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胃癌中组织因子途径抑制剂2的表达及其与预后和肿瘤血管生成模式的相关性研究
Expression of Tissue Factor Pathway Inhibitor-2 and Its Correlation with Prognosis and Tumor Angiogenesis Mode
【摘要】 目的:探讨胃癌中组织因子途径抑制剂2(tissue factor pathway inhibitor 2,TFPI-2)表达的临床意义及其与患者预后的关系,分析TFPI-2表达与胃癌组织中内皮依赖性血管和血管生成拟态的相关性。方法:采用免疫组化对187例胃癌标本进行TFPI-2蛋白表达检测,分析其与临床病理参数的关系。通过CD34免疫组化染色评价肿瘤组织微血管密度,CD34/PAS双重染色观察胃癌中血管生成拟态的分布特征。结果:胃癌组织中TFPI-2阳性表达率约为48.1%(90/187),TFPI-2蛋白表达与肿瘤分化程度、TNM分期、淋巴结转移、浸润深度及远处转移有关,而与患者性别、年龄、肿瘤部位、肿瘤最大径及临床分期无关。KaplanMeier分析表明与低、中表达组相比,TFPI-2高表达组患者总生存期和无瘤生存期明显延长。TFPI-2与血管生成模式相关性分析显示,在所有胃癌组织中TFPI-2与内皮依赖性血管呈负相关,与血管生成拟态无关。在中、高分化胃癌组织中,TFPI-2与内皮依赖性血管呈负相关,与血管生成拟态无关。在低分化胃癌中TFPI-2与血管生成拟态呈正相关。结论:随着肿瘤恶性程度的增加TFPI-2蛋白表达有所降低,TFPI-2表达与胃癌预后密切相关。在分化程度较高的胃癌组织中,TFPI-2通过抑制内皮依赖性血管,抑制肿瘤浸润和转移,具有抑制胃癌进展的作用;在恶性程度较高的低分化胃癌中,TFPI-2促进血管生成拟态的形成,提示TFPI-2在胃癌血管生成模式中可能起到双向调节作用。
【Abstract】 Objective:To investigate the clinical significance of tissue factor pathway inhibitor-2(TFPI-2 ) and its role in the prognosis of gastric cancer.This study also aims to analyze the correlation among TFPI-2,endothelium-dependent angiogenesis,and vasculogenic mimicry(VM ) in gastric cancer.Methods:Irnmunohistochemic staining was conducted to detect the expression of TFPI-2 protein and analyze its relationship with clinicopathological parameters from 187 gastric cancer cases.The microvessel density was measured through CD34 immunohistochemistry stain,and the distribution feature of VM was observed via CD34 / periodic acid-schiff double staining.Results: The positive expression rate of TFPI-2 was approximately 48.1%(90 / 187 ).The expression of the TFPI-2 protein was correlated with the tumor differentiation degree,tumor node metastasis stage,lymph node metastasis,invasion,and distant metastasis.However,it was not correlated with gender,age,tumor location,tumor maximal size,and clinical stage.The Kaplan-Meier survival analysis showed that patients with the higher expression of TFPI-2 had longer overall survival time and disease-free survival time than those with lower expression of TFPI-2.The relationship between TFPI-2 and tumor angiogenesis mode showed that TFPI-2 was negatively correlated with endotheli um-dependent angiogenesis.No correlation was found between TFPI-2 and VM in all samples of gastric cancer.In well-differentiated gastric cancer,TFPI-2 was negatively correlated with endothelium-dependent angiogenesis.TFPI-2 expression was not correlated with VM but was positively correlated with VM in poorly-differentiated gastric cancer.Conclusion:TFPI-2 expression decreased with the development of tumor malignancy degree and exhibited a significant effect on the prognosis of gastric cancer.In addition,TFPI-2 expression was closely correlated with endothelium-dependent angiogenesis.It inhibited invasion and metastasis,thus suppressing the progress of well differentiated gastric cancer.Moreover,TFPI-2 promoted the formation of vasculogenic mimicry in highly malignant and poorly differentiated gastric cancer. TFPI-2 may be a dual function regulator for angiogenesis mode in gastric cancer.
【Key words】 Gastric cancer; TFPI-2; Invasion; Metastasis; Vasculogenic mimicry; Endothelium-dependent angiogenesis;
- 【文献出处】 中国肿瘤临床 ,Chinese Journal of Clinical Oncology , 编辑部邮箱 ,2012年08期
- 【分类号】R735.2
- 【被引频次】7
- 【下载频次】77