血管内皮生长因子D和血管内皮生长因子受体3在人结肠癌中的表达及淋巴道转移中的作用

THE EXPRESSIONS OF VEGF-D AND VEGFR-3 IN COLON CARCINOMA AND THEIR ROLE IN LYMPHATIC METASTASIS OF CARCINOMA

目的观察血管内皮生长因子D(VEGF-D)和血管内皮生长因子受体3(VEGFR-3)在人结肠癌组织中的表达,检测结肠癌组织中的微淋巴管密度(LMVD),探讨VEGF-D和VEGFR-3在淋巴管生成以及结肠癌淋巴道转移中的作用。方法选择55例不同时期,不同分化程度的人结肠癌组织样本,应用免疫组织化学染色的方法,观察VEGF-D和VEGFR-3在人结肠癌组织中的表达,应用Podoplanin标记淋巴管,检测结肠癌组织中的淋巴管密度。结果在55例结肠癌组织中,VEGF-D的阳性表达率为54.5%,明显高于在癌周正常组织内的表达(P<0.05);结肠癌组织中VEGFR-3表达的阳性率为69.1%,明显高于在癌周正常组织内的表达(P<0.01);并且VEGFR-3的表达与VEGF-D的表达具有显著相关性(P<0.01)。在结肠癌组织中,淋巴结转移阳性组,浸润深度超过肌层组,DukeC、D期的VEGF-D的表达水平和LMVD明显高于淋巴结转移阴性组,浸润深度未超过肌层组,Duke A、B期(P<0.01),经计数淋巴管数量,癌组织中的LMVD明显高于癌周正常组织(P<0.01),并且LMVD与VEGF-D的表达显著相关(P<0.01)。结论结肠癌组织中VEGF-D的表达水平随着癌的浸润和转移程度的增强而增高,并且通过上调其受体VEGFR-3的表达而促进癌组织中淋巴管的生成,从而促进癌的浸润和转移。

Objective To investigate the role of vascular endothelial growth factor D （VEGF-D） and vascular endothelial growth factor receptor 3 （VEGFR-3） in lymphangiogenesis and lymphatic metastasis of colon carcinoma by observing the expression of VEGF-D and VEGFR-3, and calculated lymphatic vessel density （LMVD） in colon carcinoma. Methods The expressions of VEGF-D and VEGFR-3 were observed by SP immunohistochemistry in 55 colon carcinoma samples of different stages and differentiation degrees. LMVD in colon carcinoma was calculated by using Podoplanin as the specific marker of lymphatic endothelium. Results The positive expression of VEGF-D in colon carcinoma （54.5%） was higher than that in pefitumoral tissues （ P 〈 0.05）, and the expression rate of VEGFR-3 （69.1% ） was higher than that in pefitumoral tissues （ P 〈 0.01 ）. The obvious correlation can be seen between the expressions of VEGF-D and VEGFR-3 （P 〈 0.01 ） in colon carcinoma. We found that LMVD in carcinoma was higher than that in peritumoral tissues and the expression of VEGF-D in the groups with lymph nodes metastasis and invaded muscular layer and in phases Duke＇ s C and D was higher than that in the groups without lymph nodes metastasis, and non-invaded muscular layer and in phases Duke＇s A and B （P 〈 0.05）. The correlation can be seen obviously between LMVD and the expression of VEGF-D（ P 〈 0.01 ）. Conclusion The positive expression of VEGF-D in colon carcinoma is related with the tumor progression. It seems that VEGF-D induces lymphangiogenesis through its receptor VEGFR-3. VEGF-D and VEGFR-3 might play an important role in colon carcinoma metastasis via lymphatics.