Microvessel density and VEGF, HIF-1alpha expression in primary oral melanoma: correlation with prognosis.

OBJECTIVE: To understand the role of angiogenesis and hypoxia in cancer progression of primary oral melanoma (POM). MATERIALS AND METHODS: Sixteen malignant primary melanomas were immunostained with markers CD34, VEGF and HIF-1alpha. Stained cells were counted in the invasive front and inside the tumour, and the differences were compared and correlated with histological parameters and disease-specific survival of the patients. RESULTS: Tumour invasive front showed increased MVD and increased vessel VEGF and HIF-1alpha expression compared with the intratumoural compartment. No such differences were seen in tumoural melanocytes of the two compartments. Positive correlations were observed between CD34 and VEGF, CD34 and HIF-1alpha and VEGF and HIF-1alpha expression in invasive front vessels. CD34 expression was statistically correlated with the level of infiltration. A significant trend to worse disease-free survival was also determined with increased invasive front vessel expression of CD34, VEGF and HIF-1alpha. CONCLUSIONS: Our data highlight the importance of the invasive margin in POM biology. The high angiogenic activity and endothelial VEGF and HIF-1alpha expression in invasive front vessels have a significant impact on patient survival and future agents targeted against VEGF pathway may represent a novel and effective therapeutic opportunity. Larger studies are needed to further address our findings.