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

Clin Cancer Res. 2003 Dec 1;9(16 Pt 1):5962-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Disease Progression
  • Glycoproteins / metabolism
  • Humans
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Staging
  • Neovascularization, Pathologic / metabolism
  • RNA, Messenger / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Vascular Endothelial Growth Factor C / genetics*
  • Vascular Endothelial Growth Factor C / metabolism
  • Vesicular Transport Proteins


  • Glycoproteins
  • LYVE1 protein, human
  • RNA, Messenger
  • RNA, Neoplasm
  • Vascular Endothelial Growth Factor C
  • Vesicular Transport Proteins