Comprehensive analysis of EGFR signaling pathways in Japanese patients with non-small cell lung cancer

Shinobu Hosokawa, Shinichi Toyooka, Yoshiro Fujiwara, Masaki Tokumo, Junichi Sou, Nagio Takigawa, Katsuyuki Hotta, Tadashi Yoshino, Hiroshi Date, Mitsune Tanimoto, Katsuyuki Kiura

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Purpose: Translational approach is essentially needed to return the achievement of basic researches to oncological practice. The molecular associations among EGFR mutation and the components of EGFR signaling pathways have been extensively studied in laboratory experiments, although were still controversial. Moreover, the impact of downstream signaling of EGFR on clinical features in patients with non-small cell lung cancer (NSCLC) remains undetermined. Patients and methods: A total of 93 surgically resected NSCLC patients were recruited the study. EGFR mutation status was analyzed by direct sequence method. The protein expression levels of EGFR, phosphorylated EGFR (pEGFR), phosphorylated Akt (pAkt), and phosphorylated MAPK (pMAPK) were determined by immunohistochemistry. Results: There were 37 (40%) patients whose tumor harboring EGFR mutations (1 in exon 18, 22 in exon 19, and 14 in exon 21). Protein expression of EGFR, pEGFR, pAkt, and pMAPK was detected in 61 (66%), 27 (29%), 58 (62%), and 41 (44%) patients, respectively. The expression of pAkt was significantly associated with female gender and never-smoking history, and it was frequently upregulated in tumors harboring EGFR mutations (p <0.05, each). Phosphorylation of EGFR was closely correlated with the EGFR protein expression (p <0.05), but not with the EGFR mutations. In regard to patient survival, none of the molecular biomarkers was predictive for survival after surgical resection, but pMAPK expression was predictive for poor prognosis after gefitinib treatment in patients with postoperative recurrence (p <0.05), suggesting the strong linkage between pMAPK expression and survival benefit from gefitinib. Conclusion: Our result could provide new insight into MAP kinase signaling when we treat NSCLC patients with gefitinib.

Original languageEnglish
Pages (from-to)107-113
Number of pages7
JournalLung Cancer
Volume66
Issue number1
DOIs
Publication statusPublished - Oct 2009

Fingerprint

Non-Small Cell Lung Carcinoma
Mutation
Exons
Survival
Proteins
Neoplasms
Phosphotransferases
Biomarkers
Smoking
History
Immunohistochemistry
Phosphorylation
Recurrence
Research
gefitinib

Keywords

  • EGFR mutation
  • EGFR protein
  • Gefitinib
  • Immunohistochemistry
  • Non-small cell lung cancer
  • pAkt
  • pEGFR
  • pMAPK
  • Prognostic factor

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Comprehensive analysis of EGFR signaling pathways in Japanese patients with non-small cell lung cancer. / Hosokawa, Shinobu; Toyooka, Shinichi; Fujiwara, Yoshiro; Tokumo, Masaki; Sou, Junichi; Takigawa, Nagio; Hotta, Katsuyuki; Yoshino, Tadashi; Date, Hiroshi; Tanimoto, Mitsune; Kiura, Katsuyuki.

In: Lung Cancer, Vol. 66, No. 1, 10.2009, p. 107-113.

Research output: Contribution to journalArticle

Hosokawa, Shinobu ; Toyooka, Shinichi ; Fujiwara, Yoshiro ; Tokumo, Masaki ; Sou, Junichi ; Takigawa, Nagio ; Hotta, Katsuyuki ; Yoshino, Tadashi ; Date, Hiroshi ; Tanimoto, Mitsune ; Kiura, Katsuyuki. / Comprehensive analysis of EGFR signaling pathways in Japanese patients with non-small cell lung cancer. In: Lung Cancer. 2009 ; Vol. 66, No. 1. pp. 107-113.
@article{7e382bee234448f49496df7cf0dca330,
title = "Comprehensive analysis of EGFR signaling pathways in Japanese patients with non-small cell lung cancer",
abstract = "Purpose: Translational approach is essentially needed to return the achievement of basic researches to oncological practice. The molecular associations among EGFR mutation and the components of EGFR signaling pathways have been extensively studied in laboratory experiments, although were still controversial. Moreover, the impact of downstream signaling of EGFR on clinical features in patients with non-small cell lung cancer (NSCLC) remains undetermined. Patients and methods: A total of 93 surgically resected NSCLC patients were recruited the study. EGFR mutation status was analyzed by direct sequence method. The protein expression levels of EGFR, phosphorylated EGFR (pEGFR), phosphorylated Akt (pAkt), and phosphorylated MAPK (pMAPK) were determined by immunohistochemistry. Results: There were 37 (40{\%}) patients whose tumor harboring EGFR mutations (1 in exon 18, 22 in exon 19, and 14 in exon 21). Protein expression of EGFR, pEGFR, pAkt, and pMAPK was detected in 61 (66{\%}), 27 (29{\%}), 58 (62{\%}), and 41 (44{\%}) patients, respectively. The expression of pAkt was significantly associated with female gender and never-smoking history, and it was frequently upregulated in tumors harboring EGFR mutations (p <0.05, each). Phosphorylation of EGFR was closely correlated with the EGFR protein expression (p <0.05), but not with the EGFR mutations. In regard to patient survival, none of the molecular biomarkers was predictive for survival after surgical resection, but pMAPK expression was predictive for poor prognosis after gefitinib treatment in patients with postoperative recurrence (p <0.05), suggesting the strong linkage between pMAPK expression and survival benefit from gefitinib. Conclusion: Our result could provide new insight into MAP kinase signaling when we treat NSCLC patients with gefitinib.",
keywords = "EGFR mutation, EGFR protein, Gefitinib, Immunohistochemistry, Non-small cell lung cancer, pAkt, pEGFR, pMAPK, Prognostic factor",
author = "Shinobu Hosokawa and Shinichi Toyooka and Yoshiro Fujiwara and Masaki Tokumo and Junichi Sou and Nagio Takigawa and Katsuyuki Hotta and Tadashi Yoshino and Hiroshi Date and Mitsune Tanimoto and Katsuyuki Kiura",
year = "2009",
month = "10",
doi = "10.1016/j.lungcan.2009.01.005",
language = "English",
volume = "66",
pages = "107--113",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Comprehensive analysis of EGFR signaling pathways in Japanese patients with non-small cell lung cancer

