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

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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

Fingerprint

Hepatocyte Growth Factor
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Lung Neoplasms
Neoplasms
Mutation
R Factors
Fluorescence In Situ Hybridization
Real-Time Polymerase Chain Reaction
Japan

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Hepatocyte growth factor expression in EGFR mutant lung cancer with intrinsic and acquired resistance to tyrosine kinase inhibitors in a japanese cohort. / Yano, Seiji; Yamada, Tadaaki; Takeuchi, Shinji; Tachibana, Keisei; Minami, Yuko; Yatabe, Yasushi; Mitsudomi, Tetsuya; Tanaka, Hidenori; Kimura, Tatsuo; Kudoh, Shinzoh; Nokihara, Hiroshi; Ohe, Yuichiro; Yokota, Jun; Uramoto, Hidetaka; Yasumoto, Kosei; Kiura, Katsuyuki; Higashiyama, Masahiko; Oda, Makoto; Saito, Haruhiro; Yoshida, Junji; Kondoh, Kazuya; Noguchi, Masayuki.

In: Journal of Thoracic Oncology, Vol. 6, No. 12, 12.2011, p. 2011-2017.

Research output: Contribution to journalArticle

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, Yoshida, J, Kondoh, K & 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, vol. 6, no. 12, pp. 2011-2017. https://doi.org/10.1097/JTO.0b013e31823ab0dd
Yano, Seiji ; Yamada, Tadaaki ; Takeuchi, Shinji ; Tachibana, Keisei ; Minami, Yuko ; Yatabe, Yasushi ; Mitsudomi, Tetsuya ; Tanaka, Hidenori ; Kimura, Tatsuo ; Kudoh, Shinzoh ; Nokihara, Hiroshi ; Ohe, Yuichiro ; Yokota, Jun ; Uramoto, Hidetaka ; Yasumoto, Kosei ; Kiura, Katsuyuki ; Higashiyama, Masahiko ; Oda, Makoto ; Saito, Haruhiro ; Yoshida, Junji ; Kondoh, Kazuya ; Noguchi, Masayuki. / Hepatocyte growth factor expression in EGFR mutant lung cancer with intrinsic and acquired resistance to tyrosine kinase inhibitors in a japanese cohort. In: Journal of Thoracic Oncology. 2011 ; Vol. 6, No. 12. pp. 2011-2017.
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T1 - Hepatocyte growth factor expression in EGFR mutant lung cancer with intrinsic and acquired resistance to tyrosine kinase inhibitors in a japanese cohort

AU - Yano, Seiji

AU - Yamada, Tadaaki

AU - Takeuchi, Shinji

AU - Tachibana, Keisei

AU - Minami, Yuko

AU - Yatabe, Yasushi

AU - Mitsudomi, Tetsuya

AU - Tanaka, Hidenori

AU - Kimura, Tatsuo

AU - Kudoh, Shinzoh

AU - Nokihara, Hiroshi

AU - Ohe, Yuichiro

AU - Yokota, Jun

AU - Uramoto, Hidetaka

AU - Yasumoto, Kosei

AU - Kiura, Katsuyuki

AU - Higashiyama, Masahiko

AU - Oda, Makoto

AU - Saito, Haruhiro

AU - Yoshida, Junji

AU - Kondoh, Kazuya

AU - Noguchi, Masayuki

PY - 2011/12

Y1 - 2011/12

N2 - 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.

AB - 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.

KW - Acquired resistance

KW - EGFR mutation

KW - EGFR-TKI

KW - HGF

KW - Intrinsic resistance

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