High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan
High frequency of epidermal growth factor receptor mutations with complex patterns in non-small cell lung cancers related to gefitinib responsiveness in Taiwan
复制标题
DOI：
10.1158/1078-0432.ccr-04-1245
复制
发表时间：
2004-12-15
影响因子：
11.5
通讯作者：
Tsai, SF
中科院分区：
文献类型：
--
作者：
Huang, SF;Liu, HP;Tsai, SF
目的：最近发现非小细胞肺癌中表皮生长因子受体（EGFR）突变与吉非替尼反应性相关。EGFR突变的检测已成为非小细胞肺癌治疗决策的重要问题。实验设计：对101例未接受吉非替尼治疗的患者的新鲜冷冻肿瘤组织和16例接受吉非替尼治疗的患者的parafrin包埋肿瘤组织进行EGFR编码序列激酶结构域的突变分析。用免疫印迹法检测冰冻肿瘤组织中磷酸化的EGFR。结果：101例非小细胞肺癌肿瘤标本中腺癌69例，鳞状细胞癌24例，其他非小细胞肺癌8例。在39例患者中发现了EGFR基因激酶结构域（外显子18至外显子21）的突变。所有的突变都发生在腺癌中，除了一个发生在腺鳞癌中。腺癌的突变率为55%（38 / 69）。在接受吉非替尼治疗的16名患者中，9名应答者中有7名有EGFR突变，7名无应答者中只有1名有突变，其中包括无义突变。突变似乎很复杂，总共观察到23种不同的突变，9个肿瘤携带2种突变。结论：我们的研究数据预测，吉非替尼在中国和其他东亚人群肺腺癌患者中的应答率更高。EGFR与腺癌的密切联系以及突变的高频率提高了EGFR突变在肺腺癌的发生中发挥重要作用的可能性，特别是在东亚地区。
Purpose: Epidermal growth factor receptor (EGFR) mutations related to gefitinib responsiveness in non-small cell lung cancer have been found recently. Detection of EGFR mutations has become an important issue for therapeutic decision-making in non-small cell lung cancer.Experimental Design: Mutational analysis of the kinase domain of EGFR coding sequence was done on 101 fresh frozen tumor tissues from patients without prior gefitinib treatment and 16 parafrin-embedded tumor tissues from patients treated with gefitinib. Detection of phosphorylated EGFR by immunoblot was also done on frozen tumor tissues.Results: The 101 non-small cell lung cancer tumor specimens include 69 adenocarcinomas, 24 squamous cell carcinomas, and 8 other types of non-small cell lung cancers. Mutation(s) in the kinase domain (exon 18 to exon 21) of the EGFR gene were identified in 39 patients. All of the mutations occurred in adenocarcinoma, except one that was in an adenosquamous carcinoma. The mutation rate in adenocarcinoma was 55% (38 of 69). For the 16 patients treated with gefitinib, 7 of the 9 responders had EGFR mutations, and only 1 of the 7 nonresponders had mutations, which included a nonsense mutation. The mutations seem to be complex in that altogether 23 different mutations were observed, and 9 tumors carried 2 mutations.Conclusions: Data from our study would predict a higher gefitinib response rate in lung adenocarcinoma patients in Chinese and, possibly, other East Asian populations. The tight association with adenocarcinoma and the high frequency of mutations raise the possibility that EGFR mutations play an important role in the tumorigenesis of adenocarcinoma of lung, especially in East Asians.