Abstract

Background: The nuclear translocation of epidermal growth factor receptor (EGFR) has been considered to play a role in carcinogenesis. However, the relevance of differentially located EGFR proteins in lung cancer remains unclear. Methods: We examined 161 patients with primary lung adenocarcinoma to detect EGFR expression in lung cancer cells using immunohistochemistry and determined the correlations of EGFR expression with clinical characteristics, EGFR mutations, and survival time. Moreover, we graded complete membranous staining with strong intensity as high membranous EGFR (mEGFR) expression, and nuclear EGFR staining with strong intensity as high nuclear (nEGFR) expression. Results: The prevalence of high mEGFR and nEGFR expression in lung adenocarcinoma was 42.86 and 39.13%, respectively. After multivariate analyses, high mEGFR expression was associated with a significantly reduced mortality risk in older patients, those with a history of smoking, and those without brain metastasis (hazard ratio[95% confidential interval], HR[95% CI] = 0.55[0.32~ 0.92]; 0.51[0.26~ 0.98] and 0.56[0.33~ 0.94], in overall survival, respectively). An association between high nEGFR expression and early recurrence was observed in patients with metastasis (HR[95% CI] =1.68[1.05~ 2.68], in progression-free survival). Notably, patients with low mEGFR and low nEGFR expression had the lowest survival rate in cases without brain metastasis (p = 0.018) and with a history of smoking (p = 0.062) and total EGFR (any high mEGFR or nEGFR) expression indicated a more favorable response to platinum-based chemotherapy regardless of EGFR mutations (HR[95% CI] =0.33[0.12-0.92]; adjusted HR[95% CI] = 0.36[0.13~ 1.02] with the use of tyrosine kinase inhibitor). Conclusions: EGFR proteins at different cellular locations in lung adenocarcinoma might influence the biology of cancer cells and are an independent indicator of more favorable prognosis and treatment response.

Original languageEnglish
Article number53
JournalJournal of Biomedical Science
Volume25
Issue number1
DOIs
Publication statusPublished - Jun 28 2018

Fingerprint

Epidermal Growth Factor Receptor
Neoplasm Metastasis
Lung Neoplasms
Brain
Smoking
Cells
Adenocarcinoma of lung
Staining and Labeling
Mutation
Chemotherapy
Survival
Platinum
Protein-Tyrosine Kinases
Disease-Free Survival
Cell Biology
Hazards
Carcinogenesis
Proteins
Multivariate Analysis
Survival Rate

Keywords

  • Epidermal growth factor receptor
  • Immunohistochemistry
  • Localization
  • Lung adenocarcinoma
  • Survival

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Pharmacology (medical)

Cite this

@article{5544f55763874f87aeceafc5aa7411e9,
title = "Prognostic value of localization of epidermal growth factor receptor in lung adenocarcinoma",
abstract = "Background: The nuclear translocation of epidermal growth factor receptor (EGFR) has been considered to play a role in carcinogenesis. However, the relevance of differentially located EGFR proteins in lung cancer remains unclear. Methods: We examined 161 patients with primary lung adenocarcinoma to detect EGFR expression in lung cancer cells using immunohistochemistry and determined the correlations of EGFR expression with clinical characteristics, EGFR mutations, and survival time. Moreover, we graded complete membranous staining with strong intensity as high membranous EGFR (mEGFR) expression, and nuclear EGFR staining with strong intensity as high nuclear (nEGFR) expression. Results: The prevalence of high mEGFR and nEGFR expression in lung adenocarcinoma was 42.86 and 39.13{\%}, respectively. After multivariate analyses, high mEGFR expression was associated with a significantly reduced mortality risk in older patients, those with a history of smoking, and those without brain metastasis (hazard ratio[95{\%} confidential interval], HR[95{\%} CI] = 0.55[0.32~ 0.92]; 0.51[0.26~ 0.98] and 0.56[0.33~ 0.94], in overall survival, respectively). An association between high nEGFR expression and early recurrence was observed in patients with metastasis (HR[95{\%} CI] =1.68[1.05~ 2.68], in progression-free survival). Notably, patients with low mEGFR and low nEGFR expression had the lowest survival rate in cases without brain metastasis (p = 0.018) and with a history of smoking (p = 0.062) and total EGFR (any high mEGFR or nEGFR) expression indicated a more favorable response to platinum-based chemotherapy regardless of EGFR mutations (HR[95{\%} CI] =0.33[0.12-0.92]; adjusted HR[95{\%} CI] = 0.36[0.13~ 1.02] with the use of tyrosine kinase inhibitor). Conclusions: EGFR proteins at different cellular locations in lung adenocarcinoma might influence the biology of cancer cells and are an independent indicator of more favorable prognosis and treatment response.",
keywords = "Epidermal growth factor receptor, Immunohistochemistry, Localization, Lung adenocarcinoma, Survival",
author = "Wang, {Jinn Li} and Fang, {Chia Lang} and Tzeng, {Yu Tien} and Hsu, {Han Lin} and Lin, {Sey En} and Yu, {Ming Chih} and Bai, {Kuan Jen} and Wang, {Liang Shun} and Liu, {Hsingjin Eugene}",
year = "2018",
month = "6",
day = "28",
doi = "10.1186/s12929-018-0451-3",
language = "English",
volume = "25",
journal = "Journal of Biomedical Science",
issn = "1021-7770",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Prognostic value of localization of epidermal growth factor receptor in lung adenocarcinoma

