Comprehensive Molecular Analyses of Lung Adenocarcinoma with Regard to the Epidermal Growth Factor Receptor, K-ras, MET, and Hepatocyte Growth Factor Status
Comprehensive Molecular Analyses of Lung Adenocarcinoma with Regard to the Epidermal Growth Factor Receptor, K-ras, MET, and Hepatocyte Growth Factor Status
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DOI：
10.1097/jto.0b013e3181d0a4db
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发表时间：
2010-05-01
影响因子：
20.4
通讯作者：
Yasumoto, Kosei
中科院分区：
文献类型：
--
作者：
Onitsuka, Takamitsu;Uramoto, Hidetaka;Yasumoto, Kosei
背景：癌基因的突变和扩增与肿瘤的发生、发展密切相关。本研究的目的是阐明表皮生长因子受体（EGFR），K-ras，MET和肝细胞生长因子（HGF）的状态在肺adenocarcino.Methods：肿瘤标本收集自2003年至2007年在我科的183例肺腺癌行完整切除术的患者。EGFR和K-ras基因的遗传状态通过聚合酶链反应（PCR）为基础的分析进行了研究。免疫组化和真实的时间PCR检测分别用于评估MET基因的酪氨酸磷酸化和扩增。结果：EGFR和K-ras基因突变分别为64例（35%）和17例（9%）。分别在12份（7%）和8份（4%）标本中发现MET的酪氨酸1234/1235磷酸化（p-MET 1234/1235）和MET扩增。104例（57%）肝细胞生长因子阳性表达。EGFR突变在女性和具有野生型K-ras且无MET扩增的肿瘤中显著更常见。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，野生型K-ras，阴性p-MET 1234/1235，和阳性HGF表达独立与生存不良的风险增加。结论：MET扩增和EGFR/K-ras突变的发生可能是相互排斥的，提示在肺腺癌的发展中有几个不同的机制。K-ras野生型、p-MET 1234/1235阴性、HGF阳性表达可能是肺腺癌手术切除后预后不良的一个有用指标。
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.