CAJ | 학술논문

背景与目的:表皮生长因子受体(epidermal growth factor receptor,EGFR)基因的突变状态与肺癌患者应用EGFR酪氨酸激酶抑制剂(EGFR-tyrosine kinase inhibitors,EGFR-TKIs)的疗效密切相关.目前,临床上缺乏统一的方法检测EGFR基因突变.本研究旨在探讨直接测序法与蝎形探针扩增阻滞突变系统(scorpions amplification refractory mutation system,scorpions ARMS法)在检测肺癌临床活检小标本EGFR突变时敏感性的差异,以及相关靶向治疗疗效的分析.方法:采用直接测序法和ARMS法共同检测168例石蜡包埋肺癌标本,并随访评估其中行靶向治疗患者的临床疗效.结果:手术标本80例中,直接测序法与ARMS法所检出的突变阳性率分别为18.8%和25.0%,敏感性分别为71.4%和95.2%,差异无统计学意义(P>0.05).而活检小标本88例中,直接测序法与ARMS法所检出的突变阳性率分别为19.3%和42.0%,敏感性分别为42.5%和92.5%,前者均显著低于后者(P<0.01).靶向治疗疗效方面,直接测序法与ARMS法野生型患者客观缓解率(objective response rate,ORR)分别为26.3%和3.8%,前者明显高于后者(P<0.05),而在小活检标本中,直接测序法野生型患者ORR达32.0%.直接测序法野生型患者中位无进展生存期(progression-free survival,PFS)为4.0个月,明显长于ARMS法野生型患者的1.5个月(P<0.05).结论:对活检小标本而言,ARMS法较直接测序法的敏感性更高,其检测结果与临床疗效的一致性更好,纤维支气管镜活检等小标本EGFR突变检测更适合用ARMS法.
배경여목적:표피생장인자수체(epidermal growth factor receptor,EGFR)기인적돌변상태여폐암환자응용EGFR락안산격매억제제(EGFR-tyrosine kinase inhibitors,EGFR-TKIs)적료효밀절상관.목전,림상상결핍통일적방법검측EGFR기인돌변.본연구지재탐토직접측서법여갈형탐침확증조체돌변계통(scorpions amplification refractory mutation system,scorpions ARMS법)재검측폐암림상활검소표본EGFR돌변시민감성적차이,이급상관파향치료료효적분석.방법:채용직접측서법화ARMS법공동검측168례석사포매폐암표본,병수방평고기중행파향치료환자적림상료효.결과:수술표본80례중,직접측서법여ARMS법소검출적돌변양성솔분별위18.8%화25.0%,민감성분별위71.4%화95.2%,차이무통계학의의(P>0.05).이활검소표본88례중,직접측서법여ARMS법소검출적돌변양성솔분별위19.3%화42.0%,민감성분별위42.5%화92.5%,전자균현저저우후자(P<0.01).파향치료료효방면,직접측서법여ARMS법야생형환자객관완해솔(objective response rate,ORR)분별위26.3%화3.8%,전자명현고우후자(P<0.05),이재소활검표본중,직접측서법야생형환자ORR체32.0%.직접측서법야생형환자중위무진전생존기(progression-free survival,PFS)위4.0개월,명현장우ARMS법야생형환자적1.5개월(P<0.05).결론:대활검소표본이언,ARMS법교직접측서법적민감성경고,기검측결과여림상료효적일치성경호,섬유지기관경활검등소표본EGFR돌변검측경괄합용ARMS법.
@@@@Background and purpose:Somatic mutations in the epidermal growth factor receptor (EGFR) gene have been identified as a major determinant of the response to the treatment with EGFR-tyrosine kinase inhibitors (TKIs) in patients with lung cancer. At present, there is still no unified method to detect EGFR mutations in clinical practice. This study aimed to investigate the sensitivity of scorpions amplification refractory mutation system (Scorpions ARMS) in comparing with that of direct DNA sequencing in the detection of EGFR gene mutations in lung cancer clinical biopsy samples, and its correlation with clinical outcomes of EGFR tyrosine kinase inhibitors (EGFR-TKIs)therapy. Methods:Direct sequencing and ARMS were used simultaneously to detect EGFR mutation status in 168 formalin-fixed and parrffin-embeded (FFPE) lung cancer specimens, and the patients’ efficacy to TKIs was evaluated. Results:In 80 surgical excision samples, EGFR mutations were identified in 20 cases with a mutation rate of 25%by ARMS, while in 15 cases with a mutation rate of 18.8%by direct sequencing. Besides, the sensitivity of ARMS in surgical excision samples was 95.2%and that of direct sequencing was 71.4%. Neither mutation rate nor sensitivity between two methods showed statistical differences in the detection of surgical excision samples. In 88 biopsy samples, somatic mutations were identified in 37 cases with a mutation rate of 42.0% by ARMS, while in 17 cases with a mutation rate of 19.3%by direct sequencing. In addition, the sensitivity of ARMS in biopsy specimens was 92.5%and that of direct sequencing was 42.5%. There were significant differences of both mutation rate and sensitivity between two methods in the detection of biopsy samples (P<0.01). Among the patients receiving TKI therapy, objective response rate (ORR) of EGFR wild-type detected by direct sequencing was much higher than that of wild-type detected by ARMS (26.3%, 3.8%, respectively, P<0.05). The median progression-free survival (PFS) of patients with EGFR wild-type detected by direct sequencing was significantly longer than that of patients with wild-type detected by ARMS (4.0 months vs 1.5 months, P<0.05). Conclusion:Compared to direct sequencing, ARMS gains a higher sensitivity in the detection of EGFR mutations in clinical biopsy samples, and the results from ARMS are more consistent to the efficacy of TKI treatment.