Clinicopathologic significance of the mutations of the epidermal growth factor receptor gene in patients with non-small cell lung cancer

Yoshio Tomizawa, Hironobu Iijima, Noriaki Sunaga, Koji Sato, Atsushi Takise, Yoshimi Otani, Shigefumi Tanaka, Tatsuo Suga, Ryusei Saito, Tamotsu Ishizuka, Kunio Dobashi, John D. Minna, Takashi Nakajima, Masatomo Mori

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Abstract

Purpose: It has been reported that the mutations of epidermal growth factor receptor (EGFR) are detected in lung cancers. Studies of EGFR mutations in large numbers of patients' tumors with clinical data including response to EGFR tyrosine kinase directed therapy are needed to develop a robust database for clinical use. The purpose of the present study is to gain further insights into the significance of EGFR mutation in non-small cell lung cancer (NSCLC). Experimental Design: We investigated the clinicopathologic significance of tyrosine kinase domain (exons 18-21) EGFR mutations in 120 patients with primary NSCLC and the correlation between EGFR mutation and sensitivity to gefitinib in an additional 20 NSCLC patients treated with gefitinib. In addition, onocogenic KRAS mutations and RASSF1A promoter methylation were determined in the same samples. Results: EGFR mutation was detected in 29 of 120 (24%) tumors. All of the 29 (40%) mutations occurred in 72 adenocarcinomas. EGFR mutation was significantly more frequent in females (47%) than males (12%, P < 0.0001), in younger patients (38%) than older patients (10%, P = 0.0005), in nonsmokers (47%) than smokers (13%, P < 0.0001), and in well-differentiated tumors (39%) than moderately and poorly differentiated tumors (7%, P < 0.0001). Mutation of the EGFR gene was preferentially observed in advanced disease. Furthermore, EGFR mutations were detected in 11 of 14 (79%) responders, whereas none of six (0%) nonresponders had the mutation (P = 0.0022). Conclusions: These results in Japanese (East Asian) patients indicated that EGFR mutation plays an important role in pathogenesis of lung adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)6816-6822
Number of pages7
JournalClinical Cancer Research
Volume11
Issue number19 I
DOIs
StatePublished - Oct 1 2005

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erbB-1 Genes
Non-Small Cell Lung Carcinoma
Epidermal Growth Factor Receptor
Mutation
Protein-Tyrosine Kinases
Neoplasms
Methylation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Clinicopathologic significance of the mutations of the epidermal growth factor receptor gene in patients with non-small cell lung cancer. / Tomizawa, Yoshio; Iijima, Hironobu; Sunaga, Noriaki; Sato, Koji; Takise, Atsushi; Otani, Yoshimi; Tanaka, Shigefumi; Suga, Tatsuo; Saito, Ryusei; Ishizuka, Tamotsu; Dobashi, Kunio; Minna, John D.; Nakajima, Takashi; Mori, Masatomo.

In: Clinical Cancer Research, Vol. 11, No. 19 I, 01.10.2005, p. 6816-6822.

Research output: Contribution to journalArticle

Tomizawa, Y, Iijima, H, Sunaga, N, Sato, K, Takise, A, Otani, Y, Tanaka, S, Suga, T, Saito, R, Ishizuka, T, Dobashi, K, Minna, JD, Nakajima, T & Mori, M 2005, 'Clinicopathologic significance of the mutations of the epidermal growth factor receptor gene in patients with non-small cell lung cancer', Clinical Cancer Research, vol. 11, no. 19 I, pp. 6816-6822. https://doi.org/10.1158/1078-0432.CCR-05-0441
Tomizawa, Yoshio ; Iijima, Hironobu ; Sunaga, Noriaki ; Sato, Koji ; Takise, Atsushi ; Otani, Yoshimi ; Tanaka, Shigefumi ; Suga, Tatsuo ; Saito, Ryusei ; Ishizuka, Tamotsu ; Dobashi, Kunio ; Minna, John D. ; Nakajima, Takashi ; Mori, Masatomo. / Clinicopathologic significance of the mutations of the epidermal growth factor receptor gene in patients with non-small cell lung cancer. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 19 I. pp. 6816-6822.
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abstract = "Purpose: It has been reported that the mutations of epidermal growth factor receptor (EGFR) are detected in lung cancers. Studies of EGFR mutations in large numbers of patients' tumors with clinical data including response to EGFR tyrosine kinase directed therapy are needed to develop a robust database for clinical use. The purpose of the present study is to gain further insights into the significance of EGFR mutation in non-small cell lung cancer (NSCLC). Experimental Design: We investigated the clinicopathologic significance of tyrosine kinase domain (exons 18-21) EGFR mutations in 120 patients with primary NSCLC and the correlation between EGFR mutation and sensitivity to gefitinib in an additional 20 NSCLC patients treated with gefitinib. In addition, onocogenic KRAS mutations and RASSF1A promoter methylation were determined in the same samples. Results: EGFR mutation was detected in 29 of 120 (24{\%}) tumors. All of the 29 (40{\%}) mutations occurred in 72 adenocarcinomas. EGFR mutation was significantly more frequent in females (47{\%}) than males (12{\%}, P < 0.0001), in younger patients (38{\%}) than older patients (10{\%}, P = 0.0005), in nonsmokers (47{\%}) than smokers (13{\%}, P < 0.0001), and in well-differentiated tumors (39{\%}) than moderately and poorly differentiated tumors (7{\%}, P < 0.0001). Mutation of the EGFR gene was preferentially observed in advanced disease. Furthermore, EGFR mutations were detected in 11 of 14 (79{\%}) responders, whereas none of six (0{\%}) nonresponders had the mutation (P = 0.0022). Conclusions: These results in Japanese (East Asian) patients indicated that EGFR mutation plays an important role in pathogenesis of lung adenocarcinoma.",
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T1 - Clinicopathologic significance of the mutations of the epidermal growth factor receptor gene in patients with non-small cell lung cancer

