Onn Amir, Correa Arlene M, Gilcrease Michael, Isobe Takeshi, Massarelli Erminia, Bucana Corazon D, O'Reilly Michael S, Hong Waun K, Fidler Isaiah J, Putnam Joe B, Herbst Roy S
Department of Thoracic, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):136-43. doi: 10.1158/1078-0432.ccr-0373-3.
Despite maximal therapy, surgically treated patients with stage I non-small cell lung cancer (NSCLC) are at risk for developing metastatic disease. Histopathologic findings cannot adequately predict disease progression, so there is a need to identify molecular factors that serve this purpose. Because the ErbB receptors play an important role in lung cancer progression, we analyzed the expression of epidermal growth factor receptor (EGFR), phosphorylated EGFR, transforming growth factor alpha (TGFalpha), and HER2-neu as potential prognostic factors in stage I NSCLC.
Using immunohistochemical techniques, we retrospectively analyzed formalin-fixed, paraffin-embedded samples from 111 patients with resected pathological stage I NSCLC. Then we correlated these data with patient clinical outcome.
Median follow-up was 69.3 months. EGFR overexpression (defined as >10% membranous staining) was found in 66 tumors (59.5%). It was significantly more common in T(2) tumors than in T(1) tumors (P = 0.001), and in more squamous cell carcinomas than in adenocarcinomas (P = 0.07). HER2-neu overexpression was found in 19 tumors (17.1%) and was significantly more common in adenocarcinomas than in squamous cell carcinomas (P = 0.035). Synchronous overexpression of EGFR and HER2-neu was found in 11 tumors (9.9%). Patients with these tumors had a significantly shorter time to recurrence (P = 0.006) and a trend toward shorter overall survival (P = 0.093). Phosphorylated EGFR and transforming growth factor alpha were detected but were not related to prognosis.
Synchronous overexpression of EGFR and HER2-neu at the protein level predicts increased recurrence risk and may predict decreased survival in patients with stage I NSCLC. This suggests that important interactions take place among the different members of the ErbB family during tumor development and suggests a method for choosing targeted therapy. A prospective study is planned.
尽管采取了最大限度的治疗措施，但接受手术治疗的Ⅰ期非小细胞肺癌（NSCLC）患者仍有发生转移性疾病的风险。组织病理学检查结果无法充分预测疾病进展，因此有必要确定能够发挥此作用的分子因素。由于表皮生长因子受体（ErbB）在肺癌进展中起重要作用，我们分析了表皮生长因子受体（EGFR）、磷酸化EGFR、转化生长因子α（TGFα）和HER2-neu的表达，将其作为Ⅰ期NSCLC潜在的预后因素。
我们采用免疫组织化学技术，回顾性分析了111例接受手术切除的病理Ⅰ期NSCLC患者的福尔马林固定、石蜡包埋样本。然后将这些数据与患者的临床结局进行关联分析。
中位随访时间为69.3个月。在66例肿瘤（59.5%）中发现EGFR过表达（定义为膜染色>10%）。在T(2)肿瘤中比在T(1)肿瘤中更常见（P = 0.001），在鳞状细胞癌中比在腺癌中更常见（P = 0.07）。在19例肿瘤（17.1%）中发现HER2-neu过表达，在腺癌中比在鳞状细胞癌中更常见（P = 0.035）。在11例肿瘤（9.9%）中发现EGFR和HER2-neu同步过表达。这些肿瘤患者的复发时间明显缩短（P = 0.006），总生存期有缩短趋势（P = 0.093）。检测到磷酸化EGFR和转化生长因子α，但与预后无关。
EGFR和HER2-neu在蛋白水平的同步过表达预示Ⅰ期NSCLC患者复发风险增加，可能预示生存期缩短。这表明在肿瘤发生发展过程中，ErbB家族不同成员之间发生了重要的相互作用，并提示了一种选择靶向治疗的方法。计划开展一项前瞻性研究。
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