Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, NY 10065, USA.
Cancer Epidemiol Biomarkers Prev. 2011 May;20(5):1021-7. doi: 10.1158/1055-9965.EPI-10-1080. Epub 2011 Mar 10.
MET, the receptor for hepatocyte growth factor, has been proposed as a therapeutic target in gastric cancer. This study assessed the incidence of MET expression and gene amplification in tumors of Western patients with gastric cancer.
Tumor specimens from patients enrolled on a preoperative chemotherapy study (NCI 5700) were examined for the presence of MET gene amplification by FISH, MET mRNA expression by quantitative PCR, MET overexpression by immunohistochemistry (IHC), and for evidence of MET pathway activation by phospho-MET (p-MET) IHC.
Although high levels of MET protein and mRNA were commonly encountered (in 63% and 50% of resected tumor specimens, respectively), none of these tumors had MET gene amplification by FISH, and only 6.6% had evidence of MET tyrosine kinase activity by p-MET IHC.
In this cohort of patients with localized gastric cancer, the presence of high MET protein and RNA expression does not correlate with MET gene amplification or pathway activation, as evidenced by the absence of amplification by FISH and negative p-MET IHC analysis.
This article shows a lack of MET amplification and pathway activation in a cohort of 38 patients with localized gastric cancer, suggesting that MET-driven gastric cancers are relatively rare in Western patients.
肝细胞生长因子的受体 MET 已被提议作为胃癌的治疗靶点。本研究评估了西方胃癌患者肿瘤中 MET 表达和基因扩增的发生率。
通过荧光原位杂交 (FISH) 检测 NCI 5700 术前化疗研究入组患者的肿瘤标本中 MET 基因扩增情况，通过定量 PCR 检测 MET mRNA 表达，通过免疫组化 (IHC) 检测 MET 过表达，并通过磷酸化 MET (p-MET) IHC 检测 MET 通路激活的证据。
尽管经常遇到高水平的 MET 蛋白和 mRNA（分别在 63%和 50%的切除肿瘤标本中），但这些肿瘤中没有 FISH 检测到 MET 基因扩增，只有 6.6%的肿瘤通过 p-MET IHC 检测到 MET 酪氨酸激酶活性。
在这组局部胃癌患者中，高 MET 蛋白和 RNA 表达与 MET 基因扩增或通路激活无关，这一点从 FISH 检测未见扩增和 p-MET IHC 分析阴性可以证明。
本文显示了 38 例局部胃癌患者中缺乏 MET 扩增和通路激活，表明在西方患者中，由 MET 驱动的胃癌相对较少。
