Vascular endothelial growth factor C mRNA expression correlates with stage of progression in patients with melanoma.

Vascular endothelial growth factor (VEGF)-C promotes the ingrowth and invasion of lymphatics in many different tumor types, including melanoma. To determine whether expression of VEGF-C correlates with stage of progression, we measured VEGF-C mRNA levels in melanomas representing different stages of progression and from the vertical and horizontal growth-phase of individual primary melanomas. Total RNA was extracted from human melanoma specimens taken from operative specimens and subjected to quantitative real-time PCR. VEGF-C levels were determined for 54 melanoma samples, including primary melanomas (n=15), local recurrences (n=6), regional dermal metastases (n=11), nodal metastases (n=12), and distant metastases (n=10). As a surrogate for lymphatic density, we also measured the expression of the lymphatic endothelial marker LYVE-1 and correlated its expression with previously measured VEGF-C levels. Vertical growth phase melanomas expressed significantly higher levels of VEGF-C than horizontal growth phase melanomas. Nodal metastases expressed the highest level of VEGF-C, followed by regional dermal metastases. Primary and local recurrences expressed a relatively low level of VEGF-C, as did negative lymph nodes and distant metastases. In addition, VEGF-C expression correlated well with LYVE-1 expression (r=0.611; P<0.0001). These data suggest that high levels of VEGF-C may be important in regional lymphatic disease in melanoma and that VEGF-C and LYVE-1 levels may identify tumors with a high risk for nodal metastases, for which antilymphangiogenic therapy may be more effective.