血小板反应素-1在胃癌及转移淋巴结中的表达及其与血管生成相关性的研究

Expression of Thromhospondin-1 in Gastric Cancer and Metastatic Lymph Node Tissues and Its Relationship to Tumor Angiogenesis

目的检测血小板反应素-1(TSP-1)在原发性胃癌及转移淋巴结组织中的表达情况,并分析其与胃癌临床病理学参数及血管生成的关系。方法应用免疫组织化学方法检测72例成对胃癌组织、癌旁正常组织(距离癌灶≥5 cm)及胃周淋巴结组织中TSP-1及血管内皮生长因子(VEGF)的表达和微血管密度(MVD)的变化。采用半定量评分系统评估染色结果,并分析TSP-1蛋白表达与VEGF、MVD及胃癌临床病理学参数的关系。结果①TSP-1蛋白在胃癌组织中表达阳性率为45.8%(33/72),在癌旁正常组织中为90.3%(65/72),在转移淋巴结组织中为50.8%(30/59),其在胃癌组织和转移淋巴结组织中的蛋白表达阳性率明显低于其在癌旁正常组织中的表达阳性率(χ2=32.710,P=0.000;χ2=25.298,P=0.000),其在胃癌组织中的蛋白表达阳性率与其在转移淋巴结组织中的表达阳性率比较,差异无统计学意义(χ2=0.327,P=0.568)。②胃癌组织中TSP-1蛋白表达阳性率与淋巴结转移有关,即在有淋巴结转移的胃癌组织中TSP-1蛋白表达阳性率明显低于其在无胃周淋巴结转移组织中的表达阳性率(Z=-2.573,P=0.010)。③TSP-1在胃癌组织及转移淋巴结组织中的蛋白表达与VEGF表达(r s=-0.309,P=0.008;r s=-0.269,P=0.040)及MVD(r s=-0.348,P=0.003;r s=-0.272,P=0.037)呈负相关。结论TSP-1在胃癌组织及转移淋巴结组织中的蛋白表达均降低且与VEGF表达和MVD呈负相关,提示TSP-1可能是一个肿瘤血管生成抑制因子。

Objective To detect the expression of thromhospondin-1 （TSP-1） in gastric cancer and metastatic lymph node tissues, and to study its relationship of TSP-1 to clinicopathologic parameters or tumor angiogenesis. Methods The TSP-1 and vascular endothelial growth factor （VEGF） expressions and microvessel density （MVD） were evaluated by immunohistochemistry in 72 specimens obtained by gastric resection from patients with gastric cancer, including corresponding adjacent normal gastric mucosa tissues （distant from cancer ≥ 5 cm） and lymph nodes surrounding cancer. A semiquantitative scoring system was used for evaluating the staining. The relationship of TSP-1 to VEGF expression, MVD, or clinicopathologic parameters was analyzed. Results ① TSP-1 positive expression rate was 45.8% （33/72） in the primary gastric cancer tissues, 90.3% （65/72） in the corresponding adjacent normal gastric mucosa tissues, and 50.8% （30/59） in the metastatic lymph nodes tissues. The expressions of TSP-1 in the primary gastric cancer tissues and metastatic lymph nodes tissues were significantly lower than those in the adjacent normal gastric mucosa tissues （X32. 710, P=0. 000; X=25.298, P=0. 000）. The expression of TSP-1 had no statistical significance in the primary gastric cancer tissues as compared with in the metastatic lymph nodes tissues 0f=0. 327, P=0. 568）. ② The expression of TSP-1 in the metastatic lymph nodes tissues was significantly lower than that in the non-metastatic lymph nodes tissues （Z=-2. 573, P=0. 010）. ③ The expression of TSP-1 in the primary gastric cancer tissues and metastatic lymph nodes tissues suggested a negative correlation with VEGF （rs=-0. 309, P=0. 008; rs=-0. 269, P=0. 040） and MVD （rs=-0. 348, P=0. 003; r=-0. 272, P=0. 037）. Conclusions TSP-1 expression is down-regulated and has a negative correlation with VEGF and MVD in the primary gastric cancer and the metastatic lymph nodes tissues. According to the present results, it seems likely that TSP-1 is a tumor angiogenesis inhibitor.