Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Tumour infiltrating macrophages, microvessels, and prognosis in malignant uveal melanoma

T Kivelä MD 1, T Mäkitie MD 2, P Summanen MD 1, A Tarkkanen MD 2

1 Ocular Oncology Service and, 2 Ophthalmic Pathology Laboratory, Dept Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland,

AIMS: To investigate the association between macrophages, microvessels and survival in uveal melanoma. METHODS: A consecutive series of 167 patients with a choroidal and ciliary body melanoma enucleated in 1972-81 was analyzed. Infiltrating macrophages were identified with mAb PG-M1 to CD68 epitope. The number and predominant type of macrophages was recorded semiquantitatively. Presence of microvascular loops and networks (MVLN) and microvascular density (MVD) were determined. Univariate Kaplan-Meier and multivariate Cox regression analysis were used to model survival. RESULTS: The number of macrophages was moderate to high in 83% (95% CI, 75-89) of uveal melanomas. High number of macrophages was associated with presence of epithelioid cells (P =.025), heavy tumour pigmentation (P =.001), and high microvascular density (P =.001). 10-year melanoma-specific mortality was 0.10 for low, 0.42 for moderate and 0.57 for high numbers of infiltrating macrophages (P = .003, Kaplan Meier). Their morphology ranged from predominantly dendritic to plump phagocytosing cells, a feature which was not associated with prognosis. Number of macrophages did not fulfill the proportional hazards assumption, and was treated as a stratification variable. Stratified Cox regression indicated that MVLN and MVD, cell type, and tumour size were independent predictors of metastatic death. CONCLUSIONS: Microvascular factors are strong predictors of metastatic death in uveal melanoma, which spreads purely hematogenously. Macrophages are a prominent stromal component in these tumours, and their number is associated with both tumour (cell type) and stromal (microvascular density) characteristics. Number of infiltrating macrophages must be controlled for in statistical modeling, and they might modify tumor progression.

KEY WORDS: angiogenesis, microvascular mimicry, monocytes, immune response, dendritic cells.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on prognostic markers.