Epidermal growth factor receptor gene amplification and gefitinib sensitivity in patients with recurrent lung cancer
Epidermal growth factor receptor gene amplification and gefitinib sensitivity in patients with recurrent lung cancer
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DOI：
10.1007/s00432-007-0320-z
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发表时间：
2008-05-01
影响因子：
3.6
通讯作者：
Fujii, Yoshitaka
中科院分区：
文献类型：
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作者：
Sasaki, Hidefumi;Endo, Katsuhiko;Fujii, Yoshitaka
为了评估表皮生长因子受体（EGFR）蛋白表达，基因突变和扩增作为接受吉非替尼的非小细胞肺癌（NSCLC）患者临床结局的预测因子，我们进行了荧光原位杂交（FISH）和免疫组化（IHC）。我们研究了27例手术治疗的非小细胞肺癌（NSCLC）患者的EGFR扩增和EGFR蛋白表达状态。这些患者在手术后复发，并接受吉非替尼250 mg/天。通过基因分型分析和测序分析激酶结构域的EGFR突变的存在或不存在，并且已经报道。27例肺癌患者中有15例发现EGFR突变。EGFR突变状态与较好的预后显著相关（log-rank检验P = 0.0023）。吸烟状态（从不吸烟者vs.吸烟者，P = 0.0032）和病理亚型（腺癌vs.非腺癌，P = 0.0011）与肺癌生存率相关，但EGFR扩增（P = 0.1278）与肺癌生存率无关。EGFR IHC结果与FISH结果相关（P = 0.0125），但与预后无关（P = 0.7921）。因此，EGFR基因扩增或蛋白表达不是吉非替尼在日本NSCLC患者中疗效的预测因子。我们还评估了在国立医院组织近畿中央胸部医疗中心接受手术后接受吉非替尼治疗的27例NSCLC患者的EGFR突变状态和临床病理特征。EGFR基因突变状态，尤其是外显子19突变与吉非替尼疗效的相关性高于外显子21点突变。
To evaluate the epidermal growth factor receptor (EGFR) protein expression, gene mutations and amplification as predictors of clinical outcome in patients with non-small-cell lung cancer (NSCLC) receiving gefitinib, we have performed fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). We investigated the EGFR amplification and EGFR protein expression statuses in 27 surgically treated non-small-cell lung cancer (NSCLC) cases. These patients experienced relapse after surgery and received gefitinib 250 mg/day. The presence or absence of EGFR mutations of kinase domains was analyzed by genotyping analysis and sequences, and already reported. EGFR mutations were found from 15/27 lung cancer patients. EGFR mutation status was significantly correlated with better prognosis (log-rank test P = 0.0023). Smoking status (never smoker vs. smoker, P = 0.0032), and pathological subtypes (adenocarcinoma vs. non-adenocarcinoma, P = 0.0011), but not EGFR amplification (P = 0.1278), were correlated with survival of lung cancers. EGFR IHC results were correlated with FISH results (P = 0.0125), but not correlated with prognosis (P = 0.7921). Thus, the EGFR gene amplification or protein expression is not a predictor of gefitinib efficacy in Japanese patients with NSCLC. We have also evaluated the EGFR mutation status and clinico-pathological features for 27 NSCLC patients who had undergone surgery followed by treatment with gefitinib at the National Hospital Organization, Kinki-chuo Chest Medical Center. The EGFR mutation status, especially exon19 mutation was correlated with good response to gefitinib than exon 21 point mutation.