Association of the expression of mutant epidermal growth factor receptor protein as determined with mutation-specific antibodies in non-small cell lung cancer with progression-free survival after gefitinib treatment

Koichi Azuma, Isamu Okamoto, Akihiko Kawahara, Tomoki Taira, Kazutaka Nakashima, Satoshi Hattori, Takashi Kinoshita, Masayuki Takeda, Kazuhiko Nakagawa, Shinzo Takamori, Michihiko Kuwano, Mayumi Ono, Masayoshi Kage

Research output: Contribution to journalArticle

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Abstract

Introduction: Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with an increased response to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib in patients with non-small cell lung cancer (NSCLC). Although most NSCLC patients with EGFR mutations benefit from EGFR-TKI treatment, the efficacy of such treatment varies among individuals. Molecular markers for prediction of EGFR-TKI treatment efficacy in EGFR mutation-positive NSCLC have not been well defined. Methods: The expression of mutant EGFR proteins was quantitated by immunohistochemical analysis with mutation-specific antibodies in tumor specimens from 47 NSCLC patients with postoperative recurrent disease who harbored activating EGFR mutations. The expression score was determined from both the staining intensity and the proportion of tumor tissue expressing the mutant EGFR. Results: The median progression-free survival after the start of gefitinib treatment was significantly longer in patients with a high score for mutant EGFR expression than in those with a low score (12.2 versus 3.4 months, p < 0.001), whereas no significant difference in median overall survival was apparent between the two groups (24.9 versus 17.7 months, respectively, p = 0.144). This association between the expression score for mutant EGFR and progression-free survival was apparent both in patients with deletions in exon 19 of EGFR and in those with the L858R mutation in exon 21. Conclusions: Quantitative analysis of mutant EGFR expression by immunohistochemical analysis with mutation-specific antibodies may predict the efficacy of gefitinib treatment for EGFR mutation-positive NSCLC.

Original languageEnglish
Pages (from-to)122-127
Number of pages6
JournalJournal of Thoracic Oncology
Volume7
Issue number1
DOIs
Publication statusPublished - Jan 2012

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Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Disease-Free Survival
Mutation
Antibodies
Proteins
Therapeutics
Protein-Tyrosine Kinases
gefitinib
Exons
Neoplasm Antibodies
erbB-1 Genes
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine

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Association of the expression of mutant epidermal growth factor receptor protein as determined with mutation-specific antibodies in non-small cell lung cancer with progression-free survival after gefitinib treatment. / Azuma, Koichi; Okamoto, Isamu; Kawahara, Akihiko; Taira, Tomoki; Nakashima, Kazutaka; Hattori, Satoshi; Kinoshita, Takashi; Takeda, Masayuki; Nakagawa, Kazuhiko; Takamori, Shinzo; Kuwano, Michihiko; Ono, Mayumi; Kage, Masayoshi.

In: Journal of Thoracic Oncology, Vol. 7, No. 1, 01.2012, p. 122-127.

Research output: Contribution to journalArticle

Azuma, Koichi ; Okamoto, Isamu ; Kawahara, Akihiko ; Taira, Tomoki ; Nakashima, Kazutaka ; Hattori, Satoshi ; Kinoshita, Takashi ; Takeda, Masayuki ; Nakagawa, Kazuhiko ; Takamori, Shinzo ; Kuwano, Michihiko ; Ono, Mayumi ; Kage, Masayoshi. / Association of the expression of mutant epidermal growth factor receptor protein as determined with mutation-specific antibodies in non-small cell lung cancer with progression-free survival after gefitinib treatment. In: Journal of Thoracic Oncology. 2012 ; Vol. 7, No. 1. pp. 122-127.
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abstract = "Introduction: Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with an increased response to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib in patients with non-small cell lung cancer (NSCLC). Although most NSCLC patients with EGFR mutations benefit from EGFR-TKI treatment, the efficacy of such treatment varies among individuals. Molecular markers for prediction of EGFR-TKI treatment efficacy in EGFR mutation-positive NSCLC have not been well defined. Methods: The expression of mutant EGFR proteins was quantitated by immunohistochemical analysis with mutation-specific antibodies in tumor specimens from 47 NSCLC patients with postoperative recurrent disease who harbored activating EGFR mutations. The expression score was determined from both the staining intensity and the proportion of tumor tissue expressing the mutant EGFR. Results: The median progression-free survival after the start of gefitinib treatment was significantly longer in patients with a high score for mutant EGFR expression than in those with a low score (12.2 versus 3.4 months, p < 0.001), whereas no significant difference in median overall survival was apparent between the two groups (24.9 versus 17.7 months, respectively, p = 0.144). This association between the expression score for mutant EGFR and progression-free survival was apparent both in patients with deletions in exon 19 of EGFR and in those with the L858R mutation in exon 21. Conclusions: Quantitative analysis of mutant EGFR expression by immunohistochemical analysis with mutation-specific antibodies may predict the efficacy of gefitinib treatment for EGFR mutation-positive NSCLC.",
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AU - Azuma, Koichi

AU - Okamoto, Isamu

AU - Kawahara, Akihiko

AU - Taira, Tomoki

AU - Nakashima, Kazutaka

AU - Hattori, Satoshi

AU - Kinoshita, Takashi

AU - Takeda, Masayuki

AU - Nakagawa, Kazuhiko

AU - Takamori, Shinzo

AU - Kuwano, Michihiko

AU - Ono, Mayumi

AU - Kage, Masayoshi

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N2 - Introduction: Somatic mutations in the epidermal growth factor receptor (EGFR) gene are associated with an increased response to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib in patients with non-small cell lung cancer (NSCLC). Although most NSCLC patients with EGFR mutations benefit from EGFR-TKI treatment, the efficacy of such treatment varies among individuals. Molecular markers for prediction of EGFR-TKI treatment efficacy in EGFR mutation-positive NSCLC have not been well defined. Methods: The expression of mutant EGFR proteins was quantitated by immunohistochemical analysis with mutation-specific antibodies in tumor specimens from 47 NSCLC patients with postoperative recurrent disease who harbored activating EGFR mutations. The expression score was determined from both the staining intensity and the proportion of tumor tissue expressing the mutant EGFR. Results: The median progression-free survival after the start of gefitinib treatment was significantly longer in patients with a high score for mutant EGFR expression than in those with a low score (12.2 versus 3.4 months, p < 0.001), whereas no significant difference in median overall survival was apparent between the two groups (24.9 versus 17.7 months, respectively, p = 0.144). This association between the expression score for mutant EGFR and progression-free survival was apparent both in patients with deletions in exon 19 of EGFR and in those with the L858R mutation in exon 21. Conclusions: Quantitative analysis of mutant EGFR expression by immunohistochemical analysis with mutation-specific antibodies may predict the efficacy of gefitinib treatment for EGFR mutation-positive NSCLC.

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