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Vascular Endothelial Growth Factor C mRNA Expression Correlates with Stage of Progression in Patients with Melanoma

Division of Surgical Oncology, UMDNJ-Robert Wood Johnson Medical School, The Cancer Institute of New Jersey, New Brunswick, New Jersey

Purpose: 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.

Experimental Design: 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.

Results: 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).

Conclusions: 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.

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