University of Chicago, Department of Pathology, Chicago, Illinois 60637, USA.
J Environ Pathol Toxicol Oncol. 2011;30(4):341-54. doi: 10.1615/jenvironpatholtoxicoloncol.v30.i4.70.
This study aimed to investigate the expression and prognostic role of the receptor tyrosine kinase MET, phosphorylated MET, and the ligand hepatocyte growth factor (HGF) in patients with lung cancer. This retrospective study included 129 patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) with available tumor tissue and survival data. MET, pMET, and HGF expression were assessed using immunohistochemistry. MET, pMET, and HGF were more highly expressed in tumor tissue when compared to the adjacent lung parenchyma. A specific localization pattern was also evident: membranous, cytoplasmic, and nuclear patterns of expression were seen for MET, pMET, and HGF. In addition, high expression of two specific forms of phosphorylated MET--cytoplasmic expression of Y1003 and nuclear expression of Y1365--appeared to correlate with a worse overall survival (P = .016; hazard ratio [HR], 1.86; 95% confidence interval [95% CI], 1.12- 3.07; and P = .034; HR, 1.70; 95% CI, 1.04-2.78, respectively). In summary, MET, pMET, and HGF are highly expressed in both NSCLC and SCLC. Specific forms of pMET may serve as potential biomarkers in lung cancer.
本研究旨在探讨受体酪氨酸激酶 MET、磷酸化 MET 及其配体肝细胞生长因子(HGF)在肺癌患者中的表达及其预后作用。这项回顾性研究纳入了 129 例有肿瘤组织和生存数据的非小细胞肺癌(NSCLC)和小细胞肺癌(SCLC)患者。采用免疫组织化学法检测 MET、pMET 和 HGF 的表达。与相邻肺实质相比,肿瘤组织中 MET、pMET 和 HGF 的表达更高。还观察到特定的定位模式:MET、pMET 和 HGF 的表达呈现膜性、细胞质性和核性模式。此外,两种特定形式的磷酸化 MET——细胞质表达的 Y1003 和核表达的 Y1365——的高表达似乎与总体生存较差相关(P =.016;危险比 [HR],1.86;95%置信区间 [95%CI],1.12-3.07;和 P =.034;HR,1.70;95%CI,1.04-2.78)。总之,MET、pMET 和 HGF 在 NSCLC 和 SCLC 中均高度表达。特定形式的 pMET 可能成为肺癌的潜在生物标志物。