结直肠癌组织中VEGF-C、VEGFR-3的表达及意义

The Expression and Significance of VEGF-C and VEGFR-3 in Colorectal Carcinoma

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:选取CRC组织50例,结直肠腺瘤组织20例,正常小肠组织20例,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组织中的表达率分别为44%(22/50)、36%(18/50),而在腺瘤组织及正常小肠黏膜组织中均不表达;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<0.01),不同年龄、性别、TNM分期、Duke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CRC组织的LVD高于阴性组(P<0.001);多因素Logistic回归分析提示VEGF-C和VEGFR-3蛋白阳性表达是CRC发生淋巴结转移的独立危险因素。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。

Objective： To investigate the relationship between the expressions of vascular endothelial growth factor-C （VEGF-C）, vascular endothelial growth factor receptor-3 （VEGFR-3）, lymphangiogenesis and lymph node metastasis in colorectal cancer. Methods： The immunohistochemical SP method was used to detect the expression levels of VEGF-C and VEGFR-3 protein in 50 colorectal cancer tissue samples, 20 colorectal adenoma tissue samples and 20 normal tissue samples. Meanwhile, lymphatic vessel density （LVD） was evaluated with lymphatic endothelium-specific marker, lymphatic vessel endothelial hyaluronan receptor-1 （LYVE-1）. Results： The positive rates of VEGF-C and VEGFR-3 proteins were 44% （22/50） and 36% （18/50） in colorectal cancer, respectively. However, VEGF-C and VEGFR-3 expressions were not found in colorectal adenoma tissue and normal tissue samples. There were significant differences in expressions of VEGF-C and VEGFR-3 proteins between patients with and without lymph node metastasis （P 〈 0.001）. There were no significant differences in expressions of VEGF-C and VEGFR-3 proteins between different age, gender, TNM stage,Dukes stage, Broder stage, histological type and invasion depth groups （P 〉 0.05）. The values of LVD were significantly higher in VEGF- C-positive and VEGFR-3-positive groups than those of VEGF-C-negative and VEGFR-3-negative groups （P 〈 0.001）. Multivariate analysis revealed that VEGF-C-positive and VEGFR-3- positive expressions were independent factors associated with lymph node metastasis in colorectal cancer. Conclusion： This study suggested that the expression of VEGF- C and VEGFR-3 contributed to the 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.