天津医药

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结直肠癌组织中VEGF-C、VEGFR-3的表达及意义

裴永彬,刘云,贺新奇,张峰,高英超,赵增仁   

  1. 河北医科大学第一医院
  • 收稿日期:2012-04-05 修回日期:2012-07-13 出版日期:2012-10-15 发布日期:2012-10-15
  • 通讯作者: 赵增仁

Expression and significance of VEGF-C and VEGFR-3 in colorectal carcinoma

  • Received:2012-04-05 Revised:2012-07-13 Published:2012-10-15 Online:2012-10-15

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摘要： 摘要 目的 探讨结直肠癌（CRC）组织中血管内皮生长因子-C（VEGF-C）、血管内皮生长因子受体-3（VEGFR-3）的表达与新生淋巴管及淋巴结转移的关系。方法 分别选取临床病理资料完整的CRC组织与结直肠腺瘤组织50例、20例，另取20例正常小肠组织作为阴性对照组，采用免疫组织化学SP法检测样本中 VEGF-C、VEGFR-3蛋白的表达，用淋巴管内皮透明质酸受体-1(LYVE-1）特异标记淋巴管计数各样本的淋巴管密度(LVD)。结果 VEGF-C、VEGFR-3蛋白在CRC组中的表达率分别为44%、36%，而在腺瘤组及正常小肠粘膜组中均不表达；在有无淋巴结转移的患者中VEGF-C及VEGFR-3蛋白的表达差异均有统计学意义（P＜0.001），不同年龄、性别、TNM分期、Dukes分期、Broder分级、肿瘤浸润深度、组织学类型VEGF-C及VEGFR-3蛋白的表达差异均无统计学意义（P＞0.05）。在VEGF-C、VEGFR-3表达阳性的CRC组织中LVD均明显高于阴性组（P＜0.001）；单变量分析显示Broder分级、VEGF-C及VEGFR-3蛋白阳性表达是发生淋巴结转移的预测因素(（P=0.024，P＜0.001，P＜0.001)，而多变量分析提示VEGF-C和VEGFR-3蛋白阳性表达是淋巴结转移的独立危险因素(P=0.001；P=0.02)。结论 CRC组织中 VEGF-C、VEGFR-3蛋白的高表达与新生淋巴管的形成及发生淋巴结转移有关，VEGF-C、VEGFR-3可能作为CRC患者生物治疗的新靶点。

关键词: 结直肠癌, 新生淋巴管, 血管内皮细胞生长因子-C, 血管内皮细胞生长因子受体-3, 淋巴结转移

Abstract: Abstract Objective: To investigate the relationship between the expression of vascular endothelial growth factor-C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3) and lymphangiogenesis, lymph node metastasis in colorectal cancer. Methods: Fifty colorectal cancer tissues and twenty colorectal adenoma tissues were selected randomly, meanwhile twenty normal tissues were selected as negative control group. Immunohistochemistry was used to detect the expression of VEGF-C and VEGFR-3. Lymphatic vessel density(LVD) was evaluated with lymphatic endothelium-specific marker, lymphatic vessel endothelial hyaluronan receptor-1(LYVE-1). All specimens had complete clinicopathologic data. Results: The positive rates of VEGF-C and VEGFR-3 expression in colorectal cancer were 44% and 36%, respectively. However, VEGF-C and VEGFR-3 expression were not found in colorectal adenoma tissues and normal tissues. There were significant differences in expressions of VEGF-C and VEGFR-3 proteins between patients with and without lymph node matastasis (P<0.001). There were no significant differences between gender, age, TNM stage，Dukes stage, Broder stage, histological type and invasion depth in CRC(P>0.05). LVDs were significantly higher in VEGF-C-positive and VEGFR-3-positive tumors compared with VEGF-C-negative and VEGFR-3-negative tumors(P<0.001). Univariate analysis revealed that Broder stage, VEGF-C-positive and VEGFR-3- positive were predictive factors of lymph node metastasis((P=0.024, P＜0.001, P＜0.001). Multivariate analysis revealed that the independent factors associated with lymph node metastasis were VEGF-C and VEGFR-3(P=0.001, P=0.02). Conclusions: This study suggests that the expression of VEGF-C and VEGFR-3 contributed to lymphangiogenesis and lymph nodal metastasis in colorectal cancer. VEGF-C and VEGFR-3 may serve as a new target of biological therapy in colorectal cancer. Key Words colorectal cancer, VEGF-C, VEGFR-3, lymphangiogenesis, lymph node metastasis

Key words: colorectal cancer, VEGF-C, VEGFR-3, lymphangiogenesis, lymph node metastasis