Molecular changes of epidermal growth factor receptor (EGFR) and KRAS and their impact on the clinical outcomes in surgically resected adenocarcinoma of the lung
Molecular changes of epidermal growth factor receptor (EGFR) and KRAS and their impact on the clinical outcomes in surgically resected adenocarcinoma of the lung
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DOI：
10.1016/j.lungcan.2007.08.008
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发表时间：
2008-01-01
期刊：
影响因子：
5.3
通讯作者：
Kim, Joo Hyun
中科院分区：
文献类型：
--
作者：
Kim, Young Tae;Kim, Tae-you;Kim, Joo Hyun
近年来研究发现，晚期肺癌患者对表皮生长因子受体（EGFR）抑制剂的临床反应与EGFR的体细胞变化有关。然而，EGFR本身的这种分子变化是否会影响手术切除后早期癌症的临床结局，目前尚无明确的数据。我们对71例接受手术切除的腺癌患者进行了EGFR和KRAS基因突变的研究。应用荧光原位杂交（FISH）技术对48例患者进行EGFR基因扩增，发现25例（35.2%）患者存在EGFR突变。EGFR突变在具有BAC特征的病例（13/22（59.1%）：13/49（26.5%）; p=0.008）和非吸烟者（19/41（46.3%）：7/30（23.3%）; p=0.047）中更常见。然而，EGFR突变与年龄、性别或临床分期无关。EGFR拷贝扩增在女性（12/29（41.4%）：3/19（15.8%）; p=0.061）和晚期（≥ IIIA期，9/19（47.4%）：6/29（20.7%）; p = 0.051）中经常观察到。5例患者（7.0%）存在KRAS突变，无一例显示EGFR突变。KRAS突变（p=0.000），交配性别（p=0.001），无BAC特征（p=0.003），晚期（p=0.039），吸烟史（p=0.030）是总生存率的不良预后因素，而EGFR突变（p=0.184）和扩增EGFR突变的存在不是手术切除后早期肺癌临床结果的预后因素。这一结果为EGFR抑制剂在早期肺癌中的未来试验方案设计提供了重要信息。由于KRAS基因突变是一个预后不良的因素，且与EGFR基因突变密切相关，因此在此类试验中应研究KRAS基因突变。而KRAS突变是一个预后不良的因素，EGFR突变不是，其本身的存在并不影响手术切除后的早期肺癌的临床结果。(c)2007爱思唯尔爱尔兰有限公司保留所有权利。
Recent studies have reported that clinical response to epidermal growth factor receptor (EGFR) inhibitors is associated with somatic changes of EGFR in the advanced stage of lung cancer. However, there is no clear data demonstrating whether such molecular changes of EGFR per se can affect the clinical outcome of early stage cancer after surgical resection.DNA mutations of EGFR and KRAS were investigated in 71 adenocarcinoma patients who received surgical resection. Fluorescence in situ hybridization (FISH) of EGFR gene amplification was performed in 48 samples.We detected EGFR mutations in 25 patients (35.2%). EGFR mutation was more frequently found in cases with BAC features (13/22 (59.1%):13/49 (26.5%); p=0.008) and in non-smokers (19/41 (46.3%):7/30 (23.3%); p=0.047). However, the EGFR mutation was not associated with age, gender, or clinical stage. The amplification of EGFR copy was frequently observed in the female gender (12/29 (41.4%):3/19 (15.8%); p=0.061) and in the advanced stage (>= Stage IIIA, 9/19 (47.4%):6/29 (20.7%); p = 0.051). KRAS mutations were present in five patients (7.0%) and none of them showed EGFR mutation. KRAS mutations (p=0.000), mate gender (p=0.001), absence of BAC feature (p=0.003), advanced stage (p=0.039), and smoking history (p=0.030) were poor prognostic factors for overall survival, whereas EGFR mutation (p=0.184) and amplification (p=0.756) were not.The presence of EGFR mutation was not a prognostic factor of the clinical outcome of early lung cancer after surgical resection. This result provides an important message for the protocol design of future trials of EGFR inhibitors in early lung cancer. As the KRAS mutation was a poor prognostic factor and it presents reciprocally with EGFR mutation, KRAS mutation should be investigated in such trials.DNA mutations of EGFR and KRAS were investigated in 71 adenocarcinoma patients who received surgical resection. Whereas KRAS mutation was a poor prognostic factor, EGFR mutation was not, and its presence per se did not affect the clinical outcome of early lung cancer after surgical resection. (c) 2007 Elsevier Ireland Ltd. All rights reserved.