Article

Clinical significance of vascular endothelial growth factor-C (VEGF-C) in breast cancer.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Breast Cancer Research and Treatment (Impact Factor: 4.47). 04/2001; 66(2):159-64. DOI: 10.1023/A:1010692132669
Source: PubMed

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.

0 Bookmarks
 · 
58 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cervical lymph node metastasis in oral squamous cell carcinoma (OSCC) is recognized as a poor prognostic factor, although its mechanism remains unclear. Recently, cyclo-oxygenase-2 (COX-2) level has been found to correlate highly with vascular endothelial growth factor C (VEGF-C) and lymph node metastasis, as in other solid tumors. However, there has been no report of this correlation in OSCC. Therefore, the aim of this study was to investigate whether COX-2 immunohistochemical expression in OSCC was associated with VEGF-C expression, histopathologic parameters, and lymph node metastasis. Lymphatic vessel density, VEGF-C, and COX-2 immunohistochemical expression were examined pathologically in 60 specimens of invasive OSCC. Relations of histopathologic parameters to lymph node metastasis were analyzed. Expression levels of VEGF-C and COX-2 and lymphatic vessel density in the lymph node metastatic group were significantly higher than in the nonmetastatic group (P < .01). A significant correlation was found between the expression levels of VEGF-C and COX-2 (r = 0.512; P < .001). COX-2 expression was significantly related to lymph node metastasis (P = .004) and VEGF-C expression (P = .005). Univariate analysis showed that survival time was impaired by higher COX-2 and VEGF-C expression levels. Multivariate survival analysis showed that COX-2 expression was an independent prognostic factor. This study showed that VEGF-C expression was upregulated by COX-2 in OSCC. High VEGF-C expression appears to promote peritumoral lymphangiogenesis. These data indicated that lymph node metastasis is promoted by COX-2 and VEGF-C in OSCC.
    Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 06/2013; · 1.58 Impact Factor
  • Source
    [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. · 2.09 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; · 2.52 Impact Factor