KRAS和表皮生长因子受体突变基因与原发性非小细胞肺癌的相关性

KRAS and epidermal growth factor receptor gene mutation in non-small cell lung cancer

目的 研究KRAS和表皮生长因子受体（EGFR）基因在原发性非小细胞肺癌（NSCLC）中的突变状态以及其与靶向治疗效果的相关性。方法 收集郑州大学第一附属医院收治的150例经病理证实的NSCLC患者原发肿瘤及受累的淋巴结标本，进行KRAS和EGFR突变基因序列分析。150例中12例患者纵隔淋巴结转移灶经DNA序列分析发现EGFR基因突变后给予吉非替尼进行术前辅助治疗。结果150对（分别为原发灶和受累淋巴结）标本中，2例原发肿瘤和10例淋巴结转移灶中检测到KRAS突变基因，35例原发肿瘤和44例淋巴结转移灶中检测到EGFR突变基因。KRAS和EGFR基因在原发灶和转移灶中不一致的比率分别为6.7％ （10/150）和8.7％ （13/150）。1例原发肿瘤无EGFR突变的患者接受吉非替尼治疗后效果不佳。结论 NSCLC患者原发灶和转移灶中KRAS和EGFR基因突变状态不一致，这对于应用酪氨酸激酶抑制剂靶向治疗NSCLC具有重要的参考意义。

Objective To study KRAS and epidermal growth factor receptor （EGFR） mutations in primary non-small cell lung cancer （NSCLC） and their association with the effects of targeted therapy.Methods Gene mutations of KRAS and EGFR in both primary tumors and local lymph node metastases from 150 patients with NSCLC were analyzed by direct sequencing. Twelve of the patients were given gefitinib as neoadjuvant therapy after EGFR-TKI sensitive mutations had been detected in biopsies of mediastinal lymph node metastases.Results Two primary tumors and 10 metastases were identified to have KRAS mutations, while 35 primary tumors and 44 metastases were found to have EGFR mutations.KRAS and EGFR mutation status was different between primary tumors and corresponding metastases in 6.7% （10/150） and 8.67% （13/150） patients, respectively. One patient with no TKI sensitive mutations in the primary tumor showed disease progression with gefitinib therapy. Conclusions Our results suggest that a considerable proportion of NSCLC in Chinese patients showed discrepancy in KRAS and EGFR mutation status between primary tumors and corresponding metastases. This observation may have important implications for the use of targeted TKI therapy in the treatment of NSCLC patients.