Predection for sensitivity of gefitinib against Non-small cell lung cancer

目得：吉非替尼是一种表皮生长因子受体（EGFR，HER 1/ErbB 1）酪氨酸激酶抑制剂，已显示出对非小细胞肺癌（NSCLC）的临床活性。本研究的目的是比较表皮生长因子受体家族（EGFR，HER 2，HER 3，HER 4）和EGFR基因突变的表达状态和临床反应gefitinib.PATIENTS和方法：晚期或复发性非小细胞肺癌患者与吉非替尼单药治疗的肺癌组织进行了分析。采用免疫组化（IHC）方法检测31例肿瘤组织中HER家族的表达，17例冰冻组织中采用PCR单链构象多态性（SSCP）分析EGFR基因突变。结果：EGFR阳性21例（68%），HER 2阳性24例（77%），HER 3阳性17例（55%），HER 4阳性4例（13%）。31例患者中有14例（45%）表现出EGFR和HER 2以及HER 3或HER 4的三重表达。观察到三重表达组的缓解率（RR）和进展时间（TTP）显著优于其他组（RR 50 vs 11% ; P<0.05，中位TTP 4.29 vs 1.2个月; P<0.05），尽管没有发现单个HER家族成员的表达状态存在差异。在17例冰冻肿瘤组织中发现6例EGFR突变（48%）。EGFR突变组6例均为HER家族三重表达，无突变组4例为HER家族三重表达，P= 0.011。结论：吉非替尼可联合作用于EFGR和HER 2及其他HER家族成员，为筛选治疗有效的患者提供了一种方法。

PURPOSE : Gefitinib is an inhibitor of the epidermal growth factor receptor (EGFR, HER1/ErbB1) tyrosine kinase that has shown clinical activity against non-small-cell lung cancer (NSCLC). The aim of the present study was to compare the relationship between expression status of HER family(EGFR, HER2,HER3,HER4) and EGFR gene mutations and clinical response to gefitinib.PATIENTS AND METHODS : Lung carcinoma tissues of advanced or recurrent NSCLC patients treated with monotherapy of gefitinib were analyzed. Expressions of HER family in 31 tumors were exmined by immunohistochemistry (IHC) and EGFR gene mutations were examined in 17 frozen tissues by PCR single-strand conformation polymorphism (SSCP) analysis. The medical records were reviewed for clinical variables.RESULTS : Total positivity rates were 21 for EGFR (68%), 24 for HER2 (77%), 17 for HER3 (55%) and 4 for HER4 (13%). Fourteen of 31 (45%) demonstrated triple expression of EGFR and HER2, as well as HER3 or HER4. A significantly better response rate (RR) and time to progression (TTP) were observed for the group with the triple expression than for the other groups (RR 50 vs 11% ; P<0.05, median TTP 4.29 vs 1.2 months ; P<0.05), although no difference was found with the expression status of individual HER family members. Six EGFR mutations were found in 17 frozen tumor tissues (48%). Triple expression of HER family were present in all 6 cases with EGFR mutations and in 4 of 11 cases without mutations ; P=.011.Conclusion : Gefitinib may act on EFGR and HER2 and other HER family members in combination, providing a means for selection of patients most likely to respond to therapy.