具有细支气管肺泡成分的腺癌中的表皮生长因子受体信号传导

Epidermal growth factor receptor signaling in adenocarcinomas with bronchioloalveolar components.

作者信息

Sarkaria Inderpal S, Zakowski Maureen F, Pham Duykhanh, Hezel Michael, Ebright Michael I, Chuai Shaokun, Venkatraman Ennapadam S, Kris Mark G, Rusch Valerie W, Singh Bhuvanesh

机构信息

Laboratory of Epithelial Cancer Biology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

出版信息

Ann Thorac Surg. 2008 Jan;85(1):216-23. doi: 10.1016/j.athoracsur.2007.07.046.

DOI:10.1016/j.athoracsur.2007.07.046

PMID:18154814

Abstract

BACKGROUND

Epidermal growth factor receptor (EGFR) has gained importance in non-small cell lung cancer given impressive responses to agents targeting this molecule, particularly in bronchioloalveolar carcinoma (BAC) and adenocarcinomas, mixed subtype, with BAC components (adeno/BAC). This study assesses EGFR signaling in these tumors.

METHODS

One hundred fifty tumors were classified as BAC or adeno/BAC. Tumor marker expression was determined by immunohistochemistry. Correlations with expression were examined for all tumors (BAC and adeno/BAC), and by BAC and adeno/BAC subset analyses.

RESULTS

Positive immunophenotype was observed in 40.6% of tumors for EGFR, 51.3% for p-AKT, 58.7% for p-ERK, and 28.0% for PTEN, with increased overexpression of EGFR (p = 0.025) and p-AKT (p < 0.0001) in adeno/BAC. Epidermal growth factor receptor immunophenotype was greater in never-smokers (p = 0.008) and correlated with improved overall survival (p = 0.018). On subset analysis, EGFR correlated with improved overall survival (p = 0.05) and disease-free interval (p = 0.044) only in adeno/BAC. Epidermal growth factor receptor independently predicted improved disease-free interval in adeno/BAC (p = 0.03; hazard ratio, 0.47; 95% confidence interval, 0.23 to 0.94).

CONCLUSIONS

Overexpression of EGFR in lung adenocarcinomas with components of BAC histology correlate with never-smoker status and improved overall survival and disease-free interval. Epidermal growth factor receptor immunophenotype may be a useful predictor of clinical outcomes in this tumor subset.

摘要

背景

鉴于针对表皮生长因子受体（EGFR）的药物取得了显著疗效，尤其是在细支气管肺泡癌（BAC）以及具有BAC成分的混合型腺癌（腺/ BAC）中，EGFR在非小细胞肺癌中的重要性日益凸显。本研究评估了这些肿瘤中的EGFR信号传导。

方法

150例肿瘤被分类为BAC或腺/ BAC。通过免疫组织化学确定肿瘤标志物表达。对所有肿瘤（BAC和腺/ BAC）以及通过BAC和腺/ BAC亚组分析来检查与表达的相关性。

结果

EGFR的阳性免疫表型在40.6%的肿瘤中观察到，p-AKT为51.3%，p-ERK为58.7%，PTEN为28.0%，腺/ BAC中EGFR（p = 0.025）和p-AKT（p < 0.0001）的过表达增加。表皮生长因子受体免疫表型在从不吸烟者中更高（p = 0.008），并与总体生存率提高相关（p = 0.018）。在亚组分析中，EGFR仅在腺/ BAC中与总体生存率提高（p = 0.05）和无病间期（p = 0.044）相关。表皮生长因子受体独立预测腺/ BAC中无病间期改善（p = 0.03；风险比，0.47；95%置信区间，0.23至0.94）。