Microvascular density in predicting survival of patients with choroidal and ciliary body melanoma

PURPOSE. Although malignant uveal melanoma disseminates predominantly hemat ogenously be cause of the absence of intraocular lymphatics, consensus abou t prognostic impact of microvascular density (MVD) has not been reached. Th is 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 enuclea ted because of choroidal or ciliary body melanoma from 1972 through 1981 wa s conducted. MVD was determined by counting tumor vessels in a masked fashi on from areas of highest vessel density after immunostaining for CD34 epito pe, factor VIII-related antigen (FVIII-RAg), and cu-smooth muscle actin (SM A). Kaplan-Meier and Cox regression analyses of survival were performed. Th e association between MVD and tumor size and location, cell type, and micro vascular 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 mm(2) (median, 40) and its association with presence o f microvascular loops and networks (P = 0.0006), epithelioid cells (P = 0.0 28), and largest basal tumor diameter(P = 0.0029) was statistically signifi cant. The 10-year melanoma-specific mortality increased with MVD (0.09, 0.2 9, 0.59, and 0.64, according to quartiles; P < 0.0001), as did all-cause mo rtality (P = 0.0022). Equivalent results were obtained with immunostaining for FVIII-RAg- whereas MVD obtained with antibodies to SMA was not associat ed 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, 103-1.20) for lar gest basal diameter, 1.23 (95% CI, 1.06-1.43) for square root-transformed M VD. and 151 (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 microvascula r patterns contribute independently to prognosis in uveal melanoma in:addit ion to cell type and size of the tumor.