淋巴管密度和功能形态与膀胱癌淋巴结转移关系的研究

The association of lymphatic vessel density and functional configuration with lymph node metastasis in bladder cancer

目的探讨膀胱癌淋巴管密度、功能形态变化在膀胱癌淋巴结转移中的意义。方法采用血管内皮生长因子受体3(VEGFR-3)免疫组化方法研究肿瘤组织内和瘤周淋巴管形态结构,并计数淋巴管密度;RT-PCR方法研究36例膀胱移行细胞癌和8例正常膀胱组织中血管内皮生长因子C(VEGF-C)表达情况及其与膀胱癌淋巴管密度、淋巴结转移的关系。结果VEGFR-3表达于淋巴管内皮细胞胞质。随着VEGF-C表达增强,瘤内、瘤周淋巴管密度明显增加(13.45±2.04 vs9.38±1.96,20.25±1.89 vs 14.25±1.44,P<0.05),同时膀胱癌淋巴管浸润、淋巴结转移也明显增加(P<0.05)。结论膀胱癌VEGF-C/VEGFR-3途径促进淋巴管新生、肿瘤淋巴管浸润和淋巴结转移。阻断VEGF-C/VEGFR-3通路将抑制淋巴管形成,可能成为膀胱癌治疗的新靶点。

Objective To determine the intra- and peri-tumoral lymphatic vessel density （LVD） and its correlation with lymph node metastasis in bladder transitional cell carcinoma （BTCC）. Methods In 36 samples of BTCC, the lymphatic vessels immunostained with monoclonal antibodies against vascular endothelial growth factor receptor 3 （VEGFR-3） and LVD were evaluated in both intra- and peri-tumoral areas. Then the levels of expression of vascular endothelial growth factor C （VEGF-C） by RT-PCR and its correlation with LVD and lymph node metastasis were assessed in 36 samples of BTCC and 8 normal bladder tissues. Results VEGFR-3 was expressed in lymphatic vessel endothelial cytoplasm. As the expression level of VEGF-C became stronger, the intra- and peri-tumoral LVD increased significantly （ 13.45 ± 2.04 vs 9.38 ± 1.96 ;20.25 ±1.89 vs 14.25 ± 1.44 ,respectively ：P 〈 0.05）. Meanwhile lymphatic invasion of bladder carcinoma and lymph node metastasis increased significantly （P 〈 0.05）. Conclusions It is suggested that in BTCC, VEGF-C/VEGFR-3 pathway can contribute to lymphangiogenesis,lymphatic invasion of tumor and lymph node metastasis. Therefore, blocking VEGF-C/VEGFR-3 pathway can inhibit lymphangiogenesis,which will be a new target for treatment of BTCC.