Activation state egfr and STAT-3 as prognostic markers in resected non-small cell lung cancer
Activation state egfr and STAT-3 as prognostic markers in resected non-small cell lung cancer
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DOI：
10.1016/j.lungcan.2006.11.003
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发表时间：
2007-03-01
期刊：
影响因子：
5.3
通讯作者：
Dowlati, Afshin
中科院分区：
文献类型：
--
作者：
Cortas, Tania;Eisenberg, Rosana;Dowlati, Afshin
背景：免疫组化（IHC）检测EGFR总表达未能证实其预后重要性。我们假设，激活（磷酸化）状态的EGFR（p-EGFR）和其激活的下游信号通路（p-STAT-3）将有预后价值在NSCLC。方法：145例患者进行肺切除术，从1998年至2002年在大学医院的非小细胞肺癌。建立了TNM分期、性别、年龄、复发时间和生存率的数据库。通过IHC定量p-EGFR和p-STAT-3水平。将样本分为阴性、1+、2+或3+（分别为5- 19%、20- 50%、7> 50%的肿瘤细胞染色）。多因素分析采用考克斯比例风险模型。58%为女性，54%为腺癌。病理分期：Ⅰ期占54%，Ⅱ期占31%，Ⅲ期占15%。32%为p-EGFR阳性（鳞状36%，腺癌29%）。p-STAT-3染色见于38%，腺癌（46%）高于鳞状细胞（27%，p = 0.02），> 70岁患者高于< 70岁患者（p = 0.06）。存在p-EGFR和p-STAT-3共表达的趋势（p = 0.09）。EGFR和STAT-3激活与未激活患者5年生存率的Kaplan-Meier概率无显著差异。结论：EGFR在NSCLC中的表达率为70%，而p-EGFR仅在1/3的NSCLC患者中表达。p-EGFR和p-STAT-3通常在肿瘤中共表达，与肺癌中已知的信号转导途径相容。然而，EGFR和STAT-3激活状态不能提供切除疾病的预后信息。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Background: Total EGFR expression by immunohistochemistry (IHC) has failed to demonstrate prognostic importance. We hypothesized that activation (phosphorylated) state of EGFR (p-EGFR) and its activated downstream signal pathway (p-STAT-3) wilt have prognostic value in NSCLC.Methods: 145 patients underwent lung resection for NSCLC at University Hospitals from 1998-2002. A database with TNM stage, gender, age, time to recurrence, and survival was established. p-EGFR and p-STAT-3 levels were quantified by IHC. Specimens were divided into negative, 1+, 2+, or 3+ (5-19%, 20-50%7 > 50% of tumor cells staining respectively). Cox pro-portional hazard model was used for multivariate analysis.Results: Median age was 70 years. 58% were female and 54% had adenocarcinoma. Pathologic stage was as follows: stage 1: 54%, stage It: 31%, stage 111: 15%. 32% were positive for p-EGFR (squamous 36%, adenocarcinoma 29%). p-STAT-3 staining was seen in 38% and was higher in adenocarcinoma (46%) versus squamous cell (27%, p = 0.02) and was higher in patients > 70 years than compared to those < 70 years (p = 0.06). There was a trend toward co-expression of p-EGFR and p-STAT-3 (p = 0.09). The 5-year Kaplan-Meier probabilities of overall survival were not different amongst patients with activated versus no activation of EGFR and STAT-3.Conclusions: Although EGFR is commonly expressed in NSCLC (similar to 70%), p-EGFR is seen in only 1/3 of patients. p-EGFR and p-STAT-3 were commonly co-expressed in tumors compatible with known signal transduction pathways in lung cancer. However, EGFR and STAT-3 activation status does not provide prognostic information in resected disease. (c) 2006 Elsevier Ireland Ltd. All rights reserved.