Hepatocyte growth factor expression in EGFR mutant lung cancer with intrinsic and acquired resistance to tyrosine kinase inhibitors in a japanese cohort

Seiji Yano, Tadaaki Yamada, Shinji Takeuchi, Keisei Tachibana, Yuko Minami, Yasushi Yatabe, Tetsuya Mitsudomi, Hidenori Tanaka, Tatsuo Kimura, Shinzoh Kudoh, Hiroshi Nokihara, Yuichiro Ohe, Jun Yokota, Hidetaka Uramoto, Kosei Yasumoto, Katsuyuki Kiura, Masahiko Higashiyama, Makoto Oda, Haruhiro Saito, Junji YoshidaKazuya Kondoh, Masayuki Noguchi

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

Introduction: 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.

Original languageEnglish
Pages (from-to)2011-2017
Number of pages7
JournalJournal of Thoracic Oncology
Volume6
Issue number12
DOIs
Publication statusPublished - Dec 2011

Keywords

  • Acquired resistance
  • EGFR mutation
  • EGFR-TKI
  • HGF
  • Intrinsic resistance

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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    Yano, S., Yamada, T., Takeuchi, S., Tachibana, K., Minami, Y., Yatabe, Y., Mitsudomi, T., Tanaka, H., Kimura, T., Kudoh, S., Nokihara, H., Ohe, Y., Yokota, J., Uramoto, H., Yasumoto, K., Kiura, K., Higashiyama, M., Oda, M., Saito, H., ... Noguchi, M. (2011). Hepatocyte growth factor expression in EGFR mutant lung cancer with intrinsic and acquired resistance to tyrosine kinase inhibitors in a japanese cohort. Journal of Thoracic Oncology, 6(12), 2011-2017. https://doi.org/10.1097/JTO.0b013e31823ab0dd