中国人非小细胞肺癌EGFR和K-ras基因突变与临床病理特征及厄洛替尼治疗效果的关系

目的 研究中国小细胞肺癌(NSCLC)患者表皮生长因与受体(EGFR)和K-ras基因突变情况,探讨其与NSCLC临床病理学特征及厄洛替尼治疗效果的关系.方法 利用PCR扩增和基因测序的方法检测301例中国NSCLC患者EGFR基因第18、19、20和21外显子及K-ras基因第1213密码子的突变情况,并分析其与NSCLC临床病理学特征及厄洛替尼治疗效果的关系.结果 301例患者中,99例(32.9%)有EGFR基因突变,其中第18外显子上发生突变3例,第19外显子上发生突变59例,第20外显子上发生突变2 例,第21外显子上发生突变35例.14例(4.7%)有K-ras基因突变,其中13例位于第12密码子.无同时存在EGFR和K-ras基因突变者.腺癌、无吸烟史和女性患者EGFR基因突变率较高,分别为45.7%、48.4%和49.6%.10例服用厄洛替尼有效的患者中7例携带有EGFR基因突变.结论 中国NSCLC患者EGFR基因突变率显著高于西方人群,而K-ras基因突变率则较西方人群低.联合检测EGFR和K-ras基因的突变情况可以筛选EGFR酪氨酸激酶抑制剂治疗的获益人群,并较好地预测厄洛替尼治疗晚期NSCLC的疗效.

Relationship between EGFR and K-ras mutations and clinicopathological characteristics and response to erlotinib treatment in 301 Chinese patients with non-small cell lung cancer

Objective To investigate gene mutations of epidermal growth factor receptor(EGFR)and K-ras in Chinese patients with non-small cell lung cancer (NSCLC) and its clinicopathological significance, and to analyze the correlation between these mutations and tumor response to erlotinib treatment. Methods Mutations of exons l8, 19, 20and21 of the EGFR and codons 12, 13 of the K-ras in 301 cases of NSCLC were detected by PCR-amplification and gene sequencing The relationship between the mutations and clinicopathological characteristics of the 301 patients was analyzed. Results EGFR mutations were present ih 32.9% (99/301) of the samples: 3 mutation in exon 18 , 59 in exon 19, 2 in exon 20, and 35 in exon 21. Mutations of K-ras were present in 4.7% (14/301) of the samples : 13 in codon 12 and 1 in codon 13. EGFR mutations were never found in tumors with K-ras mutations, suggesting a mutually exclusive relationship. EGFR mutations were more common in adenocarcinomas, non-smokers ahd fcemales. Seven out of 10 erlotinib-treated patients with disease control carried EGFR mutation. Conclusion The frequency of EGFR mutation in Chinese NSCLC patients is higher than that in Westerners , but the frequency of K-ras mutation is quite opposite. Combined detection of EGFR gene and K-rais gene mutation may help clinicians to choose patients who may gain benefit from EGFR tyrosme kinase inhibitor (EGFR-TKI) treatment, and to predict their response to erlotinib treatment and prognosis.