气管腺样囊性癌表皮生长因子受体基因突变的检测

Detection of epidermal growth factor receptor in tracheal adenoid cystic carcinoma

目的了解气管腺样囊性癌肿瘤组织表皮生长因子受体（EGFR）18、19、20、21位点基因突变情况，为气管腺样囊性癌的分子靶向治疗奠定基础。方法将自2004年至2013年在煤炭总医院经气管镜下取出的气管腺样囊性癌共36例蜡块标本，提取肿瘤细胞DNA，采用ARMS法进行EGFRl8、19、20、21位点基因突变检测。采用Fisher精确概率法比较两组之间阳性率的差别。P〈0．05为差异有统计学意义。结果36例气管腺样囊性癌蜡块包埋标本中，EGFR基因突变阳性率为31％（11／36）。14％（5／36）存在双突变（19外显子缺失突变及21外显子突变），0％（0／36）出现EGFR基因20外显子突变。临床分期为Ⅳ期的标本EGFR基因突变率为63％（5／8），临床分期为Ⅱ～Ⅲ期的标本中EGFR基因突变率为21％（6／28），两组间有明显差异（P〈0．05）。结论气管腺样囊性癌EGFR基因突变率介于肺腺癌与鳞癌之间。气管腺样囊性癌EGFR基因突变在已有血行转移的患者中阳性率明显高于无血行转移者，晚期气管腺样囊性癌患者可能从EGFR-酪氨酸激酶抑制剂治疗中获益。

Objective To investigate the status of epidermal growth factor receptor （EGFR） gene mutations in exon 18,19,20, and 21 in tracheal adenoid cystic carcinoma, to experimentally explore thepotentiality of molecularly targeted therapy in this disease. Methods The tumor cell DNA was harvested for EGFR gene mutation detection in exon 18,19,20 ,and 21 by ARMS method, which was extracted fromparaffin embedded bronchoscopic biopsy specimens in 36 patients with adenoid cystic carcinoma at Meitan General Hospital from 2004 to 2013. The difference of mutation rate between groups was compared usingFisher＇s exact probability test. P 〈 0.05 was considered as statistical significance. Results The gene mutation rate of EGFR was 31 %（11/36） in the 36 paraffin embedded specimens of tracheal adenoid cysticcarcinoma. Among them, 14% （5/36） expressed double mutation （deletion in exon 19 and exon 21 mutation） ,0% （0/36） expressed mutation in exon 20. The EGFR geae mutation rate in stage IV groupwas 63 % （5/8）, while 21% （6/28） in stage Ⅱ - Ⅲ group. There was statistical significance between the two groups （ P 〈0.05）. Conclusions The EGFR gene mutation rate in tracheal adenoid cystic carcinomamay lie between that in lung adenocarcinoma and squamous cell carcinoma,which is slightly higher than that in squamous cell carcinoma. The EGFR mutation rate in patients with hematogenous metastatictumors is significantly higher than that in non-metastatic individuals. Patients with advanced tracheal adenoid cystic carcinoma may benefit from EGFR-tyrosine kinase inhibitor treatment.