胃癌细胞间黏附分子-1与VEGF-D的关系及意义

The relationship between expression of ICAM-1 and VEGF-D in gastric cancer and its significance

目的:研究细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)与血管内皮生长因子受体-3(vascular endo-thelial growth factor receptor-3,VEGFR-3)信号通路的关系,从而揭示胃癌淋巴管转移的部分机制。方法:选择胃癌患者100例,其中早期胃癌13例,进展期胃癌87例(无淋巴结转移者37例,有淋巴结转移者50例);取距胃癌病灶>5cm处的正常胃黏膜标本30例为对照组。利用免疫组织化学法检测对照组和胃癌组织中血管内皮生长因子-C(vascular endothelial growth factor-C,VEGF-C)、VEGF-D、VEGFR-3、ICAM-1和肿瘤新生淋巴管密度。观察胃癌组织中淋巴管、血管受侵情况。结果:ICAM-1阳性表达随肿瘤浸润深度增加而增加,对照组、早期胃癌和进展期胃癌的ICAM-1阳性表达率分别是0%、7.7%和31.0%(P<0.05);ICAM-1阳性表达与淋巴结转移、淋巴管受侵、VEGF-C和VEGF-D阳性表达有关(分别为P<0.005,P<0.025,P<0.025,P<0.005)。Logistic回归分析显示,ICAM-1阳性表达与淋巴结转移和VEGF-D阳性表达相关(P=0.0012,P=0.0237)。结论:ICAM-1阳性表达与VEGF-D阳性表达呈正相关,其机制可能是VEGF-D通过VEGFR-2信号途径调节ICAM-1表达,从而在胃癌淋巴管转移中发挥作用。

Objective：To investigate the relationship between intercellular adhesion molecule-1 （ICAM-I） and the signaling pathway of vascular endothelial growth factor receptor-3 （ VEGFR-3 ） in gastric cancer and explore the mechanism underlying the lymphatic metastasis of gastric cancer. Methods ：Totally 100 grastic cancer patients were recruited in the study including 13 cases of early gastric cancer and 87 cases of advanced gastric cancer with lymphatic metastasis （ 50 cases） and without lymphatic metastasis （ 37 cases）. Thirty cases of normal gastric mucosa in the distance of 〉 5 cm from gastric cancer lesions were used as controls. The expres- sions of VEGF-C, VEGF-D, VEGFR-3, ICAM-1 and lymphatic microvessel density （LMVD） were detected using immunohistochemical method （EnVisionTM）. The lymphatic and vascular invasions of gastric cancer were observed by microscopy. Results： The positive expression rate of ICAM-1 was increased with the increase in infiltration depth. It was 0% in the control, 7.7% in early stage gastric cancer, and 31.0% in advanced gastric cancer, respectively （P 〈 0.05）. The positive rate of ICAM-1 expression was related with lym- phatic metastasis （P 〈 O. 005 ）, depth of tumor invasion （ P 〈 O. 025 ）, VEGF-C expression （ P 〈 0. 025 ）, and VEGF-D expression （P 〈0. 005）. Logistic regression analysis showed that the positive expression of ICAM-1 correlated with lymph node metastasis and expression of VEGF-D （P = 0. 001 2, P = 0. 023 7）. Conclusion： ICAM-1 expression has positive correlation with expression of VEGF-D. The mechanism may be contributed to regulation of ICAM-1 expression by VEGF-D via VEGFR-2 signaling pathway.