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BMC Cancer  2008 

Coexpression of VEGF-C and COX-2 and its association with lymphangiogenesis in human breast cancer

DOI: 10.1186/1471-2407-8-4

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Tissue samples of primary tumors from 70 patients undergoing intentionally curative surgical resections for breast cancer were immunohistochemically examined for VEGF-C, COX-2, and D2-40 expressions. The association between COX-2 and VEGF-C expressions and clinicopathological parameters as well as prognosis were analysised. To demonstrate the presence of proliferating lymphatic endothelial cells, 10 random cases with high LVD counts were selected for D2-40/Ki-67 double immunostaining.A significant correlation was found between the expression of VEGF-C and COX-2 (r = 0.529, P < 0.001), and both elevated VEGF-C expression and elevated COX-2 expression were associated with higher lymph vessel density (LVD), lymph node metastasis and D2-40 positive lymphatic invasion (LVI) as well as worse disease free survival (DFS) and overall survival (OS) in a univariate analysis. In the double immunostain for the lymph vessel marker D2-40 and the proliferation marker Ki-67, the results confirmed Ki-67-positive nuclei in a proportion of lymph vessel endothelial cells.There is indeed lymphangiogenesis in breast cancer, the most compelling evidence being the presence of proliferating lymphatic endothelial cells. VEGF-C and COX-2 are coexpressed and significantly associated with lymphangiogenesis and prognosis in invasive breast cancer. Suggesting COX-2 may up-regulate VEGF-C expression and thus promote lymph node metastasis via lymphangiogenesis pathway in human breast cancer.The lymphatic vasculature is an important route for the metastatic spread of human cancer. And the presence of tumour foci in lymph nodes is the most important adverse prognostic factor in a variety of human cancers. Recently, lymphangiogenesis, the formation of new lymphatic vessels, has become a new research frontier in tumor metastasis since the discovery of the two major lymphatic vessel growth factors-C (VEGF-C) and -D (VEGF-D), as well as reliable lymphatic markers that have allowed observation and isolatio


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