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EGFRTKIs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EGFRTKIs治疗方面价值有限。
Objective 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.
作者
杜俊
邸婧
杨丽
刘畅
何磊
刘冬戈
王征
Du Jun;Di Jing;Yang Li;Liu Chang;He Lei;Liu Dongge;Wang Zheng(Department of Pathology,Beijing Hospital,National Center of Gerontology,Beijing 100730,China;Department of Oncology,PLA General Hospital,Beijing 100853,China)
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2019年第8期856-860,共5页
Chinese Journal of Geriatrics
基金
国家自然科学基金(81641114).
关键词
肺肿瘤
肿瘤转移
受体
表皮生长因子
DNA突变分析
Lung neoplasms
Neoplasm metastasis
Receptor, epidermal growth factor
DNA mutational analysis
