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
Issue number1
Publication statusPublished - Jun 28 2018


  • Epidermal growth factor receptor
  • Immunohistochemistry
  • Localization
  • Lung adenocarcinoma
  • Survival
  • Prognosis
  • Adenocarcinoma of Lung
  • Humans
  • Middle Aged
  • Gene Expression Regulation, Neoplastic
  • Male
  • Cell Membrane/genetics
  • Lung Neoplasms/genetics
  • Disease-Free Survival
  • ErbB Receptors/genetics
  • Protein Kinase Inhibitors/administration & dosage
  • Cell Nucleus/genetics
  • Female
  • Adenocarcinoma/genetics
  • Aged
  • Mutation

ASJC Scopus subject areas

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


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