Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer
Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer
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DOI：
10.1093/jnci/dji112
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发表时间：
2005-05-04
影响因子：
10.3
通讯作者：
Varella-Garcia, M
中科院分区：
文献类型：
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作者：
Cappuzzo, F;Hirsch, FR;Varella-Garcia, M
背景：吉非替尼是表皮生长因子 (EGFR) 酪氨酸激酶的选择性抑制剂，该激酶在许多癌症中过度表达，包括非小细胞肺癌 (NSCLC)。我们开展了一项临床研究，比较 EGFR 基因拷贝数、EGFR 蛋白表达、EGFR 突变和 Akt 激活状态之间的关系，作为晚期 NSCLC 吉非替尼治疗的预测标志物。方法：通过荧光原位杂交 (FISH)、DNA 测序和免疫组织化学评估每天接受 250 mg 吉非替尼治疗的 102 名 NSCLC 患者的肿瘤的 EGFR 状态，并通过免疫组织化学评估 Akt 激活状态（磷酸化 Akt [P-Akt]）。通过 Kaplan-Meier 方法计算和评估进展时间、总生存率和 95% 置信区间 (CI)；使用对数秩检验对各组进行比较。使用 Cox 比例风险回归模型和多变量分析评估与生存相关的风险因素。所有统计检验都是双面的。结果：EGFR 基因的扩增或高度多体性（见于 102 名患者中的 33 名）和高蛋白表达（见于 98 名患者中的 58 名）在统计上与更好的反应显着相关（36% 与 3%，平均差异 = 34%，95% CI = 16.6 至 50.3；P
Background: Gefitinib is a selective inhibitor of the epidermal growth factor (EGFR) tyrosine kinase, which is overexpressed in many cancers, including non-small-cell lung cancer (NSCLC). We carried out a clinical study to compare the relationship between EGFR gene copy number, EGFR protein expression, EGFR mutations, and Akt activation status as predictive markers for gefitinib therapy in advanced NSCLC. Methods: Tumors from 102 NSCLC patients treated daily with 250 mg of gefitinib were evaluated for EGFR status by fluorescence in situ hybridization (FISH), DNA sequencing, and immunohistochemistry and for Akt activation status (phospho-Akt [P-Akt]) by immunohistochemistry. Time to progression, overall survival, and 95% confidence intervals (CIs) were calculated and evaluated by the Kaplan-Meier method; groups were compared using the log-rank test. Risk factors associated with survival were evaluated using Cox proportional hazards regression modeling and multivariable analysis. All statistical tests were two-sided. Results: Amplification or high polysomy of the EGFR gene (seen in 33 of 102 patients) and high protein expression (seen in 58 of 98 patients) were statistically significantly associated with better response (36% versus 3%, mean difference = 34%, 95% CI = 16.6 to 50.3; P