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

Abstract

BackgroundThe 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.MethodsWe 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.ResultsThe 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).ConclusionsEGFR 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.Electronic supplementary materialThe online version of this article (10.1186/s12929-018-0451-3) contains supplementary material, which is available to authorized users.

Human Papillomavirus Oncoproteins Confer Sensitivity to Cisplatin by Interfering with Epidermal Growth Factor Receptor Nuclear Trafficking Related to More Favorable Clinical Survival Outcomes in Non-Small Cell Lung Cancer

“…The same study cohort described in our previous papers was enrolled with 243 paraffin-embedded lung cancer tissue blocks between 2008 and 2014 retrieved from Wan Fang Hospital, Taipei Medical University [ 5 , 11 ]. Clinical characteristics including age, gender, smoking history, histology, tumor stage, EGFR mutations, and the last follow-up date were obtained from patient medical records.…”

“…In addition to the classic EGFR signaling pathway, EGFR nuclear trafficking is involved in cancer progression through different cellular processes [ 9 , 10 ]. Our previous study reported that lung adenocarcinoma with different localizations of EGFR proteins responds favorably to platinum-based chemotherapy [ 11 ]. Therefore, the effect of EGFR nuclear trafficking on lung carcinogenesis should not be neglected.…”

Nuclear EGFR Expression Is Associated With Poor Survival in Laryngeal Carcinoma

“…T he membrane EGFR (mEGFR) protein overexpression is commonly found in many cancers. 1 Besides on the cell membrane, EGFR can be expressed in the cytoplasm (cytoplasmic EGFR) or translocated to the nucleus [nuclear EGFR (nEGFR)] through different mechanisms, which still need to be elucidated. 2,3 In the nucleus, EGFR acts as modulator of DNA replication, DNA repair, and gene transcription.…”

Racial disparities in histological subtype, stage, tumor grade and cancer-specific survival in lung cancer

“…Several studies had demonstrated that the mutation prevalence of epidermal growth factor receptor (EGFR) among Asian patients with lung adenocarcinoma was 50% to 60% compared with the 10% to 20% prevalence among White patients ( 41 , 42 ). And the EGFR mutation was associated with a better prognosis and better treatment response for patients with lung adenocarcinoma ( 43 ). Moreover, married status appeared to play an important role in lung cancer patients, especially in API patients.…”