探讨ⅢA-N2期NSCLC原发瘤体与N2淋巴结及外周血中EGFR基因突变的差异性

Epidermal growth factor receptor mutations in primary tumors, N2 lymph nodes, and plasma samples in Chinese patients with stage ⅢA-N2 non-small cell lung cancer

目的:探讨ⅢA-N2期非小细胞肺癌(non-small cell lung cancer,NSCLC)原发瘤体、N2淋巴结及外周血中表皮生长因子受体基因(epidermal growth factor receptor,EGFR)突变状况是否存在差异性,从基因层面为目前所提倡的"个体化医疗"提供一些有价值的参考指标。方法:用突变富集—液相芯片法检测中山大学肿瘤防治中心及延安大学附属医院2014年11月至2015年11月间手术切除并经病理证实49例病理分期为ⅢA-N2期的NSCLC原发瘤体、N2淋巴结及外周血中EGFR基因19号及21号外显子突变状况,并对检测结果整理分析。结果:49例患者中,有18例(36.7%)从原发瘤体中检测出EGFR基因突变,11例(22.4%)从N2淋巴结中检测出EGFR基因突变,而从外周血中仅有2例(4.1%)检测出EGFR基因突变;其中9例仅有原发瘤体中EGFR基因突变,2例仅有N2淋巴结中EGFR基因突变;而外周血中检测出EGFR基因突变的2例,同时也在原发瘤体及N2淋巴结中检测出EGFR基因突变。结论:在NSCLC原发瘤体及转移淋巴结中EGFR基因突变状况存在一定的差异性;在ⅢA-N2期NSCLC患者外周血中,EGFR基因突变检出率较低。以上结果提示肿瘤在转移过程中从分子水平上可能已经发生改变,存在一定的差异性,为今后EGFR-TKIs治疗NSCLC乃至于其他针对基因靶点的个体化治疗提供有价值的思考。

Objective： Mutations in epidermal growth factor receptor（EGFR） can predict tumor response to tyrosine kinase inhibitors（TKIs） in non-small cell lung cancer（NSCLC）. However, not all cases of NSCLC with EGFR mutations can respond well; thus, discovering the heterogeneity of NSCLC at the molecular level is necessary. This study aimed to determine the discrepancy in EGFR mutations in primary tumors, N2 lymph nodes, and plasma samples. Methods： Primary tumors, N2 lymph nodes, and plasma samples obtained from 49 patients with stage ⅢA-N2 NSCLC were analyzed for EGFR mutations in exons 19 and 21 by using mutant-enriched liquidchip technology. Results： In 49 patients, we detected 18（36.7%） EGFR mutations in primary tumors, 11（22.4%） mutations in N2 lymph nodes, and 2（4.1%） mutations in plasma samples. Eleven（22.4%） cases showed discordance in EGFR mutations between primary tumors and N2 lymph nodes. In nine cases, EGFR mutations were detected only in primary tumors, whereas EGFR mutations were detected only in N2 lymph nodes in two cases. In addition, EGFR mutations were detected in the plasma samples of two patients, who also carry mutations in their primary tumors. Conclusion： A considerable proportion of NSCLC cases showed discrepancy in EGFR mutations between primary tumors and N2 lymph nodes. In addition, the detection rate of EGFR mutations was lower in plasma samples obtained from patients with stage IIIA-N2 NSCLC. All of the results indicated tumor heterogeneity at the molecular level during metastasis, and this heterogeneity may have implications during treatment with TKIs.