肺腺癌EGFR、KRAS基因突变、ALK融合蛋白状态分析

Investigation of EGFR、KRAS Mutations and ALK Protein Fusion Status in Lung Adenocarcinoma Patients

目的分析肺腺癌中EGFR、KRAS、ALK三种肿瘤驱动基因的突变状态及与其临床病理特征、肿瘤分期的关系。方法 85例肺腺癌EGFR,KRAS基因突变采用ARMS法检测,ALK融合蛋白用特异性抗ALK单克隆抗体(克隆号:D5F3)采取免疫组织化学法检测。结果 EGFR,KRAS,和ALK融合蛋白检测阳性率分别是62%,15%,和14%。EGFR基因突变更常见于女性。KRAS基因突变更常见于男性及有吸烟史患者。ALK融合蛋白更常见于年轻及肿瘤分期Ⅲ/Ⅳ患者。检测中发现了8例双突变病例。结论结果进一步证实了EGFR、KRAS基因突变与ALK融合蛋白并非完全互斥。对于肺腺癌患者进行全面的基因检测非常重要,在选择靶向治疗时更应考虑到多种变异同时存在的情况。

Objective To evaluate the mutations of EGFR,KRAS,ALK fusion protein and their relations with clinical pathological features and stages of lung adenocarcinoma. Methods In a cohort of patients with lung adenocarcinoma（ n = 85）,EGFR,KRAS mutations were detected by amplification refractory mutation system in multiple quantitative polymerase chain reaction（ ARMSmultiq PCR）. ALK fusion protein was screened using immunohistochemistry（ IHC） conducted with an anti-ALK monoclonal antibody（ clone D5F3,Ventana）. Results The mutation rate was 62%,15%,14% for EGFR,KRAS,ALK fusion protein in 85 lung adenocarcinoma cases,respectively. EGFR mutations were more frequently observed in female patients. KRAS mutations were more frequently detected in male patients,and smokers. ALK fusion protein was more frequently observed in younger patients,and 3/4 patients. 8 cases of co-mutationswere detected. Conclusion We have further confirmed that EGFR,KRAS mutations and ALK fusions are not mutually exclusive through the analysis of 85 lung adenocarcinoma cases. It is vital for a complete molecular analysis to be performed on all lung adenocarcinoma patients,and the possibility of multiple mutations must be taken into account when choosing targeted therapy.