AU - Tomizawa, Yoshio

AU - Iijima, Hironobu

AU - Sunaga, Noriaki

AU - Sato, Koji

AU - Takise, Atsushi

AU - Otani, Yoshimi

AU - Tanaka, Shigefumi

AU - Suga, Tatsuo

AU - Saito, Ryusei

AU - Ishizuka, Tamotsu

AU - Dobashi, Kunio

AU - Minna, John D.

AU - Nakajima, Takashi

AU - Mori, Masatomo

PY - 2005/10/1

Y1 - 2005/10/1

N2 - Purpose: It has been reported that the mutations of epidermal growth factor receptor (EGFR) are detected in lung cancers. Studies of EGFR mutations in large numbers of patients' tumors with clinical data including response to EGFR tyrosine kinase directed therapy are needed to develop a robust database for clinical use. The purpose of the present study is to gain further insights into the significance of EGFR mutation in non-small cell lung cancer (NSCLC). Experimental Design: We investigated the clinicopathologic significance of tyrosine kinase domain (exons 18-21) EGFR mutations in 120 patients with primary NSCLC and the correlation between EGFR mutation and sensitivity to gefitinib in an additional 20 NSCLC patients treated with gefitinib. In addition, onocogenic KRAS mutations and RASSF1A promoter methylation were determined in the same samples. Results: EGFR mutation was detected in 29 of 120 (24%) tumors. All of the 29 (40%) mutations occurred in 72 adenocarcinomas. EGFR mutation was significantly more frequent in females (47%) than males (12%, P < 0.0001), in younger patients (38%) than older patients (10%, P = 0.0005), in nonsmokers (47%) than smokers (13%, P < 0.0001), and in well-differentiated tumors (39%) than moderately and poorly differentiated tumors (7%, P < 0.0001). Mutation of the EGFR gene was preferentially observed in advanced disease. Furthermore, EGFR mutations were detected in 11 of 14 (79%) responders, whereas none of six (0%) nonresponders had the mutation (P = 0.0022). Conclusions: These results in Japanese (East Asian) patients indicated that EGFR mutation plays an important role in pathogenesis of lung adenocarcinoma.

AB - Purpose: It has been reported that the mutations of epidermal growth factor receptor (EGFR) are detected in lung cancers. Studies of EGFR mutations in large numbers of patients' tumors with clinical data including response to EGFR tyrosine kinase directed therapy are needed to develop a robust database for clinical use. The purpose of the present study is to gain further insights into the significance of EGFR mutation in non-small cell lung cancer (NSCLC). Experimental Design: We investigated the clinicopathologic significance of tyrosine kinase domain (exons 18-21) EGFR mutations in 120 patients with primary NSCLC and the correlation between EGFR mutation and sensitivity to gefitinib in an additional 20 NSCLC patients treated with gefitinib. In addition, onocogenic KRAS mutations and RASSF1A promoter methylation were determined in the same samples. Results: EGFR mutation was detected in 29 of 120 (24%) tumors. All of the 29 (40%) mutations occurred in 72 adenocarcinomas. EGFR mutation was significantly more frequent in females (47%) than males (12%, P < 0.0001), in younger patients (38%) than older patients (10%, P = 0.0005), in nonsmokers (47%) than smokers (13%, P < 0.0001), and in well-differentiated tumors (39%) than moderately and poorly differentiated tumors (7%, P < 0.0001). Mutation of the EGFR gene was preferentially observed in advanced disease. Furthermore, EGFR mutations were detected in 11 of 14 (79%) responders, whereas none of six (0%) nonresponders had the mutation (P = 0.0022). Conclusions: These results in Japanese (East Asian) patients indicated that EGFR mutation plays an important role in pathogenesis of lung adenocarcinoma.

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