晚期肺腺癌血浆与组织表皮生长因子受体基因突变检测及预后分析

Comparison of EGFR mutation status of plasma with tissue in advanced pulmonary adenocarcinoma

目的针对晚期肺腺癌肿瘤组织标本与血浆标本表皮生长因子受体(EGFR)基因突变检测,了解EGFR基因检测结果对临床治疗的影响。方法前瞻性收集160例晚期肺腺癌患者肿瘤组织标本和血浆标本,采用扩增受阻突变系统(ARMS)法检测EGFR基因突变状态。结果肺腺癌组织标本中,EGFR基因突变率为50.6%,单突变78例(其中19del 42例,L858R 36例),双突变3例。血浆标本中,EGFR基因突变率为31.2%,单突变49例(其中19del 25例,L858R 23例,G719x 1例),双突变1例。ARMS法检测结果显示,两种标本均检测到突变者47例,均无突变者76例。组织标本检测到突变而血浆标本未检测到突变的有34例,反之有3例。两者检测一致率为76.9%,血浆EGFR检测的敏感性为58.0%,特异性为96.2%,阳性预测值为94.0%,阴性预测值为69.1%。结论晚期肺腺癌中EGFR基因突变肿瘤组织标本的检出率高于血浆标本,ARMS法血浆标本EGFR基因突变阳性结果可信性高,但突变阴性结果可靠性不高,对无法取得组织活检的患者血浆检测可作为补充手段。

Objective To observe the clinical significance of epithelial growth factor receptor(EGFR) mutations in tissue and plasma samples with advanced pulmonary adenocarcinoma. Methods Tumor tissues and plasma samples were collected from 160 patients with advanced pulmonary adenocarcinoma and the EGFR mutation status was detected by amplification refractory mutation system(ARMS). Results In pulmonary adenocarcinoma tissue samples, 50.6% exhibited EGFR mutations, and among them 78 samples exhibited single mutations, which included 42 of 19 del mutation, and 36 of L858 R mutation. The remaining three EGFR mutant tissue samples exhibited double mutation. However, in plasma samples test, 31.2% exhibited EGFR mutations. Among these mutant samples, 49 samples had single mutation, which included 25 samples of 19 del mutation, 23 samples of L858 R mutation and 1 sample of G719x mutation, one EGFR mutant plasma sample exhibited double mutation. The results from ARMS method showed that 47 cases exhibited mutations and 76 cases exhibited no mutations in both tissue samples and the plasma samples. In 34 cases, mutations were only detected in tumor tissue samples but not in the plasma samples, and in three cases, mutations were only detected in plasma samples but not in the tumor tissue samples. The overall concordance of EGFR mutations between tissue and plasma samples was 76.9%. The sensitivity and specificity of the EGFR detection using plasma samples were 58.0% and 96.2%, respectively. The predictive values of EGFR positive and negative samples were 94.0% and 69.1%, respectively. Conclusion In advanced pulmonary adenocarcinoma, the detection rate of EGFR mutations in tumor tissue samples is higher than that in plasma samples. Using the ARMS method is reliable for the EGFR mutations positive plasma samples, but the reliability of mutation negative is not high, and it can be used as a supplementary means for patients who can not obtain tissue biopsy.