非小细胞肺癌组织EGFR/ALK/ROS1基因联合检测的临床意义

Clinical Significance of Combined Detection of EGFR/ALK/ROS1 Genes in Non-Small Cell Lung Cancer

目的探讨非小细胞肺癌(NSCLC)患者表皮生长因子受体(EGFR),间变性淋巴瘤激酶(ALK)和肉瘤致癌因子-受体酪氨酸激酶(ROS1)三种基因突变联合检测的临床意义。方法收集2017年1月～2018年7月患者NSCLC组织标本146例,采用过柱法提取DNA和RNA,突变检测采用RT-PCR法和扩增阻滞突变系统(ARMS)法。结果EGFR/ALK/ROS1三联检的突变频率为41.8%(61/146),明显高于单基因检测突变率:EGFR (33.6%,49/146),ALK(6.8%,10/146)和ROS1(2.7%,4/146)。EGFR的不同突变类型的检出率如下:19Del 52.9%(27/51),L858R41.2%(21/51),G719X,L861Q5.9%(3/51);其中还检出四例双突变标本:19Del+L858R(1例),19Del+G719X,L861Q(1例),ALK+19Del(1例),ROS1+L858R(1例)。EGFR/ALK/ROS1阳性标本中女性(56.7%,30/53)明显高于男性(33.3%,31/93),两者比较差异有统计学意义(χ~2=7.516,P=0.006),肺腺癌(47.9%,58/121)明显高于鳞癌(4.8%,1/21),差异具有统计学意义(χ~2=13.733,P=0.000)。不同来源组织突变检出率为:手术切除肿瘤组织标本41.0%(32/78),细针穿刺活检及支气管镜刷检细胞学等标本43.4%(23/53),胸腔积液标本40.0%(6/15),三者比较差异无统计学意义(P>0.05)。结论在NSCLC基因突变中:EGFR/ALK/ROS1三联检的突变频率明显高于EGFR,ALK和ROS1单基因检测。EGFR常见突变基因为19Ex Del和21Ex L858R。女性突变率明显高于男性。EGFR/ALK/ROS1的联合检测可一次获得更多基因突变信息,为靶向用药提供更多选择,尤其是对于临床稀有标本意义更大。

Objective To explore the clinical significance of combined detection of three gene mutations in non small cell lung cancer （NSCLC） patients：epidermal growth factor receptor （EGFR） ,mesenchymal lymphoma kinase （ALK） and sarcomao ncogene receptor tyrosine kinase （ROS1）. Methods From January 2017 to July 2018,146 patients with NSCLC tissue were collected in Shaanxi Province People＇s Hospital. DNA and RNA were extracted by centrifugal mini column methods. RT PCR and amplification block mutation system （ARMS） method were employed in the mutation detection. Results The gene mutation rate of EGFR/ALK/ROS1 （41.8% , 61/146） was significantly higher than that of EGFR （33.6%, 49/146）, ALK （6.8G, 10/146） and ROSI （2.7%, 4/146）. The mutation rate of different mutation types of EGFR gene were as follows： deletions at exon 19 was 52.9% （27/51） ,21Ex L858R was 41.2% （21/51） ,18Ex G719X,21Ex L861Q was 5.9% （3/51） ; Also co mutation of 19 Del＋ L858R （1 sample）,19Del＋ G719X,L861Q （1 sample）,ALK＋19 Del （1 sample）,and ROS1 ＋L858R （1 sample） in EGFR were detected. Among EGFR/ALK/ROS1 positive samples, women （56.7% , 30/53） were higher than men （33.3% , 31/93）, the comparison was statistically significant （ x2= 7.516, P= 0.006）, and lung adenoearei noma （47.9% , 58/121） was significantly higher than squamous cancer （4.8% ,1/21）, the comparison was statistically sig nificant （x2=13. 733, P=0. 000）. The mutation detection rate of different source organizations were as follows：large tissue specimens （41.0 %, 32/78） , fine needle biopsy and bronehoseopie brush cytology （43.4% , 23/53）, and pleural water speei mens （40.0% ,6/15）. Conclusion In the NSCLC gene mutation,the mutation frequency of EGFR/ALK/ROS1 was signifi candy higher than that of EGFR,ALK and ROS1 gene detection, and the common mutation genes of EGFR were 19Ex Del and 21Ex L858R. Female mutation rate was significantly higher than male. The combined detection of EGFR/ALK/ROS1 can obtain more information of gene mutation at one time, providing more choices for targeted drugs, especially for rare clinical specimens.