Background: Epidermal growth factor receptor (EGFR) and KRAS gene are important driver genes of non-small cell lung cancer (NSCLC). The studies are mainly focused on detection of EGFR gene for advanced NSCLC, and the mutation feature of EGFR and KRAS gene in early NSCLC tissue is unknown. This study aims to investigate the mutations of EGFR and KRAS gene in NSCLC, and the relationship between the genotype and clinicopathologic features.
Methods: The hotspot mutations in EGFR and KRAS gene in 754 tissue samples of stage I-IIIa NSCLC from Department of Pathology, Peking Union Medical College Hospital were detected by modified amplification refractory mutation system (ARMS) real-time PCR kit, and analyzed their correlation with clinical variables.
Results: The hotspot mutation rates in EGFR and KRAS were 34.5% and 13.1% respectively, and there were EGFR-KRAS double mutations in 3 samples. The mutation rate of EGFR was higher in females than that in males (39.5% vs 29.4%, P=0.076), significantly increased in adenocarcinomas (38.7%) compared to that in the other forms of NSCLC (P<0.01), but still lower than that reported in some Asian studies of advanced adenocarcinoma (-50%). Meanwhile, the mutation rate of KRAS was remarkably higher in males than that in females (16.6% vs 9%, P=0.048), increased in adenocarcinomas compared to that in the other forms of NSCLC, but the difference was not significant (P=0.268). Samples harbored EGFR mutation were younger than those harbored KRAS mutation (P=0.031,5), and had significant difference in gender between the two groups (P<0.01).
Conclusions: The mutation rate of EGFR in stag I-IIIa NSCLC patients was lower than that in advanced NSCLC patients. And the percentage of the NSCLC patients with EGFR-KRAS double mutations is 0.9%.
背景与目的 表皮生长因子受体（epidermal growth factor receptor, EGFR）和KRAS基因是非小细胞肺癌（non-small cell lung cancer, NSCLC）重要的分子靶点，但目前研究主要集中在晚期NSCLC组织和血浆标本的EGFR检测，早期NSCLC组织样本中EGFR和KRAS突变特征尚不清楚。本研究将探讨I期-IIIa期NSCLC EGFR和KRAS基因突变与相关临床病理特征的关系。方法 采用突变扩增系统（amplification refractory mutation system, ARMS）PCR方法检测北京协和医院病理科提供的754例I期-IIIa期NSCLC组织样本的EGFR和KRAS基因突变状况，分析基因突变率及其与临床病理特征的关系。结果 EGFR和KRAS基因热点突变的突变率分别为34.5%和13.1%，其中有3例样本具有EGFR和KRAS基因的双突变。EGFR基因在女性中的突变率高于男性（39.5% vs 29.4%, P=0.076），在腺癌中的突变率（38.7%）高于鳞癌、腺鳞癌、大细胞癌（P<0.01），但仍明显低于其他研究报道的亚裔晚期腺癌突变率（-50%）。KRAS基因突变在男性中的突变率高于女性（16.6% vs 9%, P=0.048），且在腺癌中的突变率也高于其他类型，但差异不显著（P=0.268）。与KRAS基因突变阳性组相比，EGFR基因突变阳性组在年龄分布上有年轻化的趋势（P=0.031,5），在性别分布上有显著性差异（P<0.01）。结论 I期-IIIa期NSCLC EGFR基因突变率较晚期患者低，且EGFR和KRAS基因双突变的发生率为0.9%。.