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I. H. Bronkhorst, L. V. Ly, E. S. Jordanova, H. Vrolijk, M. Versluis, M. J. Jager; Tumor-Promoting M2 Macrophages in Uveal Melanoma: Relevance for Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6456.
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The presence of high numbers of macrophages in uveal melanoma is associated with a bad prognosis. However, several types of macrophages are known to exist, of which one subtype, the so-called M2-macrophage, is considered to be pro-angiogenic and tumor-promoting. We determined the presence of these macrophages in uveal melanoma.
The percentage of M2 macrophages was identified in sections from 43 uveal melanomas using double immunofluorescence histochemistry, with monoclonal antibodies directed against CD163 and CD68. The staining area was measured manually by threshold and calculated using a Stacks software program. Findings were compared with clinical and tumor characteristics. Monosomy of chromosome 3 was determined on isolated nuclei and by karyotyping.
Infiltrating macrophages were predominantly CD163+CD68+, thus of the M2 phenotype. The density of CD68+, CD163+ and CD163CD68 double-positive cells was markedly increased in uveal melanoma with monosomy 3 compared to disomy 3 (p = 0.001, p = 0.039 and p = 0.007, respectively). Ciliary body involvement was associated with high staining (p = 0.019, p = 0.047 and p = 0.047, respectively) and the presence of epithelioid cell type correlated with high CD68+ staining (p = 0.024).
The main type of macrophage present in uveal melanoma was of the M2 type. Tumors with monosomy of chromosome 3 contained higher numbers of M2 macrophages than tumors with disomy of chromosome 3. As M2 type macrophages are pro-angiogenic, the high density of these cells may contribute to the increased vascular density that was previously noticed in tumors with increased numbers of CD68 macrophages (Makitie et al., 2001).
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