肺腺癌中表皮生长因子受体定位的预后价值。
Prognostic value of localization of epidermal growth factor receptor in lung adenocarcinoma.
机构信息
Division of Hematology Oncology, Department of Pediatrics, Wan Fang Hospital, Taipei Medical University, No.111, Sec. 3, Xinglong Rd, Wenshan Dist, 11696, Taipei, Taiwan.
Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, 250 Wuxing St. Taipei, 11031, Taipei, Taiwan.
出版信息
J Biomed Sci. 2018 Jun 28;25(1):53. doi: 10.1186/s12929-018-0451-3.
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.
背景
表皮生长因子受体（EGFR）的核转位被认为在致癌作用中发挥作用。然而，肺癌中不同位置的 EGFR 蛋白的相关性尚不清楚。
方法
我们检测了 161 例原发性肺腺癌患者，使用免疫组织化学检测肺癌细胞中的 EGFR 表达，并确定 EGFR 表达与临床特征、EGFR 突变和生存时间的相关性。此外，我们将完整的膜染色强度评为高膜 EGFR（mEGFR）表达，将核 EGFR 染色强度评为高强度核（nEGFR）表达。
结果
肺腺癌中高 mEGFR 和 nEGFR 表达的发生率分别为 42.86%和 39.13%。多变量分析后，高 mEGFR 表达与老年患者、有吸烟史和无脑转移患者的死亡率降低显著相关（风险比[95%置信区间]，HR[95%CI]分别为 0.55[0.320.92]、0.51[0.260.98]和 0.56[0.330.94]；总生存率）。在有转移的患者中观察到高 nEGFR 表达与早期复发有关（无进展生存率，HR[95%CI] =1.68[1.052.68]）。值得注意的是，无脑转移患者（p=0.018）和有吸烟史患者（p=0.062）中低 mEGFR 和低 nEGFR 表达的患者生存率最低，无论 EGFR 突变与否，总 EGFR（任何高 mEGFR 或 nEGFR）表达均表明对铂类化疗的反应更有利（风险比[95%CI] =0.33[0.120.92]；调整风险比[95%CI] =0.36[0.131.02]使用酪氨酸激酶抑制剂）。
结论
肺腺癌中不同细胞位置的 EGFR 蛋白可能影响癌细胞的生物学特性，是预后和治疗反应更有利的独立指标。
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