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


CONCLUSIONS
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.
Bronkhorst
Inge H G
IH
Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
Ly
Long V
LV
Jordanova
Ekaterina S
ES
Vrolijk
Johannes
J
Versluis
Mieke
M
Luyten
Gregorius P M
GP
Jager
Martine J
MJ
D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D002452:Cell Count; D002465:Cell Movement; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D016130:Immunophenotyping; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D018613:Microscopy, Confocal; D008875:Middle Aged; D009006:Monosomy / Q000235:genetics; D010641:Phenotype; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015996:Survival Rate; D024182:Uniparental Disomy / Q000235:genetics; D014604:Uveal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D000098902:CD163 Antigen; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule