Tumor-infiltrating macrophages (CD68(+) cells) and prognosis in malignant uveal melanoma

Invest Ophthalmol Vis Sci. 2001 Jun;42(7):1414-21.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal
  • Antigens, CD / analysis*
  • Antigens, Differentiation, Myelomonocytic / analysis*
  • Cell Count
  • Cell Movement*
  • Cohort Studies
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Macrophages / immunology
  • Macrophages / pathology*
  • Male
  • Melanoma / blood supply
  • Melanoma / diagnosis*
  • Melanoma / immunology
  • Melanoma / mortality
  • Multivariate Analysis
  • Neovascularization, Pathologic / pathology
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Uveal Neoplasms / blood supply
  • Uveal Neoplasms / diagnosis*
  • Uveal Neoplasms / immunology
  • Uveal Neoplasms / mortality

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human