全面的分子分析肺腺癌表皮生长因子受体、K-ras、MET 和肝细胞生长因子的状态。
Comprehensive molecular analyses of lung adenocarcinoma with regard to the epidermal growth factor receptor, K-ras, MET, and hepatocyte growth factor status.
机构信息
Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
出版信息
J Thorac Oncol. 2010 May;5(5):591-6. doi: 10.1097/JTO.0b013e3181d0a4db.
BACKGROUND
The mutation and amplification of oncogenic genes are associated with carcinogenesis and tumor growth. The purpose of this study was to clarify the role of the epidermal growth factor receptor (EGFR), K-ras, MET, and hepatocyte growth factor (HGF) status in lung adenocarcinoma.
METHODS
Tumor specimens were collected from 183 patients who underwent a complete resection for adenocarcinoma of the lung from 2003 to 2007 in our department. The genetic status of the EGFR and K-ras genes were investigated by polymerase chain reaction (PCR)-based analyses. Immunohistochemistry and real time PCR assays were used to evaluate the MET gene regarding to tyrosine phosphorylation and amplification, respectively. HGF status was evaluated by immunohistochemistry.
RESULTS
The mutations of EGFR and K-ras were detected in 64 (35%) and 17 patients (9%), respectively. The tyrosine 1234/1235 phosphorylation of MET (p-MET 1234/1235) and MET amplification was identified in 12 (7%) and 8 (4%) specimens, respectively. Positive expression of HGF was identified in 104 specimens (57%). An EGFR mutation was found significantly more frequently in females and in tumors with wild type of K-ras and without MET amplification. A p-MET 1234/1235 was found significantly more frequently in the tumors with a positive expression of HGF. A multivariate survival analysis demonstrated that the wild type of K-ras, negative p-MET 1234/1235, and positive HGF expression were independently associated with an increased risk of poor survival.
CONCLUSIONS
The occurrence of MET amplification and EGFR/ K-ras mutations might be mutually exclusive suggesting several distinct mechanisms in the development of lung adenocarcinoma. The wild type of K-ras, negative p-MET 1234/1235, and positive expression of HGF may be a useful marker for predicting poor prognosis of patients who underwent surgical resection of lung adenocarcinoma.
背景
致癌基因的突变和扩增与癌症发生和肿瘤生长有关。本研究旨在阐明表皮生长因子受体（EGFR）、K-ras、MET 和肝细胞生长因子（HGF）状态在肺腺癌中的作用。
方法
收集 2003 年至 2007 年我科行肺腺癌完全切除术的 183 例患者的肿瘤标本。采用聚合酶链反应（PCR）技术分析 EGFR 和 K-ras 基因的遗传状态。采用免疫组织化学和实时 PCR 检测 MET 基因的酪氨酸磷酸化和扩增。采用免疫组织化学检测 HGF 状态。
结果
EGFR 和 K-ras 突变分别在 64 例（35%）和 17 例（9%）患者中检出。MET 酪氨酸 1234/1235 磷酸化（p-MET 1234/1235）和 MET 扩增分别在 12 例（7%）和 8 例（4%）标本中检出。HGF 阳性表达在 104 例标本（57%）中检出。EGFR 突变在女性和 K-ras 野生型且无 MET 扩增的肿瘤中更常见。p-MET 1234/1235 在 HGF 阳性表达的肿瘤中更常见。多因素生存分析表明，K-ras 野生型、p-MET 1234/1235 阴性和 HGF 阳性表达与生存不良风险增加独立相关。
结论
MET 扩增和 EGFR/K-ras 突变的发生可能相互排斥，提示肺腺癌的发生存在几种不同的机制。K-ras 野生型、p-MET 1234/1235 阴性和 HGF 阳性表达可能是预测肺腺癌患者手术切除后不良预后的有用标志物。
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