Clinical significance of vascular endothelial growth factor-C (VEGF-C) in breast cancer.
ABSTRACT Vascular endothelial growth factor-C (VEGF-C) is a specific ligand which induces lymphangiogenesis. We examined the expression of VEGF-C protein to determine its role in the progression of breast cancer. Immunohistochemical analysis revealed that VEGF-C was overexpressed in 39 of 98 breast cancer specimens (39.8%) but not in adjacent normal mammary glands. The expression of VEGF-C showed a significant correlation with lymphatic vessel invasion (p = 0.0004). It is noteworthy that the 5-year disease free survival rate of the VEGF-C positive group was significantly poorer than that of negative group (p = 0.0356). We suggest that as expression of VEGF-C is not implicated in lymphatic spread, it may prove to be a promising marker to predict the recurrence of breast cancer.
- SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: Metastatic spread of tumor through lymphatic vasculature is an important adverse prognostic factor in a variety of human cancer and tumor lymphangiogenesis requires the interplay of several growth factors. Platelet-derived growth factor (PDGF)-BB and vascular endothelial growth factor (VEGF)-C are two important molecules involving in tumor metastasis and lymphangiogenesis. Therefore, the aim of this study was to investigate the coexpression of PDGF-BB and VEGF-C in primary human non-small cell lung cancer (NSCLC) and its association with lymphangiogenesis.Diagnostic Pathology 06/2014; 9(1):128. · 2.41 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Recent evidence suggests that vascular endothelial growth factor-C (VEGF-C)- dependent tumour production promotes lymphangiogenesis, while membrane-type matrix 1 metalloproteinase (MT1-MMP) is involved in the critical steps leading to carcinogenesis. However, the role of MT1-MMP in lymphangiogenesis and lymphatic metastasis remains poorly understood. In the present study, we investigated the relationship between MT1-MMP and VEGF-C in human breast cancer and correlated MT1-MMP and VEGF-C expression with lymphangiogenesis and prognosis. MT1-MMP and VEGF-C levels were compared in five breast carcinoma cell lines. We used a membrane invasion assay to assess the effect of MT1-MMP and VEGF-C expression, as well as anti-MT1-MMP and VEGF-C antibodies, on cancer cell invasion. We further assessed MT1-MMP and VEGF-C immunoreactivity and lymph vessels in a cohort of human breast cancer specimens (n = 106) and associated MT1-MMP and VEGF-C expression with clinicopathological parameters, such as lymphatic vessel density (LVD), and patient prognosis. MT1-MMP and VEGF-C expression differed among the five breast cancer cell lines and MT1-MMP and VEGF-C expression were correlated with tumour cell invasion. VEGF-C mRNA expression levels and invasive activity of MDA-MB-231 cells was inhibited by an anti-MT1-MMP antibody in a concentration-dependent manner. A significant correlation was found between the expression of MT1-MMP and VEGF-C in breast cancer patient samples and elevated MT1-MMP and VEGF-C expression was associated with higher LVD, lymph node metastasis, cancer stage, and a decline in overall survival rates. Our data demonstrate that MT1-MMP expression is closely correlated with VEGF-C expression, and that MT1-MMP promotes lymphangiogenesis by up-regulating VEGF-C expression in human breast cancer. Thus, elevated MT1-MMP may serve as a significant prognostic factor in breast cancer.Cancer Cell International 10/2013; 13(1):98. · 1.99 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Vascular endothelial growth factor-C (VEGF-C) is considered as a prime mediator of lymphangiogenesis and has been implicated in carcinogenesis and metastasis. Various studies examined the relationship between VEGF-C protein overexpression with the clinical outcome in patients with breast cancer but yielded conflicting results. Electronic databases updated to April 2013 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between VEGF-C overexpression and survival of patients with breast cancer. Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 11 studies (n = 1,357 patients) that evaluated the correlation between VEGF-C overexpression detected by immunohistochemistry and survival in patients with breast cancer. Combined hazard ratios suggested that VEGF-C overexpression was not associated with poor prognosis of disease-free survival (HR [hazard ratio] = 0.80, 95 % CI [confidence interval]: 0.51-1.09), overall survival (OS) (HR = 1.08, 95 % CI: 0.37-1.78) in patients with breast cancer. In the stratified analysis by patient source, significantly risks were not found among Asians or non-Asians. No significant heterogeneity was observed among all studies. VEGF-C overexpression was not associated with poor disease-free survival or overall survival in breast cancer.Tumor Biology 09/2013; · 2.84 Impact Factor