Lymphangiogenesis in gastric carcinoma correlates with prognosis
Lymphangiogenesis in gastric carcinoma correlates with prognosis
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DOI：
10.1002/path.2523
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发表时间：
2009-06-01
影响因子：
7.3
通讯作者：
Mu, Kun
中科院分区：
文献类型：
--
作者：
Gao, Peng;Zhou, Geng-Yin;Mu, Kun
淋巴结转移是胃癌扩散的重要途径。然而，胃癌淋巴管生成的机制及其临床意义尚不清楚。在本研究中，淋巴管密度（LVD），VEGF-C的表达，和淋巴管内皮细胞的增殖活性测定在人胃癌和胃癌细胞裸鼠移植瘤。研究淋巴管生成的发展及其与患者预后的关系。结果表明，淋巴管主要分布于肿瘤周围，肿瘤周围LVD（P-LVD）显著高于肿瘤内LVD（I-LVD）（P < 0.05）。VEGF-C在肿瘤内的表达是不均匀的，边缘的表达（免疫染色评分）明显高于肿瘤中心（P < 0.05）。边缘VEGF-C表达与P-LVD呈显著相关（r = 0.72，p < 0.01），而中心VEGF-C表达与P-LVD无相关性（r = 0.72，p < 0.01）。外周组织中淋巴管内皮细胞增殖活性也较高，且淋巴管内皮细胞增殖活性与VEGF-C表达呈显著相关（P < 0.05）。这些数据表明，增加的突触可能是在VEGF-C刺激后新形成的。胃癌边缘VEGF-C的高表达可诱导癌周间质淋巴管生成，并导致P-LVD的增加。小鼠肿瘤移植物的数据也表明，从移植的胃癌细胞产生的VEGF-C可以诱导其周围的淋巴管生成。在患者中，肿瘤边缘VEGF-C表达与淋巴结转移、淋巴管浸润、无复发生存率和总生存率相关，可作为胃癌患者的独立预测因子。版权所有（c）2009大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
Lymphatic metastasis is an important way that gastric carcinomas can spread. However, little is known about the mechanisms of lymphangiogenesis and its clinical significance in gastric carcinomas. In the present study, lymphatic vessel density (LVD), VEGF-C expression, and proliferative activity of lymphatic endothelium were determined in human gastric carcinomas and xenografts of gastric cancer cells in nude mice. The development of lymphangiogenesis and its correlation with patient prognosis were investigated. The results showed that lymphatic vessels were observed mainly in peripheral tumour tissue with significantly (p < 0.05) higher P-LVD (peri-tumoural-LVD) than I-LVD (intra-tumoural-LVD). The expression of VEGF-C was heterogeneous within tumours, with a significantly higher expression (immunostaining score) at the margin than at the tumour centre (P < 0.05). A significant correlation was found between VEGF-C expression at the margin (but not at the centre) and P-LVD (r = 0.72, p < 0.01). High proliferative activity of lymphatic endothelium was also observed in the peripheral tissues, with a significant correlation between proliferative activity of lymphatic endothelium and VEGF-C expression (P < 0.05). These data imply that the increased lymphatics may have been newly formed following stimulation by VEGF-C. High VEGF-C expression at the margin of gastric carcinomas could induce lymphangiogenesis in the peri-tumoural stroma and contribute to the increased P-LVD. The data from mice tumour xenografts also suggested that VEGF-C produced from the transplanted gastric carcinoma cells could induce lymph angiogenesis around them. In patients, VEGF-C expression at tumour margins was associated with nodal metastasis, lymphatic vessel invasion, poor recurrence-free survival, and poor overall survival, and could serve as an independent predictor for patients with gastric carcinoma. Copyright (c) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.