摘要目的 通过建立液体活检技术检测肺腺癌脑脊液标本(CSF)表皮生长因子受体(EGFR)基因突变检测流程,研究肺腺癌脑转移患者EGFR基因突变检测模式并分析检测结果在临床治疗中的可能价值. 方法 回顾性研究,收集26例携带EGFR基因敏感突变(L858R突变和19号外显子缺失突变)肺腺癌患者CSF标本,肺腺癌患者均经一代EGFR小分子抑制剂(EGFR-TKIs)治疗后进展,影像学提示脑转移.同时收集5例临床和病理细胞学证实为非肿瘤患者CSF标本.应用本研究建立的CSF标本液体活检检测流程对无细胞上清标本进行EGFR基因突变检测. 结果 80.8％(21/26)肺腺癌患者CSF无细胞上清标本检测到EGFR敏感突变,13例(61.9％)21号外显子L858R位点突变,8例(38.1％)19号外显子缺失突变.所有CSF无细胞上清标本均未检测出T790M位点突变.5例非肿瘤患者CSF标本均未检测出EGFR基因突变. 结论 应用本研究建立的液体活检检测流程可完成CSF无细胞上清标本EGFR基因突变检测,且检测灵敏度和特异性较高.可能由于一代EGFR TKIs药物特点,耐药后脑转移CSF标本中T790M检出率低,CSF标本检测T790M位点突变在指导临床应用三代EGFR TKIs治疗方面价值有限.

abstractsObjective To study the detection protocol of epidermal growth factor receptor (EGFR)gene mutations in cerebrospinal fluid(CSF)specimens of lung adenocarcinoma by establishing a liquid biopsy technique,and to analyze clinical value of the detection findings for clinical therapy.Methods In the retrospective study,a total of 26 CSF specimens from lung adenocarcinoma patients who harbored EGFR gene mutations(L858R and EGFR exon 19 deletion)were collected.The included patients were treated with first-generation EGFR TKIs,and had brain metastasis detected by imaging examinations.Five CSF specimens from non-tumor patients confirmed by clinical findings and cytological and pathological diagnosis were collected during the same period.EGFR gene mutations in cell-free CSF supernatant fluid were detected by using the protocol recommended in this study.Results EGFR mutations were detected in 21/26 (80.8％)of cell-free supernatants from CSF specimens of lung adenocarcinoma patients,including 13 cases(61.9％)with EGFR L858R mutations and 8 cases(38.1％)with EGFR exon 19 deletion.No T790M mutation was detected in cell-free supernatants from all CSF specimens.No EGFR mutation was detected in cell-free supernatants from all CSF specimens from non-tumor patients.Conclusions Our study-established protocol could be used to detect EGFR mutations in cell-free supernatants from CSF specimens with high sensitivity and specificity.Perhaps due to the characteristics of first-generation EGFR TKIs,the detection rate of T790M mutation is low.The detection of T790M mutation in cell-free supernatants from CSF specimen may have a limited clinical value for choice of 3rd generation EGFR TKIs.