表皮生长因子受体、KRAS及BRAF基因突变与非小细胞肺癌临床病理特征的关系

Epidermal growth factor receptor, KRAS and BRAF gene mutations and their correlation with clinicopathological characteristics in non-small-cell lung cancer

目的 探讨非小细胞肺癌（NSCLC）肿瘤组织表皮生长因子受体（EGFR）、KRAS和BRAF基因突变与临床病理特征的关系.方法 采用基因测序的方法检测143例NSCLC患者肿瘤组织中EGFR基因第18、19、20、21外显子,KRAS基因第12、13密码子和BRAF基因第600密码子突变情况.采用SPSS 16.0软件分析各突变与临床病理特征的关系.结果 143例受检样本中,EGFR突变57例（39.9％）,其中第18外显子突变2例,第19外显子突变25例,第20外显子突变3例,第21外显子突变24例,多位点突变3例;KRAS突变25例（17.5％）,其中第12密码子突变23例,第13密码子突变2例;BRAF第600密码子突变2例（1.4％）.未发现EGFR、KRAS和BRAF任意两者同时突变的病例.EGFR基因突变与患者的性别、吸烟史、组织学类型、分化程度和肿瘤直径具有相关性（均P＜0.05）,与淋巴结转移及pTNM分期无相关性（均P＞ 0.05）.KRAS基因突变与患者的性别、吸烟史、组织学类型、分化程度、肿瘤直径、淋巴结转移及pTNM分期均无相关性（均P＞0.05）.结论 NSCLC患者EGFR基因突变率较高,且较常发生于女性、不吸烟、肿瘤组织较小、分化程度较患者好的腺癌组织中.KRAS基因突变率与患者性别、组织学类型等临床病理特征无关.NSCLC患者中BRAF基因突变率很低,且EGFR、KRAS和BRAF三种基因突变一般不会同时发生,为NSCLC的靶向治疗提供了客观依据。

Objective To investigate the epidermal growth factor receptor （EGFR）,KRAS and BRAF mutations and their correlation with clinicopathological characteristics in non-small-cell lung cancer （NSCLC）.Methods The mutations of exon 18,exon 19,exon 20 and exon 21 of the EGFR,codon 12,codon 13 of the KRAS and codon 600 of the BRAF gene in 143 cases of NSCLC were detected by gene sequencing.The relationship between the mutations and clinicopathological features was analyzed by SPSS 16.0.Results EGFR mutation was detected in 57 cases （39.9 %）,including 2 mutations in exon 18,25 in exon 19,3 in exon 20,24 in exon 21 and 3 multiple point mutations.KRAS mutation was found in 25 cases （17.5 %）,including 23 in codon 12 and 2 in codon 13.BRAF V600E mutation was detected only in 2 cases （1.4 %）.No patient harboring multiple EGFR,KRAS and BRAF mutations was found.EGFR mutation rate was related to gender,smoking history,histological types,differentiation and tumor size （P 〈 0.05）.However,no relationship was found among lymph node metastasis,pTNM stage and EGFR mutation （P 〉 0.05）.There was no association between KRAS mutation and clinicopathological features including gender,smoking history,histological types,differentiation,tumor size,lymph node metastasis and pTNM stage （P 〉 0.05）.Conclusions The frequency of EGFR mutation in NSCLC is high,and usually occurs in female,non-smokers,smaller tumors,better differentiation and adenocarcinomas.The frequency of KRAS mutation is not associated with the clinicolpathological features.The frequency of BRAF mutation is very low,and EGFR,KRAS and BRAF gene mutations do not occur at the same time.These results contribute to the target therapy of NSCLC.