湖北地区非小细胞肺癌EGFR基因突变及其意义的研究

Detection of Epidermal Growth Factor Receptor(EGFR)Mutations and the Significance in Patients with Non-small Cell Lung Cancer(NSCLC) of Hubei Province

目的探讨湖北地区非小细胞肺癌（NSCLC）患者中 EGFR基因的突变情况，评价湖北地区 EGFR突变的检测力度，为临床合理选择酪氨酸激酶抑制剂提供可靠的实验依据。方法采用 PCR-sanger测序法以及 ADx-ARMS法检测2010～2015年期间253例肺癌标本中 EGFR基因突变情况，探讨不同检测手段的敏感度，探讨不同性别、不同组织分型间EGFR不同外显子的突变频率差异及其临床意义。结果253例肺癌标本中共检测到突变位点93个，以 E19和 E21的突变最为常见，占比为53.76％和35.38％。ADx-ARMS法的 EGFR总突变检出率明显高于 Sanger测序法（P＝0.001）。女性肺癌患者的检出率明显高于男性（P＝0.001）。不同组织分型中，腺癌（38.01％）的检出率最高，腺鳞癌（30.77％）与大细胞癌（20％）次之，鳞癌（4.55％）较低。无吸烟史的肺癌患者检出率（51.6％，81／157）明显高于有吸烟史患者（24％，12／50）。结论与PCR-sanger测序法相比，ADx-ARMS法对临床筛选 EGFR-TKI治疗的受益亚群，预测 EGFR-TKI疗效更为敏感有意义。湖北地区女性肺癌患者中 EGFR突变频率明显高于男性，与激素水平变化及吸烟状况有关。

Objective To evaluated the prevalence of EGFR mutations in Hubei region,to provide reliable experimental basis for reasonable screening TKI beneficiaries in clinic.Methods EGFR mutation of 253 patients diagnosed with NSCLC in Hu-bei region during 2010 to 2015 was detected by PCR-sanger sequencing and ARMS assay,to investigate the sensitivity of dif-ferent methods,to explore the frequency and clinical significance of EGFR mutation in different gender,in different histologi-cal type and different exons.Results 93 of 253 NSCLC patients harbored EGFR mutation,mainly occurred in exon 19 and 21,accounting for 53.76% and 35.38% of the total EGFR mutation rate,respectively.ADx-ARMS method showed higher sensitivity （P=0.001）.The mutation detection rate of female NSCLC was significantly higher than that of male NSCLC （P=0.001）.The observed incidence of EGFR mutations in patients with adenocarcinomas （38.01%）was the highest in differ-ent histological type,followed by glandular squamous cell carcinoma （30.77%）,large cell carcinoma （20%）and squamous cell carcinoma （4.55%）.Nonsmoking patients had a higher EGFR mutation frequency （51.6%,81/157）than those with a history of smoking （24%,12/50）.Conclusion ARMS assay was more sensitive and more convenient detection method for clinical screening for EGFR-TKI treatment subpopulation.The mutation rate of female NSCLC was significantly higher than that of male NSCLC in Hubei Province.Speculated that the sexual differences in NSCLC with EGFR mutation frequencies were related to hormone levels and smoking status.