Microvascular density in predicting survival of patients with choroidal and ciliary body melanoma.
OBJECTIVE
Although malignant uveal melanoma disseminates predominantly hematogenously because of the absence of intraocular lymphatics, consensus about prognostic impact of microvascular density (MVD) has not been reached. This study was undertaken to investigate whether MVD, microvascular patterns, or both determine prognosis of uveal melanoma.


METHODS
A population-based retrospective cohort study of melanoma-specific and all-cause mortality of 167 consecutive patients who had an eye enucleated because of choroidal or ciliary body melanoma from 1972 through 1981 was conducted. MVD was determined by counting tumor vessels in a masked fashion from areas of highest vessel density after immunostaining for CD34 epitope, factor VIII-related antigen (FVIII-RAg), and alpha-smooth muscle actin (SMA). Kaplan-Meier and Cox regression analyses of survival were performed. The association between MVD and tumor size and location, cell type, and microvascular patterns was assessed.


RESULTS
MVD could be determined from 134 of 167 melanomas (80%). Based on globally highest count obtained with antibodies to CD34, MVD ranged from 5 to 121 vessels/0.313 mm2 (median, 40) and its association with presence of microvascular loops and networks (P = 0.0006), epithelioid cells (P = 0.028), and largest basal tumor diameter (P = 0.0029) was statistically significant. The 10-year melanoma-specific mortality increased with MVD (0.09, 0.29, 0.59, and 0.64, according to quartiles; P < 0.0001), as did all-cause mortality (P = 0.0022). Equivalent results were obtained with immunostaining for FVIII-RAg, whereas MVD obtained with antibodies to SMA was not associated with prognosis. Cox regression showed a hazard ratio of 2.45 (95% CI, 1.43-4.18) for presence of epithelioid cells, 1.11 (95% CI, 1.03-1.20) for largest basal diameter, 1.23 (95% CI, 1.06-1.43) for square root-transformed MVD, and 1.51 (95% CI, 1.09-2.10) for presence of loops and networks, all of which independently contributed to prognosis.


CONCLUSIONS
The findings support the theory that both MVD and microvascular patterns contribute independently to prognosis in uveal melanoma in addition to cell type and size of the tumor.
Mäkitie
T
T
Department of Ophthalmology, Helsinki University Central Hospital, Finland. teemu.makitie@huch.fi
Summanen
P
P
Tarkkanen
A
A
Kivelä
T
T
D000199:Actins / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D002830:Choroid Neoplasms / Q000098:blood supply* / Q000175:diagnosis / Q000378:metabolism; D002924:Ciliary Body / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008545:Melanoma / Q000098:blood supply* / Q000175:diagnosis / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012189:Retrospective Studies; D014604:Uveal Neoplasms / Q000098:blood supply* / Q000175:diagnosis / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
D000199:Actins; D018952:Antigens, CD34; D014841:von Willebrand Factor