MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas
MET overexpression assessed by new interpretation method predicts gene amplification and poor survival in advanced gastric carcinomas
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DOI：
10.1038/modpathol.2013.108
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发表时间：
2013-12-01
期刊：
影响因子：
7.5
通讯作者：
Kim, Kyoung-Mee
中科院分区：
文献类型：
--
作者：
Ha, Sang Y.;Lee, Jeeyun;Kim, Kyoung-Mee
建立更好的选择标准来识别可能受益于治疗的亚群是靶向治疗发展和成功的一个关键方面。为了研究评估胃癌中 MET 过表达的方法，我们使用新型抗总 MET 单克隆抗体对 495 名患者的单机构队列进行了免疫组织化学分析。由于抗体针对膜和/或细胞质表位，因此使用两种解释方法：(1)膜和细胞质和(2)单独的膜。在选定的 120 个病例中，使用定量实时 PCR 测量了拷贝数增益和 mRNA 表达水平。进一步的原位杂交证实了MET基因扩增的存在。在495例胃癌中，MET膜和细胞质同时过表达108例（21.8%），膜单独过表达40例（8.1%）。在 MET 的膜和细胞质染色中观察到最高相关性：MET 表达评分与高 MET mRNA 水平显着相关（r=0.465，P
The establishment of better selection criteria for identifying sub-populations that may benefit from treatment is a key aspect of the development and success of targeted therapy. To investigate methods for assessing MET overexpression in gastric cancer, we conducted immunohistochemistry using a new anti-Total MET monoclonal antibody in a single-institution cohort of 495 patients. As antibody is directed against a membranous and/or cytoplasmic epitope, two interpretation methods were used: (1) membranous and cytoplasmic and (2) membranous alone. In selected 120 cases, copy number gain and mRNA expression levels were measured using quantitative real-time PCR. Further in situ hybridization confirmed the presence of MET gene amplification. Among the 495 gastric cancers, simultaneous membranous and cytoplasmic overexpression of MET was found in 108 cases (21.8%) and membranous alone overexpression was observed in 40 cases (8.1%). The highest correlation was observed in membranous and cytoplasmic staining of MET: MET expression scores correlated significantly with high MET mRNA levels (r=0.465, P