非小细胞肺癌患者ALK,EGFR及KRAS基因的检测及临床病理特征

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

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(Kirsten rat 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KR AS基因突变,采用χ2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;KR A S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KR A S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KR A S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KR AS突变共存。

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.