Rau Kun-Ming, Chen Han-Ku, Shiu Li-Yen, Chao Tsai-Ling, Lo Yi-Ping, Wang Chin-Chou, Lin Meng-Chih, Huang Chao-Cheng
Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung 833, Taiwan.
Chang Gung Memorial Hospital, Kaohsiung, Taiwan and Chang Gung University College of Medicine, Tao-Yuan 333, Taiwan.
Int J Mol Sci. 2016 Apr 7;17(4):524. doi: 10.3390/ijms17040524.
Mutations on epidermal growth factor receptor (EGFR) of adenocarcinomas of lung have been found to be associated with increased sensitivity to EGFR tyrosine kinase inhibitors and K-ras mutations may correlate with primary resistance. We aimed to explore the discordant mutation statuses of EGFR and K-ras between primary tumors and matched brain metastases in adenocarcinomas of lung. We used a sensitive Scorpion ARMS method to analyze EGFR mutation, and Sanger sequencing followed by allele-specific real-time polymerase chain reaction to analyze K-ras mutation. Forty-nine paired tissues with both primary adenocarcinoma of lung and matched brain metastasis were collected. Thirteen patients (26.5%) were discordant for the status of EGFR between primary and metastatic sites. K-ras gene could be checked in paired specimens from 33 patients, thirteen patients (39.6%) were discordant for the status of K-ras. In primary lung adenocarcinoma, there were 14 patients of mutant EGFR had mutant K-ras synchronously. This study revealed that the status of EGFR mutation in lung adenocarcinomas is relatively consistent between primary and metastatic sites compared to K-ras mutation. However, there are still a few cases of adenocarcinoma of lung showing discordance for the status of EGFR mutation. Repeated analysis of EGFR mutation is highly recommended if tissue from metastatic or recurrent site is available for the evaluation of target therapy.
已发现肺腺癌表皮生长因子受体(EGFR)突变与对EGFR酪氨酸激酶抑制剂的敏感性增加相关,而K-ras突变可能与原发性耐药相关。我们旨在探讨肺腺癌原发性肿瘤与配对脑转移瘤之间EGFR和K-ras的不一致突变状态。我们使用灵敏的Scorpion ARMS方法分析EGFR突变,并采用桑格测序法随后进行等位基因特异性实时聚合酶链反应分析K-ras突变。收集了49对同时含有原发性肺腺癌和配对脑转移瘤的组织。13例患者(26.5%)的原发性和转移部位之间EGFR状态不一致。对33例患者的配对标本可检测K-ras基因,13例患者(39.6%)的K-ras状态不一致。在原发性肺腺癌中,有14例EGFR突变患者同时伴有K-ras突变。本研究表明,与K-ras突变相比,肺腺癌原发性和转移部位之间EGFR突变状态相对一致。然而,仍有少数肺腺癌病例EGFR突变状态不一致。如果有转移或复发部位的组织可用于评估靶向治疗,强烈建议重复分析EGFR突变。