title: Hepatocyte growth factor expression in EGFR mutant lung cancer with intrinsic and acquired resistance to tyrosine kinase inhibitors in a Japanese cohort.
abstract: BACKGROUND
  This study was performed to determine the incidence rates of resistance factors, i.e., high-level hepatocyte growth factor (HGF) expression, epidermal growth factor receptor (EGFR) T790M secondary mutation, and MET amplification, in tumors with intrinsic and acquired EGFR tyrosine kinase inhibitor (TKI) resistance in EGFR mutant lung cancer.
  
  
  METHODS
  Ninety-seven specimens from 93 EGFR mutant lung cancer patients (23 tumors with acquired resistance from 20 patients, 45 tumors with intrinsic resistance from 44 patients [nonresponders], 29 sensitive tumors from 29 patients) from 11 institutes in Japan were analyzed. HGF expression, EGFR T790M secondary mutation, and MET amplification were determined by immunohistochemistry, cycleave real-time polymerase chain reaction, and fluorescence in situ hybridization, respectively.
  
  
  RESULTS
  High-level HGF expression, EGFR T790M secondary mutation, and MET amplification were detected in 61, 52, and 9% of tumors with acquired resistance, respectively. High-level HGF expression was detected in 29% of tumors with intrinsic resistance (nonresponders), whereas EGFR T790M secondary mutation and MET amplification were detected in 0 and 4%, respectively. HGF expression was significantly higher in tumors with acquired resistance than in sensitive tumors (p < 0.001, Student's t test). Fifty percent of tumors with acquired resistance showed simultaneous HGF expression with EGFR T790M secondary mutation and MET amplification.
  
  
  CONCLUSIONS
  High-level HGF expression was detected more frequently than EGFR T790M secondary mutation or MET amplification in tumors with intrinsic and acquired EGFR-TKI resistance in EGFR mutant lung cancer in Japanese patients. These observations provide a rationale for targeting HGF in EGFR-TKI resistance in EGFR mutant lung cancer.
authors: Division of Medical Oncology, Cancer Research Institute, Kanazawa University, Takara-machi, Kanazawa, Japan. syano@staff.kanazawa-u.ac.jp
authors: Seiji
authors: S
authors: Yano
authors: Tadaaki
authors: T
authors: Yamada
authors: Shinji
authors: S
authors: Takeuchi
authors: Keisei
authors: K
authors: Tachibana
authors: Yuko
authors: Y
authors: Minami
authors: Yasushi
authors: Y
authors: Yatabe
authors: Tetsuya
authors: T
authors: Mitsudomi
authors: Hidenori
authors: H
authors: Tanaka
authors: Tatsuo
authors: T
authors: Kimura
authors: Shinzoh
authors: S
authors: Kudoh
authors: Hiroshi
authors: H
authors: Nokihara
authors: Yuichiro
authors: Y
authors: Ohe
authors: Jun
authors: J
authors: Yokota
authors: Hidetaka
authors: H
authors: Uramoto
authors: Kosei
authors: K
authors: Yasumoto
authors: Katsuyuki
authors: K
authors: Kiura
authors: Masahiko
authors: M
authors: Higashiyama
authors: Makoto
authors: M
authors: Oda
authors: Haruhiro
authors: H
authors: Saito
authors: Junji
authors: J
authors: Yoshida
authors: Kazuya
authors: K
authors: Kondoh
authors: Masayuki
authors: M
authors: Noguchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D005784:Gene Amplification; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D011799:Quinazolines / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D017228:Hepatocyte Growth Factor; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met; D000077156:Gefitinib