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

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。

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： Immunohistochemic 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.