Notch1和HER2在胃癌中的表达及临床意义
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Expression and clinical significance of Notch1 and HER2 in gastric carcinoma
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    目的:探讨Notch1和人类表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)在胃癌中的表达及临床意义-方法:采用免疫组化检测317例胃癌组织芯片中Notch1的表达,采用免疫组化和FISH分别检测HER2蛋白过表达和基因扩增情况-结果:64例(20.2%)胃癌组织呈HER2蛋白过表达,58例(18.3%)呈HER2基因扩增,HER2蛋白过表达与基因扩增一致率为89.1%-HER2在不同肿瘤部位-组织学类型之间表达存在显著性差异(P < 0.01);在不同分化程度-临床TNM分期之间差异无统计学意义(P > 0.05)-197例(62.1%)胃癌组织表达Notch1,Notch1表达在不同肿瘤分化程度-临床分期之间存在显著性差异(P < 0.05)-关联分析显示Notch1表达与HER2蛋白过表达和基因扩增均存在显著负相关(分别r = -0.191,P < 0.01;r = -0.169,P < 0.01)-结论:胃癌中存在Notch1显著高表达,Notch1高表达促进胃癌的生长和浸润,患者往往具有高临床分期-HER2过表达与Notch1高表达之间存在显著负相关关系,提示Notch1可以作为胃癌新的候选治疗靶分子-

    Abstract:

    Objective: To study the expression and clinical significance of Notch1 and human epidermal growth factor receptor 2(HER2) in gastric carcinoma. Methods: The expression of Notch1 was detected by immunohistochemistry,and assessment of HER2 protein overexpression and gene amplification were done by immunohistochemistry and fluorescence in situ hybirdizaton(FISH) in tissue microarrays containing 317 gastric carcinomas and relatively normal gastric mucosa tissue. Results: Overexpression of HER2 protein was observed in 64 cases(20.2%) and HER2 gene amplification was detected in 58 cases(18.3%) of gastric carcinoma. The concordance rate between the immunohistochemistry and FISH was 89.1%. HER2 protein overexpression and gene amplification were significantly associated with tumor location and the Laurén’s classification(P < 0.01),but not with differentiation grade and clinical stage (P > 0.05). The expression of Notch1 protein was observed in 197 cases (62.1%) of gastric carcinoma,and was significantly associated with differentiation grade and clinical stage(P < 0.05). The expression of Notch1 was negatively correlated to the protein overexpression and gene amplification of HER2 (r = -0.191,P < 0.01;r = -0.169,P < 0.01,respectively). Conclusion: The significantly dys-regulated expression of Notch1,which could promote growth and invasion of gastric carcinoma cells and correlated to the higher clinical TNM stage,was observed in gastric carcinoma. The expression of Notch1 negatively correlated to the protein overexpression and gene amplification of HER2 suggests that Notch1 may act as a novel therapeutic target molecule for gastric carcinoma.

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刘 标,孙利兵,陈伟群,周俊东,吴锦昌. Notch1和HER2在胃癌中的表达及临床意义[J].南京医科大学学报(自然科学版),2012,(2):236-240

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  • 收稿日期:2011-09-23
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