Toll样受体4在胃食管交界部腺癌发展中的作用及与血管密度的关系

Relationship between TLR4 expression and angiogenesis in human AEJ

目的 :探讨Toll样受体4(TLR4)在胃食管交界部腺癌发展中的作用及其与血管生成之间的关系。方法 :采用回顾分析,通过免疫组化法检测43例(其中23例为随访证实已出现复发转移)经病理证实的胃食管交界部腺癌手术切除标本中TLR4蛋白的表达;采用CD34抗体标记微血管内皮细胞,计算微血管密度(MVD)。分析TLR4蛋白的表达、MVD与胃食管交界部腺癌主要临床病理参数以及预后的关系。结果:TLR4蛋白的阳性表达率为69.8%,其中A组(复发转移组)TLR4蛋白阳性率为82.6%,明显高于对照组B组(55.0%,P<0.05);有淋巴结转移者的TLR4蛋白阳性表达率(79.3%)高于无淋巴结转移者(50.0%,P=0.05);TNM分期为Ⅲ+Ⅳ期者的TLR4蛋白阳性表达率(82.8%),明显高于Ⅰ+Ⅱ期者(42.9%,P<0.01)。TLR4蛋白的表达与MVD呈正相关(P=0.008)。结论:TLR4的高表达与胃食管交界部腺癌的发生发展及患者的预后情况密切相关,可能与TLR4促进肿瘤微血管生成相关。

Objective：To investigate the effects of Toll-like receptor 4 overexpression in human AEJ and the relationship between TLR4 overexpression and angiogenesis. Methods：Through retrospective analysis, a total of 43 surgically resected human AEJ specimens were investigated for TLR4 protein expression by immunohistochemical SP methods,CD34 antibody was used to mark microvascular endothelial cells and the microvessel density（MVD） was determined The correlation among TLR4 protein expression and MVD and clinicopathologic features of AEJ was analyzed. Results：TLR4 protein positive rate was 69.8%, rate of 82.6% in group A which was metastasis and recurrence was significantly higher than that of the control group B（P 〈 0.05）. TLR4 protein positive rate in the cases with lymph node metastasis（79.3%）was significantly higher than that in the cases without lymph node metastasis（50.0%） （P=0.05）. TLR4 protein positive rate in the patients with stage Ⅲ and IV of TNM classification was 82.8%, which was significantly higher than that in the patients with stage I and Ⅱ （42.9%,P 〈 0.05）. MVD was closely related to TNM stage of AEJ （P=0.008）. There was a strong positive correlation between TLR4 protein expression and MVD（P=0.012）. There was no statistical significance among tumor grade,size,vascular metastasis,and neural invasion. Conclusions：TLR4 expression was closely related to the progression of tumor and prognosis of patients and might be related to the promotion of tumor angiogenesis.