Coexpression of VEGF-C and COX-2 and its association with lymphangiogenesis in human breast cancer.
Coexpression of VEGF-C and COX-2 and its association with lymphangiogenesis in human breast cancer.
复制标题
DOI：
10.1186/1471-2407-8-4
复制
发表时间：
2008-01-13
期刊：
影响因子：
3.8
通讯作者：
Chen SY
中科院分区：
文献类型：
--
作者：
Zhang XH;Huang DP;Guo GL;Chen GR;Zhang HX;Wan L;Chen SY
自从发现了能够观察和分离淋巴管内皮细胞的可靠的淋巴管标志物以来，淋巴管生成已经成为肿瘤转移研究的新前沿。环氧合酶-2(COX-2)被认为参与了肿瘤发生的关键步骤。然而，COX-2在淋巴管生成和淋巴转移中的可能作用仍然知之甚少。本研究旨在探讨乳腺癌组织中血管内皮生长因子-C(VEGF-C)和环氧合酶-2(COX-2)的表达及其与淋巴管生成和预后的关系。采用免疫组织化学方法检测70例乳腺癌患者原发肿瘤组织中血管内皮生长因子-C、环氧合酶-2和D2-40的表达。分析COX-2和VEGF-C的表达与临床病理参数及预后的关系。为显示淋巴管内皮细胞的存在，随机选择10例LVD计数较高的病例进行D2-40/Ki-67双重免疫组织化学染色。血管内皮生长因子-C与环氧合酶-2的表达呈正相关(r=0.529，P<；0.001)，单因素分析显示，血管内皮生长因子-C的高表达和环氧合酶-2的高表达均与高淋巴管密度、淋巴结转移和D2-40阳性淋巴侵袭、无瘤生存期和总生存期有关。在淋巴管标记物D2-40和增殖标记物Ki-67的双重免疫染色中，结果证实部分淋巴管内皮细胞有Ki-67阳性核。乳腺癌中确实有淋巴管生成，最令人信服的证据是存在增殖的淋巴管内皮细胞。血管内皮生长因子-C和环氧合酶-2在浸润性乳腺癌中共同表达，与淋巴管生成和预后密切相关。提示COX-2可能通过淋巴管生成途径上调血管内皮生长因子-C的表达，从而促进乳腺癌的淋巴转移。
Lymphangiogenesis has become a new research frontier in tumor metastasis since the discovery of reliable lymphatic markers that have allowed observation and isolation of lymphatic endothelium. Cyclooxygenase-2 (COX-2) has been reported to be involved in the critical steps in carcinogenesis. However, possible role of COX-2 in lymphangiogenesis and lymphatic metastasis is still poorly understood. In present study, we aimed to investigate the relationship between vascular endothelial growth factor-C (VEGF-C) and COX-2 in human breast cancer, and correlations with lymphangiogenesis and prognosis. 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.
登录
查看更多内容
影响因子：
82.9
作者：
Skobe, M;Hawighorst, T;Detmar, M
通讯作者：
Detmar, M
影响因子：
7.5
作者：
Kyzas, PA;Stefanou, D;Agnantis, NJ
通讯作者：
Agnantis, NJ
DOI：
10.1111/j.1440-1746.2004.03348.x
发表时间：
2004-06-01
影响因子：
4.1
作者：
Byeon, JS;Jung, HY;Kim, JS
通讯作者：
Kim, JS
影响因子：
3.8
作者：
Kinoshita, J;Kitamura, K;Sugimachi, K
通讯作者：
Sugimachi, K
影响因子：
8.8
作者：
通讯作者：
--