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


METHODS
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.
Goydos
James S
JS
Division of Surgical Oncology, UMDNJ-Robert Wood Johnson Medical School, The Cancer Institute of New Jersey, New Brunswick, New Jersey 08901, USA.
Gorski
David H
DH
D018450:Disease Progression; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics* / Q000378:metabolism; D033921:Vesicular Transport Proteins
D006023:Glycoproteins; C119248:LYVE1 protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D042582:Vascular Endothelial Growth Factor C; D033921:Vesicular Transport Proteins