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
N1 - Publisher Copyright:
© 2018 The Author(s).
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
KW - Prognosis
KW - Adenocarcinoma of Lung
KW - Humans
KW - Middle Aged
KW - Gene Expression Regulation, Neoplastic
KW - Male
KW - Cell Membrane/genetics
KW - Lung Neoplasms/genetics
KW - Disease-Free Survival
KW - ErbB Receptors/genetics
KW - Protein Kinase Inhibitors/administration & dosage
KW - Cell Nucleus/genetics
KW - Female
KW - Adenocarcinoma/genetics
KW - Aged
KW - Mutation
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U2 - 10.1186/s12929-018-0451-3
DO - 10.1186/s12929-018-0451-3
M3 - Article
C2 - 29950164
AN - SCOPUS:85049232842
SN - 1021-7770
VL - 25
JO - Journal of Biomedical Science
JF - Journal of Biomedical Science
IS - 1
M1 - 53
ER -