The influence of intracellular epidermal growth factor receptor (EGFR) signal activation on the outcome of EGFR tyrosine kinase inhibitor treatment for pulmonary adenocarcinoma

Daigo Kawano, Tokujiro Yano, Fumihiro Shoji, Kensaku Ito, Yosuke Morodomi, Akira Haro, Naoko Miura, Tomoyoshi Takenaka, Ichiro Yoshino, Yoshihiko Maehara

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Purpose: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, exhibit up to a 70% response rate against non-small cell lung cancer (NSCLC) harboring somatic activating mutations of the EGFR gene (EGFR). The mechanism of intrinsic resistance of EGFR mutation-positive NSCLC against EGFR-TKIs is not known. The current study assesses the relationship between the molecular expression of EGFR signals and the response to gefitinib treatment in patients with pulmonary adenocarcinoma to elucidate the mechanism of intrinsic resistance to gefitinib. Methods: The present study included 30 patients with pulmonary adenocarcinoma who were treated with gefitinib for a postoperative recurrence. The correlation between the response to gefitinib treatment and various clinical and molecular features was evaluated. Results: EGFR mutations were detected in 20 (66.7%) of the 30 patients. The response to gefitinib treatment was a complete response in 1 case, partial response in 12 cases, stable disease in 4 cases, and progressive disease in 13 cases. Both univariate and multivariate analyses showed the presence of an EGFR mutation, and the expression of phospho-EGFR (p-EGFR) significantly correlated with a better response to gefitinib treatment. Ten of the 16 p-EGFR positive patients were disease controlled, but all 4 p-EGFR negative patients were intrinsically resistant to EGFR-TKIs (P = 0.025). Other factors including sex, smoking status, serum carcinoembryonic antigen and cytokeratin-19 fragment levels, EGFR, Met proto-oncogene, phospho-Met, and hepatocyte growth factor expression were not associated with the response to gefitinib treatment. Conclusion: These results suggest that, even if EGFR mutations were observed, a p-EGFR negative state might be a cause of intrinsic resistance to EGFR-TKIs.

Original languageEnglish
Pages (from-to)818-823
Number of pages6
JournalSurgery today
Volume41
Issue number6
DOIs
Publication statusPublished - Jun 1 2011

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Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Therapeutics
Mutation
Non-Small Cell Lung Carcinoma
Adenocarcinoma of lung
Keratin-19
erbB-1 Genes
Sex Factors
Hepatocyte Growth Factor
Proto-Oncogenes
gefitinib
Carcinoembryonic Antigen
Multivariate Analysis
Smoking
Recurrence

All Science Journal Classification (ASJC) codes

  • Surgery

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The influence of intracellular epidermal growth factor receptor (EGFR) signal activation on the outcome of EGFR tyrosine kinase inhibitor treatment for pulmonary adenocarcinoma. / Kawano, Daigo; Yano, Tokujiro; Shoji, Fumihiro; Ito, Kensaku; Morodomi, Yosuke; Haro, Akira; Miura, Naoko; Takenaka, Tomoyoshi; Yoshino, Ichiro; Maehara, Yoshihiko.

In: Surgery today, Vol. 41, No. 6, 01.06.2011, p. 818-823.

Research output: Contribution to journalArticle

Kawano, Daigo ; Yano, Tokujiro ; Shoji, Fumihiro ; Ito, Kensaku ; Morodomi, Yosuke ; Haro, Akira ; Miura, Naoko ; Takenaka, Tomoyoshi ; Yoshino, Ichiro ; Maehara, Yoshihiko. / The influence of intracellular epidermal growth factor receptor (EGFR) signal activation on the outcome of EGFR tyrosine kinase inhibitor treatment for pulmonary adenocarcinoma. In: Surgery today. 2011 ; Vol. 41, No. 6. pp. 818-823.
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AU - Kawano, Daigo

AU - Yano, Tokujiro

AU - Shoji, Fumihiro

AU - Ito, Kensaku

AU - Morodomi, Yosuke

AU - Haro, Akira

AU - Miura, Naoko

AU - Takenaka, Tomoyoshi

AU - Yoshino, Ichiro

AU - Maehara, Yoshihiko

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N2 - Purpose: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, exhibit up to a 70% response rate against non-small cell lung cancer (NSCLC) harboring somatic activating mutations of the EGFR gene (EGFR). The mechanism of intrinsic resistance of EGFR mutation-positive NSCLC against EGFR-TKIs is not known. The current study assesses the relationship between the molecular expression of EGFR signals and the response to gefitinib treatment in patients with pulmonary adenocarcinoma to elucidate the mechanism of intrinsic resistance to gefitinib. Methods: The present study included 30 patients with pulmonary adenocarcinoma who were treated with gefitinib for a postoperative recurrence. The correlation between the response to gefitinib treatment and various clinical and molecular features was evaluated. Results: EGFR mutations were detected in 20 (66.7%) of the 30 patients. The response to gefitinib treatment was a complete response in 1 case, partial response in 12 cases, stable disease in 4 cases, and progressive disease in 13 cases. Both univariate and multivariate analyses showed the presence of an EGFR mutation, and the expression of phospho-EGFR (p-EGFR) significantly correlated with a better response to gefitinib treatment. Ten of the 16 p-EGFR positive patients were disease controlled, but all 4 p-EGFR negative patients were intrinsically resistant to EGFR-TKIs (P = 0.025). Other factors including sex, smoking status, serum carcinoembryonic antigen and cytokeratin-19 fragment levels, EGFR, Met proto-oncogene, phospho-Met, and hepatocyte growth factor expression were not associated with the response to gefitinib treatment. Conclusion: These results suggest that, even if EGFR mutations were observed, a p-EGFR negative state might be a cause of intrinsic resistance to EGFR-TKIs.

AB - Purpose: The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, exhibit up to a 70% response rate against non-small cell lung cancer (NSCLC) harboring somatic activating mutations of the EGFR gene (EGFR). The mechanism of intrinsic resistance of EGFR mutation-positive NSCLC against EGFR-TKIs is not known. The current study assesses the relationship between the molecular expression of EGFR signals and the response to gefitinib treatment in patients with pulmonary adenocarcinoma to elucidate the mechanism of intrinsic resistance to gefitinib. Methods: The present study included 30 patients with pulmonary adenocarcinoma who were treated with gefitinib for a postoperative recurrence. The correlation between the response to gefitinib treatment and various clinical and molecular features was evaluated. Results: EGFR mutations were detected in 20 (66.7%) of the 30 patients. The response to gefitinib treatment was a complete response in 1 case, partial response in 12 cases, stable disease in 4 cases, and progressive disease in 13 cases. Both univariate and multivariate analyses showed the presence of an EGFR mutation, and the expression of phospho-EGFR (p-EGFR) significantly correlated with a better response to gefitinib treatment. Ten of the 16 p-EGFR positive patients were disease controlled, but all 4 p-EGFR negative patients were intrinsically resistant to EGFR-TKIs (P = 0.025). Other factors including sex, smoking status, serum carcinoembryonic antigen and cytokeratin-19 fragment levels, EGFR, Met proto-oncogene, phospho-Met, and hepatocyte growth factor expression were not associated with the response to gefitinib treatment. Conclusion: These results suggest that, even if EGFR mutations were observed, a p-EGFR negative state might be a cause of intrinsic resistance to EGFR-TKIs.

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