AU - Wang, Jinn Li

AU - Fang, Chia Lang

AU - Tzeng, Yu Tien

AU - Hsu, Han Lin

AU - Lin, Sey En

AU - Yu, Ming Chih

AU - Bai, Kuan Jen

AU - Wang, Liang Shun

AU - Liu, Hsingjin Eugene

PY - 2018/6/28

Y1 - 2018/6/28

N2 - Background: The nuclear translocation of epidermal growth factor receptor (EGFR) has been considered to play a role in carcinogenesis. However, the relevance of differentially located EGFR proteins in lung cancer remains unclear. Methods: We examined 161 patients with primary lung adenocarcinoma to detect EGFR expression in lung cancer cells using immunohistochemistry and determined the correlations of EGFR expression with clinical characteristics, EGFR mutations, and survival time. Moreover, we graded complete membranous staining with strong intensity as high membranous EGFR (mEGFR) expression, and nuclear EGFR staining with strong intensity as high nuclear (nEGFR) expression. Results: The prevalence of high mEGFR and nEGFR expression in lung adenocarcinoma was 42.86 and 39.13%, respectively. After multivariate analyses, high mEGFR expression was associated with a significantly reduced mortality risk in older patients, those with a history of smoking, and those without brain metastasis (hazard ratio[95% confidential interval], HR[95% CI] = 0.55[0.32~ 0.92]; 0.51[0.26~ 0.98] and 0.56[0.33~ 0.94], in overall survival, respectively). An association between high nEGFR expression and early recurrence was observed in patients with metastasis (HR[95% CI] =1.68[1.05~ 2.68], in progression-free survival). Notably, patients with low mEGFR and low nEGFR expression had the lowest survival rate in cases without brain metastasis (p = 0.018) and with a history of smoking (p = 0.062) and total EGFR (any high mEGFR or nEGFR) expression indicated a more favorable response to platinum-based chemotherapy regardless of EGFR mutations (HR[95% CI] =0.33[0.12-0.92]; adjusted HR[95% CI] = 0.36[0.13~ 1.02] with the use of tyrosine kinase inhibitor). Conclusions: EGFR proteins at different cellular locations in lung adenocarcinoma might influence the biology of cancer cells and are an independent indicator of more favorable prognosis and treatment response.

AB - Background: The nuclear translocation of epidermal growth factor receptor (EGFR) has been considered to play a role in carcinogenesis. However, the relevance of differentially located EGFR proteins in lung cancer remains unclear. Methods: We examined 161 patients with primary lung adenocarcinoma to detect EGFR expression in lung cancer cells using immunohistochemistry and determined the correlations of EGFR expression with clinical characteristics, EGFR mutations, and survival time. Moreover, we graded complete membranous staining with strong intensity as high membranous EGFR (mEGFR) expression, and nuclear EGFR staining with strong intensity as high nuclear (nEGFR) expression. Results: The prevalence of high mEGFR and nEGFR expression in lung adenocarcinoma was 42.86 and 39.13%, respectively. After multivariate analyses, high mEGFR expression was associated with a significantly reduced mortality risk in older patients, those with a history of smoking, and those without brain metastasis (hazard ratio[95% confidential interval], HR[95% CI] = 0.55[0.32~ 0.92]; 0.51[0.26~ 0.98] and 0.56[0.33~ 0.94], in overall survival, respectively). An association between high nEGFR expression and early recurrence was observed in patients with metastasis (HR[95% CI] =1.68[1.05~ 2.68], in progression-free survival). Notably, patients with low mEGFR and low nEGFR expression had the lowest survival rate in cases without brain metastasis (p = 0.018) and with a history of smoking (p = 0.062) and total EGFR (any high mEGFR or nEGFR) expression indicated a more favorable response to platinum-based chemotherapy regardless of EGFR mutations (HR[95% CI] =0.33[0.12-0.92]; adjusted HR[95% CI] = 0.36[0.13~ 1.02] with the use of tyrosine kinase inhibitor). Conclusions: EGFR proteins at different cellular locations in lung adenocarcinoma might influence the biology of cancer cells and are an independent indicator of more favorable prognosis and treatment response.

KW - Epidermal growth factor receptor

KW - Immunohistochemistry

KW - Localization

KW - Lung adenocarcinoma

KW - Survival

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U2 - 10.1186/s12929-018-0451-3

DO - 10.1186/s12929-018-0451-3

M3 - Article

VL - 25

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

SN - 1021-7770

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M1 - 53

ER -