非小细胞肺癌表皮生长因子受体基因突变及其临床背景关系分析

Epidermal growth factor receptor mutations in non-small cell lung cancer and clinical background

目的探讨非小细胞肺癌患者EGFR基因突变状况以及与各临床背景间的关系。方法采用扩增阻遏突变系统taqman-ARMS法对257例非小细胞肺癌患者肿瘤组织进行了EGFR基因检测,并回顾性分析突变情况与病理类型、TNM分期、患者性别、年龄及生活习惯等临床背景间的关联性。结果 257例非小细胞肺癌样本中,EGFR突变率为38.5%,93例存在单一突变,6例存在两种突变,突变主要集中在19外显子缺失突变和21外显子的点突变。腺癌突变率明显高于鳞癌及其他非腺癌(P<0.01)。女性突变率高于男性(P<0.01)。≤65岁与>65岁两组间差异无统计学意义(P>0.05)。非吸烟者突变率明显高于吸烟者(P<0.01),突变与吸烟年限关联不明显,与日吸烟量明显相关(P<0.01)。根据TNM分期,Ⅰ、Ⅱ、Ⅲ、Ⅳ期各组间比较突变率差异无统计学意义。中、高分化间突变与低分化相比较差异有统计学意义(均P<0.01)。结论非小细胞肺癌EGFR基因突变与性别、组织学分型、肿瘤分化程度、吸烟以及日吸烟量等临床特征显著相关,与年龄、淋巴结转移、TNM分期及吸烟年限等无明显相关。

Objective To investigate the relationship between epidermal growth factor receptor(EGFR)mutations and different clinical backgrounds in patients with non-small cell lung cancer(NSCLC).Methods EGFR mutations in the tumor tissues of 257 NSCLC patients were analyzed by TaqMan-ARMS(TaqMan-amplification refractory mutation system).The mutation of EGFR was explored in correlation with the clinicopathological features,TNM stage,gender,age and habits of patients.Results 99(38.5%)EGFR mutations,which were mainly located in exon 19 with the pattern of deletion mutation and exon 21 with the point mutation,were identified among 257 NSCLC patients.The mutation rate was higher in patients with adenocarcinoma and adenosquamous carcinoma than that in patients with squamous cell carcinomas and other subtypes(all P <0.01).Mutation rate in female was higher than that in male(P <0.01).However,no evident association was found between EGFR mutation and age(P >0.05).EGFR gene mutations occurred more frequently in non-smokers compared with smokers(P <0.01).EGFR mutation was not associated with smoking years,but significantly correlated with daily smoking(P <0.01).There was no significant difference between EGFR gene mutation and clinical TNM stage of NSCLC(Ⅰ,Ⅱ,Ⅲ and Ⅳ).EGFR mutation rates in patients with different pathological characteristics,to some extent,were different.Mutation was significantly different between low differentiation and middle or high differentiation(P <0.01).Conclusion EGFR gene mutation in NSCLC was significantly correlated with gender,histological type,tumor differentiation,smoking and daily smoking amount but not with age,lymph node metastasis,TNM stages and smoking years.