Inflammatory cytokines in eyes with uveal melanoma and relation with macrophage infiltration.
OBJECTIVE
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.
Departments of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
Long V
LV
Ly
Inge H G
IH
Bronkhorst
Els
E
van Beelen
Johannes
J
Vrolijk
Andrew W
AW
Taylor
Mieke
M
Versluis
Gregorius P M
GP
Luyten
Martine J
MJ
Jager
D000368:Aged; D001082:Aqueous Humor / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D015353:Eye Enucleation; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000502:physiology*; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008875:Middle Aged; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
D039481:CD11b Antigen; D017252:CD3 Complex; D016207:Cytokines; C509295:ITGAM protein, human