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人结直肠癌组织中EGFR/Grb2/p-mTOR/VEGF的表达及意义
项洪刚,王强*,胡志前,徐健,王伟军,卫子然
0
(第二军医大学长征医院普外科,上海 200003)
摘要:
目的:观察人结直肠癌组织磷酸化哺乳动物雷帕霉素靶蛋白(phosphorylated mammalian target of rapamycin,p-mTOR)、表皮生长因子受体(EGFR)、生长因子受体结合蛋白2 (Grb2)和血管内皮生长因子(VEGF)等的表达,并探讨其可能的临床意义。方法:构建含有185例结直肠癌标本的组织芯片,免疫组化法检测结直肠癌组织及癌旁组织中EGFR、Grb2、p-mTOR和VEGF的表达,并分析不同结直肠癌临床病理学特征下(如年龄、性别、浸润深度、淋巴转移、临床分期和分化程度)各自的表达情况,探讨可能的临床意义。结果:EGFR、Grb2、p-mTOR和VEGF在结直肠癌旁组织中呈少量表达或不表达,在结直肠癌组织中的表达率分别为21.1%、44.9%、42.2%和54.1%,明显高于癌旁组织(P<0.05)。结直肠癌患者不同性别、年龄、肿瘤分化程度下EGFR、Grb2、p-mTOR和VEGF表达率无统计学差异;不同浸润深度和临床分期下EGFR的表达率有统计学差异(P<0.05);不同浸润深度、淋巴转移和临床分期下p-mTOR、VEGF表达率均有统计学差异(P<0.05)。结直肠癌组织EGFR/Grb2/p-mTOR/VEGF蛋白两两间均有一定的相关性(r=0.245~0.567,P<0.05)。结论:EGFR、Grb2、p-mTOR和VEGF表达与结直肠癌的发生、发展相关,值得进一步研究以作为结直肠癌肿瘤靶向治疗新的作用靶点。
关键词:  EGFR  Grb2  p-mTOR  VEGF  组织芯片  结直肠肿瘤
DOI:10.3724/SP.J.1008.2009.0775
投稿时间:2009-02-18修订日期:2009-06-19
基金项目:
Expression of EGFR,Grb2,p-mTOR and VEGF in human colorectal cancer tissues
XIANG Hong-gang,WANG Qiang*,HU Zhi-qian,XU Jian,WANG Wei-jun,WEI Zi-ran
(Department of General Surgery,Changzheng Hospital,Second Military Medical University,Shanghai 200003,China)
Abstract:
Objective:To observe the expression of phosphorylated mammalian target of rapamycin(p-mTOR),epidermal growth factor receptor(EGFR),growth factor receptor-bound protein 2(Grb2) and vascular endothelial growth factor(VEGF) in human colorectal cancer tissues and to explore their roles in the carcinogenesis of colorectal cancer.Methods: Tissue microarray containing 185 colorectal cancer tissues was constructed and the expression of EGFR,Grb2,p-mTOR and VEGF in the colorectal cancer tissues and the corresponding adjacent tissues was examined by immunohistochemistry methods.The relationship between their expression with the clinicopathological characteristics such as age,sex,invasion depth,lymphatic metastasis,clinical stage and differentiation degree was analyzed.Results: EGFR,Grb2,p-mTOR and VEGF were scarcely expressed or absent in the corresponding adjacent tissues; their positive rates in the colorectal caner tissues were 21.1%,44.9%,42.2% and 54.1%,respectively,which were significantly higher than those in the corresponding adjacent tissues(P<0.05). The expression of EGFR,Grb2,p-mTOR and VEGF was not correlated with the patients’ sex,age and differentiation degree of cancer.Over-expression of EGFR was found significantly associated with the invasion depth and clinical stage of cancer(P<0.05); and over-expression of p-mTOR and VEGF was significantly associated with lymphatic metastasis,invasion depth and clinical stage(P<0.05).There was a correlation between every two of the four proteins (r=0.245-0.567,P<0.05).Conclusion: Over-expression of EGFR,Grb2,p-mTOR and VEGF is closely associated with the development and progresssion of colorectal cancer,and they may be worth further studying as new targets for the molecular target therapy of colorectal cancer.
Key words:  EGFR  Grb2  p-mTOR  VEGF  tissue microarray  colorectal neoplasms