Detection of M2-macrophages in uveal melanoma and relation with survival

Invest Ophthalmol Vis Sci. 2011 Feb 3;52(2):643-50. doi: 10.1167/iovs.10-5979.

Abstract

Purpose: The presence of a high number of infiltrating macrophages in uveal melanoma is associated with a bad prognosis. However, there are several known types of macrophages, of which the M2 is considered to be proangiogenic and tumor-promoting. This study was conducted to determine whether the tumor-infiltrating macrophages in uveal melanoma are of this M2 subtype.

Methods: Macrophages were identified in sections from 43 uveal melanomas by immunofluorescence histochemistry, using monoclonal antibodies directed against CD68 and CD163. The immunopositive cell density was measured visually and with a confocal microscope and calculated per square millimeter. Results were compared with clinical and tumor characteristics.

Results: Infiltrating macrophages in uveal melanoma were predominantly CD68(+)CD163(+), thus of the M2 phenotype. The density of CD68(+), CD163(+), and CD68(+)CD163(+) cells was significantly increased in uveal melanomas with monosomy 3 compared with cases with disomy of chromosome 3 and was associated with ciliary body involvement. High CD68(+)CD163(+) staining was associated with an increased microvascular density. Survival was significantly better among patients with low CD68(+) and CD68(+)CD163(+) staining.

Conclusion: The main type of macrophage present in uveal melanoma was the M2 type. Tumors with monosomy of chromosome 3 contained a higher number of M2-macrophages than tumors with disomy of chromosome 3. Infiltration of M2-type macrophages gives a worse prognosis for survival. As M2-type macrophages are proangiogenic, a high density of these cells may contribute to the previously noticed positive association between the density of CD68(+) macrophages and blood vessels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism*
  • Antigens, Differentiation, Myelomonocytic / metabolism*
  • Cell Count
  • Cell Movement
  • Chromosomes, Human, Pair 3 / genetics
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Immunophenotyping
  • Macrophages / metabolism
  • Macrophages / pathology*
  • Male
  • Melanoma / diagnosis*
  • Melanoma / genetics
  • Melanoma / mortality
  • Microscopy, Confocal
  • Middle Aged
  • Monosomy / genetics
  • Phenotype
  • Prognosis
  • Receptors, Cell Surface / metabolism*
  • Survival Rate
  • Uniparental Disomy / genetics
  • Uveal Neoplasms / diagnosis*
  • Uveal Neoplasms / genetics
  • Uveal Neoplasms / mortality

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • CD68 antigen, human
  • Receptors, Cell Surface