赣南地区非小细胞肺癌EGFR突变和ALK重排的临床研究

Clinical research on EGFR mutation and ALK rearrangement in non-small cell lung cancer in Gannan region

目的:探讨赣南地区原发性非小细胞肺癌患者表皮生长因子受体(Epidermal growth factor receptor,EGFR)突变和间变型淋巴瘤激酶(Anaplastic lymphoma kinase,ALK)重排的基因分型和临床病理特征,科学指导此类患者优选靶向用药。方法:入组332例原发性非小细胞肺癌病例,采用ARMS-PNA技术检测EGFR基因第18、19、20、21外显子突变和应用不平衡法检测其中297例的ALK重排,回顾性分析EGFR突变和ALK重排患者的临床病理特征。结果:EGFR突变146例,阳性率为43.98%(146/332),其中19del突变77例,L858R突变54例,二者占89.73%。单因素分析发现,女性、不吸烟、T_(1)~T_(2)期肺腺癌患者EGFR突变率高于男性、吸烟、T_(3)~T_(4)期非腺癌患者(P均=0.000);Logistic回归分析表明,女性、腺癌及T_(1)~T_(2)期是发生EGFR突变的风险因素。ALK重排表达23例,阳性率为7.74%(23/297)。单因素分析结果显示,新鲜组织和女性、不吸烟且合并淋巴结转移(N_(1-3))的Ⅲ~Ⅳ期患者ALK重排的表达率高于石蜡组织和男性、吸烟且无淋巴结转移(N_(0))的Ⅰ~Ⅱ期患者(P均<0.05);Logistic回归分析表明,性别、年龄、吸烟史、组织样本、病理类型、临床分期及N、M分期等均不是发生ALK重排的风险因素。此外,EGFR和ALK基因共存突变6例,占2.02%(6/297)。结论:赣南地区原发性非小细胞肺癌患者EGFR突变和ALK重排阳性率相对较高,EGFR突变好发于T<5 cm、女性、腺癌患者,亚型以19del突变相对多见;ALK重排可能是NSCLC中相对独立的致癌因子。

Objective:To explore the genotyping and clinicopathological features of epidermal growth factor receptor(EGFR)mutation and anaplastic lymphoma kinase(ALK)rearrangement in patients with non-small cell lung cancer(NSCLC)in Gannan region,thus scientifically guide such patients to choose targeted drugs.Methods:A total of 332cases of primary NSCLC were enrolled.The mutations of exon 18,19,20 and 21 of EGFR gene were detected by amplification refractory mutation system-peptide nucleic acid(ARMS-PNA)technique and the expression of ALK rearrangement was screened by the 5′/3′imbalance strategy for reverse transcription followed by quantitative polymerase chain reaction(RT-qPCR)analysis among 297 cases of them.The clinicopathological features of patients with EGFR mutation or ALK rearrangement were retrospectively analyzed.Results:There were 146 cases of EGFR mutation,hence a positive rate of43.98%(146/332).Among 146 EGFR-mutant cases,77 were 19del mutation,whereas 54 were L858R mutation,the two accounting for 89.7%.The univariate analysis showed that the EGFR mutation rate in women,non-smoking,and lung adenocarcinoma patients with T_(1)-T_(2)stage were significantly higher than that in men,smoking,and non-lung adenocarcinoma patients with T_(3)-T_(4)stage(all P=0.000).The logistic regression analysis revealed that women,adenocarcinoma,and T_(1)-T_(2) stages were the risk factors for EGFR mutation.There were 23 cases of ALK rearrangement,hence the expression rate of 7.74%(23/297).The univariate analysis found that the expression rate of ALK rearrangement were significantly higher in fresh tissue and female,non-smoking patients with N_(1-3) stage combined with stageⅢ-Ⅳthan in paraffin tissue and male,smoking patients with stage N_(0) combined withⅠ-Ⅱstage(all P<0.05).Surprisingly,the following logistic regression analysis indicated that gender,age,smoking history,tissue samples,pathological type,clinical stage and N,M stages were all not risk factors for ALK rearrangement.In addition,there were 6 cases with coexisting mutations of EGFR and ALK genes,accounting for 2.02%(6/297).Conclusion:The positive rate of EGFR mutation and ALK rearrangement in patients with primary NSCLC in Gannan region was relatively higher,EGFR mutation is common in patients with T<5 cm,female and adenocarcinoma,and 19del mutation is the most common subtype;ALK rearrangement may be a relatively independent carcinogen in NSCLC.