Hepatocyte Growth Factor Expression in EGFR Mutant Lung Cancer with Intrinsic and Acquired Resistance to Tyrosine Kinase Inhibitors in a Japanese Cohort

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 (...

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Bibliographic Details
Published in:Journal of thoracic oncology 2011-12, Vol.6 (12), p.2011-2017
Main Authors: 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
Format: Article
Language:English
Subjects:
Acquired resistance
Adult
Aged
Aged, 80 and over
Carcinoma - drug therapy
Carcinoma - genetics
Drug Resistance, Neoplasm - genetics
EGFR mutation
EGFR-TKI
Erlotinib Hydrochloride
Gene Amplification
Hepatocyte Growth Factor - genetics
HGF
Humans
Intrinsic resistance
Japan
Lung Neoplasms - drug therapy
Lung Neoplasms - genetics
Male
Middle Aged
Mutation
Protein Kinase Inhibitors - therapeutic use
Proto-Oncogene Proteins c-met - genetics
Quinazolines - therapeutic use
Receptor, Epidermal Growth Factor - genetics
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Summary: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. 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. 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. 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.
ISSN:1556-0864
1556-1380
DOI:10.1097/JTO.0b013e31823ab0dd