Tumor-infiltrating macrophages (CD68(+) cells) and prognosis in malignant uveal melanoma.
OBJECTIVE
To investigate the hypothesis that tumor-infiltrating macrophages contribute to prognosis of uveal melanoma and to study their association with tumor characteristics, especially microvessels.


METHODS
This was a retrospective, population-based cohort study of 167 consecutive patients who had had an eye with choroidal and ciliary body melanoma removed between 1972 and 1981. Macrophages were identified with mAb PG-M1 to the CD68 epitope, and their number and morphologic type were recorded. Kaplan-Meier and Cox regression analyses of melanoma-specific survival were performed.


RESULTS
CD68-positive macrophages could be assessed in 139 (83%) of the 167 melanomas. Their number was moderate to high in 115 (83%) of the 139 tumors, and their morphology ranged from dendritic to round. A high number of macrophages was associated with presence of epithelioid cells (P = 0.025), heavy pigmentation (P = 0.001), and high microvascular density (P = 0.001). The 10-year melanoma-specific mortality rate increased with higher numbers of macrophages (0.10 for low versus 0.57 for high numbers, P = 0.0012). The morphologic type of infiltrating macrophages was not associated with mortality. The number of macrophages was modeled by stratification, which significantly improved a Cox regression model (P < 0.001). Adjusting for the other independent indicators of metastatic death 10-year melanoma-specific mortality was 0.17 for low versus 0.45 for high numbers of macrophages.


CONCLUSIONS
The number of tumor-infiltrating CD68-positive macrophages contributes to prognosis and associates with cell type and microvascular density, which merits a further analysis of the biological role of these cells in uveal melanoma.
Mäkitie
T
T
Ocular Oncology Service and Ophthalmic Pathology Laboratory, Department of Ophthalmology, Helsinki University Central Hospital, Finland. teemu.makitie@hus.fi
Summanen
P
P
Tarkkanen
A
A
Kivelä
T
T
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000032:analysis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis*; D002452:Cell Count; D002465:Cell Movement; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000276:immunology / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D015999:Multivariate Analysis; D009389:Neovascularization, Pathologic / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D014604:Uveal Neoplasms / Q000098:blood supply / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D000097382:CD68 Molecule
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C067980:CD68 antigen, human; D000097382:CD68 Molecule