Department of Pathology, Seoul National University Hospital, 28 Yeongeon-dong, Jongno-gu, Seoul 110-799, Korea.
Br J Cancer. 2012 Jul 10;107(2):325-33. doi: 10.1038/bjc.2012.237. Epub 2012 May 29.
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.
本研究旨在比较 MET 的基因拷贝数（GCN）和蛋白表达，并评估其在胃癌中的预后作用。
采用免疫组织化学（IHC）和银原位杂交（SISH）分别检测了大量胃癌中 MET 蛋白表达和基因扩增（GA）状态。
在 438 例病例中，有 104 例蛋白过表达，IHC 2+ 为 94 例，IHC 3+ 为 10 例，7 号染色体高倍体和 GA 分别为 61 例和 13 例。直接比较显示，蛋白高表达与 GCN 增加之间存在显著相关性。所有 GA 病例均显示蛋白过表达。此外，除 1 例外，所有 IHC 3+病例均存在 GA，即使根据 ASCO/CAP 人表皮生长因子受体 2 评估指南，该病例也可归类为 GA。IHC 3+和 GA 与预后不良显著相关。
MET IHC 很好地反映了 GA，因此，如果 GA 是药物反应性的主要决定因素，那么它可以作为抗-MET 治疗患者选择的初步筛选试验。此外，MET 的预后作用表明，抗-MET 治疗是胃癌辅助治疗中一种很有前途的治疗方式。
