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目的探讨神经细胞黏附分子———接触蛋白-1(CNTN-1)、血管内皮生长因子-C(VEGF-C)及其受体VEGFR-3(Flt-4)在原发性胃癌组织中的表达,并分析三者的相关性及其与临床病理特征的关系。方法选取68例原发性胃癌患者肿瘤原发灶和正常胃黏膜组织标本,行免疫组化染色检测VEGF-C、VEGFR-3和CNTN-1蛋白表达,测定VEGFR-3阳性淋巴管密度(FVD)和D2-40阳性淋巴管密度(LVD)。结果胃癌组织中VEGF-C、VEGFR-3和CNTN-1蛋白表达阳性率分别为57.4%(39/68)、60.3%(41/68)和55.9%(38/68),显著高于正常胃黏膜组织〔20.6%(14/68)、23.5%(16/68)、16.2%(11/68)〕,P=0.000。在TNM分期较晚、发生淋巴管浸润和淋巴结转移的患者其肿瘤组织中三者的表达阳性率均较高(P<0.05)。CNTN-1蛋白表达与VEGF-C(r=0.372,P=0.002)及VEGFR-3蛋白(r=0.308,P=0.011)表达之间呈正相关。68例患者肿瘤组织中FVD为(10.41±9.38)个/HP,明显低于其LVD〔(18.19±7.44)个/HP〕,P=0.000。在TNM分期较晚、有淋巴管浸润和淋巴结转移的患者肿瘤组织中,FVD与LVD均较高(P<0.05)。VEGF-C和CNTN-1蛋白表达阳性者FVD明显高于表达阴性者(P=0.029和P=0.003);LVD与CNTN-1(P=0.727)、VEGF-C(P=0.173)和VEGFR-3蛋白(P=0.924)表达均无关。VEGF-C、VEGFR-3及CNTN-1蛋白表达阳性患者术后生存率分别较表达阴性患者低(P<0.05)。结论 CNTN-1蛋白在胃癌组织中高表达,与VEGF-C和VEGFR-3蛋白表达相关,联合检测对判断胃癌侵袭性和预后有重要参考价值。VEGF-C可能通过CNTN-1通路介导淋巴管生成,从而促进胃癌的淋巴浸润。
Objective To investigate the expression of vascular endothelial cell adhesion molecule-1 (CNTN-1), vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 Expression, and analysis of the correlation between the three and its relationship with clinicopathological features. Methods 68 cases of primary gastric cancer patients with primary tumor and normal gastric mucosa specimens were detected by immunohistochemical staining of VEGF-C, VEGFR-3 and CNTN-1 protein expression, VEGFR-3 positive lymphatic vessel density (FVD ) And D2-40 positive lymphatic vessel density (LVD). Results The positive rates of VEGF-C, VEGFR-3 and CNTN-1 in gastric cancer tissues were 57.4% (39/68), 60.3% (41/68) and 55.9% (38/68), respectively, which were significantly higher than those in normal gastric Mucosal tissues [20.6% (14/68), 23.5% (16/68), 16.2% (11/68)], P = 0.000. In TNM stage, the patients with lymphatic invasion and lymph node metastasis had a higher positive expression rate (P <0.05). The expression of CNTN-1 protein was positively correlated with the expression of VEGF-C (r = 0.372, P = 0.002) and VEGFR-3 protein (r = 0.308, P = 0.011) The FVD in 68 patients was (10.41 ± 9.38) / HP, which was significantly lower than that of LVD (18.19 ± 7.44) /PHP, P = 0.000. FVD and LVD were higher in patients with TNM stage, lymph node invasion and lymph node metastasis (P <0.05). FVD was significantly higher in patients with positive expression of VEGF-C and CNTN-1 than those with negative expression (P = 0.029 and P = 0.003) 3 protein (P = 0.924) expression was not related. The postoperative survival rates of patients with VEGF-C, VEGFR-3 and CNTN-1 protein expression were lower than those with negative expression (P <0.05). Conclusion The high expression of CNTN-1 protein in gastric carcinoma is correlated with the expression of VEGF-C and VEGFR-3 protein. The combined detection of CNTN-1 protein is of great value in judging the invasiveness and prognosis of gastric carcinoma. VEGF-C may mediate lymphangiogenesis through the CNTN-1 pathway, thereby promoting lymph node infiltration of gastric cancer.