非小细胞肺癌患者ALK,EGFR及KRAS基因的检测及临床病理特征

目的:研究汉族非小细胞肺癌患者中间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)、表皮生长因子受体(epidermal growth factor receptor,EGFR)及Kirsten鼠肉瘤基因(Kirstenrat sarcoma,KRAS)突变的阳性率及其与临床病理特征的关系.方法:采用免疫组织化学(immunohistochemistry,IHC)的方法检测ALK融合基因异常表达,采用PCR检测EGFR基因和KRAS基因突变,采用x2检验及Fisher精确概率法进行数据分析.结果:共2 267例进行了ALK融合基因检测,其中1 655例同时进行了EGFR突变检测,951例同时进行了KRAS检测.ALK融合基因、EGFR基因及KRAS基因突变阳性率分别为7.28％(165/2 267)、48.58％(804/1 655)、11.40％(108/947).ALK基因突变多见于年轻、腺癌患者;EGFR基因突变多见于女性、腺癌患者;KRAS基因突变多见于老年、男性、腺癌患者.1 655例同时进行了ALK与EGFR检测的病例中,共6例存在双基因突变(0.36％);947例同时进行了ALK与KRAS检测,共4例存在双基因突变(0.42％);943例同时进行了EGFR与KRAS突变检测,未发现双突变病例.结论:非小细胞肺癌患者ALK,EGFR和KRAS基因的突变与患者的年龄、性别、组织学类型均存在相应的联系,个别病例可以出现ALK融合基因与EGFR或KRAS突变共存.

Detection and clinicopathological features of ALK,EGFR and KRAS in non-small cell lung cancer patients

Objective:To investigate the mutation frequency of anaplastic lymphoma kinase (ALK) fusion gene,epidermal growth factor receptor (EGFR) gene,and Kirsten rat sarcoma (KRAS) gene in Han patients with non-small cell lung cancer and their relationship with clinical pathological features.Methods:The ALK fusion gene abnormal expression was detected by IHC;the EGFR and KRAS gene mutation status were detected by PCR.The data were analyzed by X2 test and Fisher's exact probability method.Results:A total of 2 267 cases were examined for ALK fusion gene.Among the total sample population,1 655 cases were simultaneously examined for EGFR mutation,951 cases among 2 267 were tested by KRAS.The mutation frequency of ALK fusion gene,EGFR gene and KRAS gene were 7.28％ (165/2 267),48.58％ (804/1 655) and 11.40％ (108/947),respectively.ALK gene mutations occur more common in young,adenocarcinoma patients;EGFR gene mutations occur more common in women,adenocarcinoma patients;KRAS gene mutations occur more common in elderly,male,adenocarcinoma patients.There were 6 cases of double gene mutation in 1 655 cases of ALK and EGFR detection,a total of 4 double gene mutation cases were detected in 947 cases of ALK and KRAS simultaneously.No double mutation cases were detected in 943 cases of simultaneous EGFR and KRAS mutation detection.Conclusion:The mutations of ALK,EGFR and KRAS genes in patients with non-small cell lung cancer were associated with the age,sex and histological type of patients.Mutations in the ALK fusion gene may coexist with EGFR or KRAS mutations in individual cases.