D040301:Vascular Endothelial Growth Factor Receptor-2