title: Discordance of Mutation Statuses of Epidermal Growth Factor Receptor and K-ras between Primary Adenocarcinoma of Lung and Brain Metastasis.
abstract: 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.
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung 833, Taiwan. kmrau58@adm.cgmh.org.tw.|Chang Gung Memorial Hospital, Kaohsiung, Taiwan and Chang Gung University College of Medicine, Tao-Yuan 333, Taiwan. kmrau58@adm.cgmh.org.tw.
authors.forename: Kun-Ming
authors.initials: KM
authors.lastname: Rau
authors.affiliation: Department of Pathology, Yuan's General Hospital, Kaohsiung 802, Taiwan. chenhanku@gmail.com.
authors.forename: Han-Ku
authors.initials: HK
authors.lastname: Chen
authors.affiliation: Biobank and Tissue Bank, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan. her2neu24@gmail.com.|Department of Medical Research, Cell Therapy and Research Center, E-Da Hospital, I-shou University, Kaohsiung 840, Taiwan. her2neu24@gmail.com.
authors.forename: Li-Yen
authors.initials: LY
authors.lastname: Shiu
authors.affiliation: Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan. tsaeling@cgmh.org.tw.
authors.forename: Tsai-Ling
authors.initials: TL
authors.lastname: Chao
authors.affiliation: Biobank and Tissue Bank, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan. monica0977@hotmail.com.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Lo
authors.affiliation: Chang Gung Memorial Hospital, Kaohsiung, Taiwan and Chang Gung University College of Medicine, Tao-Yuan 333, Taiwan. ccwang52@adm.cgmh.org.tw.|Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan. ccwang52@adm.cgmh.org.tw.
authors.forename: Chin-Chou
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Chang Gung Memorial Hospital, Kaohsiung, Taiwan and Chang Gung University College of Medicine, Tao-Yuan 333, Taiwan. mengchih@adm.cgmh.org.tw.|Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan. mengchih@adm.cgmh.org.tw.
authors.forename: Meng-Chih
authors.initials: MC
authors.lastname: Lin
authors.affiliation: Chang Gung Memorial Hospital, Kaohsiung, Taiwan and Chang Gung University College of Medicine, Tao-Yuan 333, Taiwan. huangcc@cgmh.org.tw.|Biobank and Tissue Bank and Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan. huangcc@cgmh.org.tw.
authors.forename: Chao-Cheng
authors.initials: CC
authors.lastname: Huang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)
keywords: EGFR mutation; K-ras mutation; adenocarcinoma of lung; brain metastasis; target therapy