Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib
Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib
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DOI：
10.1093/annonc/mdm003
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发表时间：
2007-04-01
影响因子：
50.5
通讯作者：
Bunn, P. A., Jr.
中科院分区：
文献类型：
--
作者：
Hirsch, F. R.;Varella-Garcia, M.;Bunn, P. A., Jr.
背景：晚期非小细胞肺癌(NSCLC)患者选择表皮生长因子受体(EGFR)靶向治疗的生物标志物尚未建立。患者和方法：采用FISH方法检测EGFR/HER2基因拷贝数，免疫组织化学方法检测EGFR蛋白和PACT表达，并检测EGFR和KRAS突变。结果：EGFR和HER2基因拷贝数(FISH+)、EGFR蛋白过表达(IHC+)、EGFR突变和PACT过表达均显著高于非小细胞肺癌患者(33%、29%、22%、39%和20%)。EGFR FISH+(32%)和IHC+(61%)与生存率提高有关，而EGFR突变(27%)、KRAS突变(26%)和PACK表达(69%)与生存率无关。在多因素生存分析中，EGFR、FISH和IHC是独立的预测指标。EGFR FISH+/IHC+患者(23%)的中位生存期为21个月，而双阴性患者(30%)的中位生存期为6个月。结论：联合应用EGFR FISH和IHC可有效预测吉非替尼的疗效。双阴性结果的患者不太可能在西部非小细胞肺癌人群中受益。
Background: Biological markers for optimal selection of patient to epidermal growth factor receptor (EGFR)-targeted therapies are not established in advanced non-small-cell lung cancer (NSCLC).Patients and methods: EGFR/HER2 gene copy number by FISH, EGFR protein and pAKT expression by immunohistochemistry (IHC) and EGFR and KRAS mutations were tested in 204 gefitinib-treated NSCLC patients.Results: Increased EGFR and HER2 gene copy number (FISH+), EGFR protein overexpression (IHC+), EGFR mutations and pAKT overexpression were all associated with significantly higher response rates (33%, 29%, 22%, 39% and 20% respectively). EGFR FISH+ (32%) and IHC+ (61%) correlated with improved survival, while EGFR mutations (27%), KRAS mutations (26%) and pAKT expression (69%) did not. In multivariate survival analysis EGFR FISH and IHC were independent predictive markers. EGFR FISH+/IHC+ patients (23%) had a median survival of 21 months versus 6 months for double-negative patients (30%).Conclusion: Combination of EGFR FISH and IHC is effective predictor for benefit from gefitinib. Patients with double-negative results are unlikely to benefit in western NSCLC populations.