Angiogenesis and vascular growth factor receptor expression in malignant melanoma

The growth and metastases of many solid tumors are dependent on the recruit ment of new blood vessels. Tumor angiogenesis is most likely initiated by p aracrine release of growth factors that bind to their corresponding endothe lial cell surface receptors. To determine whether angiogenesis and growth f actor receptor expression are consistent findings in malignant melanoma, pr imary human melanomas were examined for mRNA expression of receptors for fi broblast growth factors (FGFR-1, FGFR-2), vascular endothelial growth facto r (VEGFR-1, VEGFR-2), and the receptors Tie1 and Tie2. Charts were reviewed and archival formalin-fixed, paraffin-embedded primary tumors were obtaine d from patients with thin (<1 mm; n = 10), intermediate (1 to 4 mm; n = 10) , or thick malignant melanoma (>4 mm; n = 8). Also examined was whether mel anoma cell lines could induce endothelial growth factor receptor synthesis by metabolic labeling. It was found that tumor vascularity did not correlat e with clinical stage, melanoma thickness, or clinical outcome. It was also found that melanoma cell lines were not capable of directly regulating end othelial cell synthesis of growth factor receptors. However, expression of Tiel and VEGFR-2 mRNA by the tumor vasculature in select stage IA-IIB patie nts, and FGFR-1 mRNA expression by the tumor cells in the same clinical sta ges was found. The expression of these growth factor receptors did not corr elate with clinical outcome. These data suggest that angiogenesis is not a prominent characteristic of primary malignant melanoma lesions and that the endothelial cell expression of Tiel and VEGFR-2 in vivo is probably not di rectly induced by the tumor.