非小细胞肺癌原发灶与脑转移灶EGFR基因突变状况的一致性研究

目的 探讨非小细胞肺癌（NSCLC）原发灶与脑转移灶的表皮生长因子受体（EGFR）基因突变状况，分析两者之间是否存在一致性。方法 收集2003年1月至2011年12月31例NSCLC脑转移患者的肺原发灶和脑转移灶石蜡包埋组织标本，应用DNA直接测序法进行EGFR突变分析，如发现两者突变不一致则进一步采用增殖阻碍突变系统 （ARMS）验证。结果 31例NSCLC肺原发灶中，8例存在19外显子E746-A750缺失突变、4例为21外显子L858R点突变；在31例脑转移灶样本中，8例为19外显子E746-A750缺失突变，3例存在21外显子L858R点突变，EGFR突变类型在脑转移灶和肺原发灶的分布差异无统计学意义 （P=0.793）。共有16.1％ （5／31）的肺原发灶和脑转移灶EGFR突变状况不一致，其中男性4例，女性1例；3例腺癌 （2例脑转移灶19外显子缺失突变而肺原发灶阴性突变，1例肺原发灶21外显子点突变而脑转移灶阴性突变），1例鳞癌和1例非典型类癌 （均为脑转移灶阴性突变而肺原发灶19外显子缺失突变）。结论 NSCLC原发病灶及脑转移灶EGFR基因突变存在不一致性。

Consistency of EGFR mutations between primary and brain metastatic tumors in non-small cell lung cancer

Objective To invistigate the discordance of epidermal growth factor receptor（EGFR） mutations between primary and brain metastatic tumors in non-small cell lung cancer（NSCLC）,and then analyze the consistency between them.Methods Thirty-one paired primary and brain metastatic tumors colleted from Jan.2003 to Dec.2011 were evaluated for the EGFR mutation by direct DNA sequencing and the cases of discordance of EGFR mutation were further detected by amplifyication refractory mutation system （ARMS）.Results In 31 case of primary tumors,8 presented with deletions in exon 19 and 4 presented with L858R （leucine to arginine at codon 858） mutation in exon 21.In 31 case of brain metastatic tumors,8 presented with deletions in exon 19 and 3 presented with L858R （leucine to arginine at codon 858） mutation in exon 21.There was no difference in distribution between the primary and brain metastatic tumors in NSCLC （P =0.793）.However,contrasted the primary and brain metastatic tumors individual through the ARMS,we found the EGFR gene mutation types were discordant in 5（16.1％） patients （4 male and 1 female）,including 3 adenocarcinoma （the brain metastatic tumors presented with deletions in exon 19 while the primary tumors presented with no EGFR gene mutation in 2 patients,and the primary tumor presented with L858R mutation in exon 21 while the brain metastatic tumor presented with no EGFR gene mutation in 1 patient）,1 squamous-cell carcinoma and 1 atypical carcinoid （the primary tumors presented with deletions in exon 19 while the brain metastatic tumors presented with no EGFR gene mutation in both patients）.Conclusion EGFR mutations show discordance between the primary and the brain metastatic tumors in NSCLC.