AU - Hosokawa, Shinobu

AU - Toyooka, Shinichi

AU - Fujiwara, Yoshiro

AU - Tokumo, Masaki

AU - Sou, Junichi

AU - Takigawa, Nagio

AU - Hotta, Katsuyuki

AU - Yoshino, Tadashi

AU - Date, Hiroshi

AU - Tanimoto, Mitsune

AU - Kiura, Katsuyuki

PY - 2009/10

Y1 - 2009/10

N2 - Purpose: Translational approach is essentially needed to return the achievement of basic researches to oncological practice. The molecular associations among EGFR mutation and the components of EGFR signaling pathways have been extensively studied in laboratory experiments, although were still controversial. Moreover, the impact of downstream signaling of EGFR on clinical features in patients with non-small cell lung cancer (NSCLC) remains undetermined. Patients and methods: A total of 93 surgically resected NSCLC patients were recruited the study. EGFR mutation status was analyzed by direct sequence method. The protein expression levels of EGFR, phosphorylated EGFR (pEGFR), phosphorylated Akt (pAkt), and phosphorylated MAPK (pMAPK) were determined by immunohistochemistry. Results: There were 37 (40%) patients whose tumor harboring EGFR mutations (1 in exon 18, 22 in exon 19, and 14 in exon 21). Protein expression of EGFR, pEGFR, pAkt, and pMAPK was detected in 61 (66%), 27 (29%), 58 (62%), and 41 (44%) patients, respectively. The expression of pAkt was significantly associated with female gender and never-smoking history, and it was frequently upregulated in tumors harboring EGFR mutations (p <0.05, each). Phosphorylation of EGFR was closely correlated with the EGFR protein expression (p <0.05), but not with the EGFR mutations. In regard to patient survival, none of the molecular biomarkers was predictive for survival after surgical resection, but pMAPK expression was predictive for poor prognosis after gefitinib treatment in patients with postoperative recurrence (p <0.05), suggesting the strong linkage between pMAPK expression and survival benefit from gefitinib. Conclusion: Our result could provide new insight into MAP kinase signaling when we treat NSCLC patients with gefitinib.

AB - Purpose: Translational approach is essentially needed to return the achievement of basic researches to oncological practice. The molecular associations among EGFR mutation and the components of EGFR signaling pathways have been extensively studied in laboratory experiments, although were still controversial. Moreover, the impact of downstream signaling of EGFR on clinical features in patients with non-small cell lung cancer (NSCLC) remains undetermined. Patients and methods: A total of 93 surgically resected NSCLC patients were recruited the study. EGFR mutation status was analyzed by direct sequence method. The protein expression levels of EGFR, phosphorylated EGFR (pEGFR), phosphorylated Akt (pAkt), and phosphorylated MAPK (pMAPK) were determined by immunohistochemistry. Results: There were 37 (40%) patients whose tumor harboring EGFR mutations (1 in exon 18, 22 in exon 19, and 14 in exon 21). Protein expression of EGFR, pEGFR, pAkt, and pMAPK was detected in 61 (66%), 27 (29%), 58 (62%), and 41 (44%) patients, respectively. The expression of pAkt was significantly associated with female gender and never-smoking history, and it was frequently upregulated in tumors harboring EGFR mutations (p <0.05, each). Phosphorylation of EGFR was closely correlated with the EGFR protein expression (p <0.05), but not with the EGFR mutations. In regard to patient survival, none of the molecular biomarkers was predictive for survival after surgical resection, but pMAPK expression was predictive for poor prognosis after gefitinib treatment in patients with postoperative recurrence (p <0.05), suggesting the strong linkage between pMAPK expression and survival benefit from gefitinib. Conclusion: Our result could provide new insight into MAP kinase signaling when we treat NSCLC patients with gefitinib.

KW - EGFR mutation

KW - EGFR protein

KW - Gefitinib

KW - Immunohistochemistry

KW - Non-small cell lung cancer

KW - pAkt

KW - pEGFR

KW - pMAPK

KW - Prognostic factor

UR - http://www.scopus.com/inward/record.url?scp=68949219078&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68949219078&partnerID=8YFLogxK

U2 - 10.1016/j.lungcan.2009.01.005

DO - 10.1016/j.lungcan.2009.01.005

M3 - Article

C2 - 19185949

AN - SCOPUS:68949219078

VL - 66

SP - 107

EP - 113

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

IS - 1

ER -