Cortas Tania, Eisenberg Rosana, Fu Pingfu, Kern Jeffrey, Patrick Lauren, Dowlati Afshin
From the Department of Medicine, Divisions of Hematology/Oncology, Case Comprehensive Cancer Center, Case Western Reserve University and University Hospitals of Cleveland, OH 44106, United States.
Lung Cancer. 2007 Mar;55(3):349-55. doi: 10.1016/j.lungcan.2006.11.003. Epub 2006 Dec 8.
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) will have prognostic value in NSCLC.
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%, >50% of tumor cells staining respectively). Cox proportional hazard model was used for multivariate analysis.
Median age was 70 years. 58% were female and 54% had adenocarcinoma. Pathologic stage was as follows: stage I: 54%, stage II: 31%, stage III: 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.
Although EGFR is commonly expressed in NSCLC ( approximately 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.
免疫组织化学（IHC）检测的总表皮生长因子受体（EGFR）表达未能显示出预后重要性。我们推测EGFR的激活（磷酸化）状态（p-EGFR）及其激活的下游信号通路（p-STAT-3）在非小细胞肺癌（NSCLC）中具有预后价值。
1998年至2002年期间，145例患者在大学医院接受了NSCLC肺切除术。建立了一个包含TNM分期、性别、年龄、复发时间和生存情况的数据库。通过IHC对p-EGFR和p-STAT-3水平进行定量。标本分为阴性、1+、2+或3+（分别为5%-19%、20%-50%、>50%的肿瘤细胞染色）。采用Cox比例风险模型进行多变量分析。
中位年龄为70岁。58%为女性，54%为腺癌。病理分期如下：I期：54%，II期：31%，III期：15%。32%的患者p-EGFR呈阳性（鳞状细胞癌为36%，腺癌为29%）。38%的患者可见p-STAT-3染色，腺癌（46%）高于鳞状细胞癌（27%，p=0.02），70岁以上患者高于70岁以下患者（p=0.06）。p-EGFR和p-STAT-3存在共表达趋势（p=0.09）。EGFR和STAT-3激活与未激活的患者之间，5年总体生存的Kaplan-Meier概率无差异。
虽然EGFR在NSCLC中普遍表达（约70%），但仅1/3的患者可见p-EGFR。p-EGFR和p-STAT-3在与肺癌已知信号转导通路相符的肿瘤中通常共表达。然而，EGFR和STAT-3激活状态并不能为切除疾病提供预后信息。
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