406例肺癌小活检标本中表皮生长因子受体基因的突变分析

目的探讨肺癌小活检标本中表皮生长因子受体（epidermal growth factor receptor,EGFR）基因的突变情况。方法采用蝎形探针扩增阻滞突变系统（Scorpions ARMS）检测406例肺癌小活检标本中EGFR基因第18、19、20和21外显子的突变情况。结果在406例肺癌小活检标本中,检测到190例存在EGFR突变（占46.8%）,其中80例为第19外显子框内多核苷酸缺失、88例为第21外显子L858R突变、4例为第21外显子L861Q突变、9例为第18外显子G719X突变、2例为第20外显子S768I突变、1例为第20外显子T790M突变;此外,发现6例存在双位点突变。肺腺癌EGFR突变率为55.5%（186/335）,鳞状细胞癌突变率为5.8%（3/52）,5例腺鳞癌中有1例检测到EGFR基因突变,其它类型肺癌均未检测到EGFR基因突变（0/14）。女性患者EGFR基因突变率（62.4%）明显高于男性患者（32.1%,P〈0.01）,非吸烟患者EGFR基因突变率（59.8%）明显高于吸烟患者（24.7%,P〈0.01）。结论 EGFR基因突变多见于女性、非吸烟和肺腺癌患者;Scorpions ARMS是检测活检小标本EGFR基因突变的可靠方法。

Analysis of epidermal growth factor receptor gene mutations in 406 small biopsy samples of lung cancer

Objective To investigate the mutations of epidermal growth factor receptor （EGFR）gene in small biop-sy samples of lung cancer.Methods Mutations of EGFR gene （exons18,19,20 and 21）in small biopsy specimens from 406 cases of lung cancer were detected by scorpions amplification refractory mutation system （Scorpions ARMS）.Re-sults EGFR gene mutations were identified in 190 of 406 （46.8%）small biopsy samples of lung cancer.In-frame dele-tions of exon 19 occurred in 80 patients and point mutation occurred at codon 858,861（exon 21）in 88 and 4 patients re-spectively.Nine patients had mutation at codon 719x （exon18）.Two patients had point mutation occurring at codon 768 （exon 20）and one patient had point mutation occurring at codon 790 （exon 20）.In addition,six patients had compound mutations.Mutations were present in 55.5% of 335 adenocarcinoma and in 5.8% of 52 squamous carcinoma.EGFR mutation was found in 1 of 5 adenosquamous carcinoma.There were no EGFR mutation in other type of lung cancer（0/14）.EGFR mutation rate was higher in female patients and patients without smoking history than male patients and pa-tients with smoking history（P〈0.01,respectively）.Conclusion EGFR mutations were more common in female,non-smoking patients with adenocarcinoma histology.Scorpions ARMS assay is a reliable,specifical and sensitive method for the detection of EGFR kinase domain mutations in small biopsy samples.