Drs. Yukuan Feng and Wei Wang contributed equally to this work.
Expression of VEGF-C and VEGF-D as Significant Markers for Assessment of Lymphangiogenesis and Lymph Node Metastasis in Non-Small Cell Lung Cancer
Article first published online: 11 MAR 2010
Copyright © 2010 Wiley-Liss, Inc.
The Anatomical Record
Volume 293, Issue 5, pages 802–812, May 2010
How to Cite
Feng, Y., Wang, W., Hu, J., Ma, J., Zhang, Y. and Zhang, J. (2010), Expression of VEGF-C and VEGF-D as Significant Markers for Assessment of Lymphangiogenesis and Lymph Node Metastasis in Non-Small Cell Lung Cancer. Anat Rec, 293: 802–812. doi: 10.1002/ar.21096
- Issue published online: 23 APR 2010
- Article first published online: 11 MAR 2010
- Manuscript Accepted: 23 NOV 2009
- Manuscript Received: 11 DEC 2008
- National Natural Science Foundation of China. Grant Number: 36072420
- Department of Science and Technology of Heilongjiang Province of China. Grant Number: QC07C80
- Department of Education of Heilongjiang Province of China. Grant Numbers: 1151G058, YSSCX2009-219HLJ
- Department of Public Health of Heilongjiang Province of China. Grant Number: 2007-004
- lymph nodes;
- neoplasm metastasis;
- non-small cell lung carcinoma
Vascular endothelial growth factor (VEGF)-C and VEGF-D induce lymphangiogenesis through activation of VEGF receptor 3 (VEGFR-3) and have been implicated in tumor spread to the lymphatic system. Lymph node dissemination critically determines clinical outcome and therapeutic options of patients with non-small cell lung cancer (NSCLC). However, the relationship of VEGF-C, VEGF-D, and lymph node metastasis in cancers, including NSCLC, is still controversial. To evaluate the relationship between lymphangiogenesis and lymph node metastasis, the expression of VEGF-C and VEGF-D in NSCLC tumors were detected by immunohistochemistry and quantitative real-time polymerase chain reaction (QRT-PCR). QRT-PCR revealed that in marginal region VEGF-C and VEGF-D mRNA was significantly higher than in tumor center, and VEGF-D mRNA was also higher than that in peritumoral lung tissue. Immunohistochemically, we observed the same heterogeneous expression of VEGF-C and VEGF-D proteins. The group with high expression of VEGF-C and VEGF-D in marginal region had a higher incidence of lymph node metastasis compared with the group with low expression. Furthermore, the group with high expression of VEGF-D in marginal region had a higher incidence of lymphatic invasion. The group with high peritumoral lymphatic vessel density (LVD) had higher expression of VEGF-C and VEGF-D mRNA compared with the group with low peritumoral LVD. Our studies suggested that the expression of VEGF-C and VEGF-D at invasive edge was significantly associated with lymph node metastasis or lymphatic invasion in patients with NSCLC and may be involved in regulation of lymphangiogenesis and lymph node metastasis in NSCLC. Anat Rec, 2010. © 2010 Wiley-Liss, Inc.