MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome.

MET in gastric carcinomas: comparison between protein expression and gene copy number and impact on clinical outcome.
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DOI:
10.1038/bjc.2012.237
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发表时间:
2012-07-10
影响因子:
8.8
通讯作者:
Kim, W. H.
Kim, W. H.
中科院分区:
医学1区
文献类型:
--
作者:
Lee, H. E.;Kim, M. A.;Lee, H. S.;Jung, E-J;Yang, H-K;Lee, B. L.;Bang, Y-J;Kim, W. H.

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本研究的目的是比较MET基因拷贝数(GCN)和蛋白表达,并评估其在胃癌预后中的作用。MET蛋白表达和基因扩增(GA)的状态分别通过免疫组织化学(IHC)和银原位杂交(SISH),在一个大系列的胃癌。438例中有104例蛋白过度表达,其中94例为IHC 2+,10例为IHC 3+,381例中分别有61例和13例发现7号染色体和GA高度多体性。直接比较显示高水平的蛋白表达和GCN增加之间存在显著相关性。所有GA病例均表现为蛋白过度表达。此外,除1外,所有免疫组化3+均显示GA,即使根据ASCO/CAP人类表皮生长因子受体2评估指南,其也可归类为GA。IHC 3+和GA与不良预后显著相关。MET IHC在GA上反映良好,因此,如果GA是药物反应性的主要决定因素,则其可以作为抗MET治疗患者选择的主要筛选试验。此外,MET的预后作用表明,抗MET治疗是一种非常有前途的胃癌辅助治疗方式。
The aim of this study was to compare gene copy number (GCN) and protein expression of MET and to evaluate their prognostic roles in gastric carcinomas. MET protein expression and gene amplification (GA) status were determined by immunohistochemistry (IHC) and silver in-situ hybridisation (SISH), respectively, in a large series of gastric carcinoma. Protein overexpression was observed in 104 of 438 cases, with IHC 2+ in 94 and IHC 3+ in 10, and high polysomy of chromosome 7 and GA were found in 61 and 13 of 381, respectively. Direct comparison revealed a significant correlation between high level of protein expression and increased GCN. All cases with GA showed protein overexpression. Furthermore, all with IHC 3+ showed GA except 1, even which could be categorised as GA according to the ASCO/CAP guideline for human epidermal growth factor receptor 2 assessment. IHC 3+ and GA were significantly associated with poor prognosis. MET IHC reflects well on GA, and therefore, it could be a primary screening test for patient selection for anti-MET therapy if GA is a major determinant of drug responsiveness. Also, the prognostic role of MET indicates that anti-MET therapy is a very promising modality in adjuvant treatment for gastric cancer.
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