人表皮生长因子受体2、核因子-κB及血管内皮生长因子在胃癌组织中的表达及其临床意义

Expressions and clinical significance of human epidermal growth factor receptor-2,nuclear factor-κB and vascular endothelial growth factor in gastric carcinoma tissues

目的探讨胃癌组织中人表皮生长因子受体2(HER-2)、核因子-κB(NF-κB)及血管内皮生长因子(VEGF)的表达情况及其临床意义。方法应用免疫组织化学方法(S-P法)检测126例胃癌组织、54例正常胃黏膜组织中HER-2、NF-κB及VEGF蛋白表达情况,分析三者的相关性及其表达与胃癌临床病理特征间的关系。结果 (1)胃癌组织中HER-2高表达率为21.4%(27/126),NF-κB及VEGF蛋白的阳性表达率分别为53.9%(68/126)、58.7%(74/126),均明显高于正常胃黏膜组织(P<0.05);(2)低分化胃癌组、淋巴结转移组、TNMⅢ+Ⅳ期组患者的胃癌标本中HER-2蛋白高表达率较高(P<0.05);低分化胃癌组、浆膜或浆膜外浸润组、TNMⅢ+Ⅳ期组患者的胃癌标本中NF-κB蛋白阳性率较高(P<0.05);浆膜或浆膜外浸润组、淋巴结转移组、TNMⅢ+Ⅳ期组患者的胃癌标本中VEGF蛋白阳性率较高(P<0.05)。(3)胃癌组织中HER-2与NF-κB、HER-2与VEGF、NF-κB与VEGF表达均呈正相关性(P<0.05)。结论胃癌组织中HER-2、NF-κB及VEGF的阳性表达增高。HER-2可激活NF-κB以影响胃癌的发展和预后,激活VEGF可促进肿瘤的生长与转移,三者的协同作用对于研究胃癌的信号传导网络及分子靶向药物治疗有重要意义。

Objective To investigate the expressions and clinical significance of human epidermal growth factor receptor-2 （HER-2）, nuclear factor-κB（NF-κB） and vascular endothelial growth factor（VEGF） in gastric carcinoma tissues. Methods The expressions of HER-2, NF-κB and VEGF proteins were detected by immunohistochemistry（S-P method） in 126 gastric carcinoma tissues and 54 normal gastric mucosa tissues. The correlation of the three proteins ,and the relationship of the protein expressions with clinical and pathological characteristics of gastric carcinoma were analyzed. Results ① In gastric carcinoma tissues, the overexpression rate of HER-2 was 21.4% （ 27/126 ）, the positive expression rates of NF-κB and VEGF protein were 53.9% （68/126） and 58.7% （74/126） respectively, which were significantly higher than those in normal gastric mucosa（ P 〈 0. 05 ）. ② The overexpression rates of HER-2 protein in gastric carcinoma specimens were higher in the poorly differentiated gastric carcinoma group,lymphatic metastasis group and TNM stage Ⅲ＋Ⅳ group （P 〈 0. 05 ）. The positive expression rates of NF-κB protein in gastric carcinoma specimens were higher in the poorly differentiated group, serosal or subserosal infiltration group and TNM stage Ⅲ＋Ⅳ group（ P 〈 0. 05 ）. The positive expression rates of VEGF protein in gastric carcinoma specimens were higher in serosal or subserosal infiltration group,lymphatic metastasis group and TNM stage Ⅲ＋Ⅳ group （P 〈 0. 05 ）. ③In gastric carcinoma tissues, the expression of HER-2 positively correlated with the expression of NF-κB or VEGF, and positive correlation also existed between NF-κB and VEGF expressions（ P 〈 0.05 ）. Conclusion The positive expressions of HER-2, NF-κB and VEGF increase in the gastric carcinoma tissues. HER-2 can activate NF- κB to affect the development and prognosis of gastric cancer,and activate VEGF to promote the growth and metastasis of tumor. The synergistic effect of HER-2,NF-κB and VEGF has a great significance in the study of signal transduction network and molecular-targeted drug therapy for gastric cancer.