PTEN基因缺失与EGFR突变型非小细胞肺癌患者EGFR-酪氨酸激酶抑制剂疗效的关系

Analysis of epidermal growth factor receptor gene copy status in non-small cell lung cancer by fluorescence in situ hybridization

目的 探讨PTEN基因缺失与EGFR突变型非小细胞肺癌患者EGFR酪氨酸激酶抑制剂的疗效关系。方法收集169例使用EGFR-TKI的EGFR基因突变型非小细胞肺癌,采用LSI PTEN/CEP10探针对组织标本进行PTEN基因拷贝数的检测,并分析PTEN基因缺失与患者临床病理学及EGFR-TKI的疗效关系。结果在169例NSCLC病例中5例（3.0%）PTEN基因杂合性缺失,杂合性缺失组与非缺失组ORR（0.0%对42.5%）及DCR（60.0%对92.5%）无显著差异（P分别0.078及0.058）。PTEN基因缺失组PFS及OS分别为4.9月及13.2月,显著低于非缺失组PFS 12.1月（HR=3.64,95%CI=1.57~9.00,P=0.002）及28.1月（HR=2.86,95%CI=1.04~7.89,P=0.034）。结论 PTEN基因缺失可能作为EGFR突变型非小细胞肺癌患者EGFR-TKI原发性耐药的有效指标。

Objective To explore the relationship between PTEN loss and responsiveness and outcome of EGFR-TKIs in EGFR-mutated NSCLC patients. Methods A total of 169 patients with advanced NSCLC with full clinical and following data treated with EGFR-TKIs were included. PTEN copy number was analyzed using fluorescent in situ hybridization （FISH）. Results A total of 5 patients （3.0%） PTEN copy number loss were identified among 169 patients with TKI-sensitive EGFR mutations. PTEN loss had no association with gender （P=0.483）, histological subtype （P=0.375） and smoking status （P=0.339）. PTEN loss had no correlation with ORR （0.0% vs. 42.5%） and DCR（60.0% vs. 92.5%） compared with those of intact PTEN （P=0.078 and 0.058, respectively）. However, PTEN loss was correlated with shorter PFS （4.9 months vs. 13.2 months, HR=3.64, 95%CI= 1.57N9.00, P=0.002） and shorter OS （12.1 months vs. 28.1 months; HR=2.86, 95%CI=1.04-7.89, P =0.034）compared to the group with intact PTEN. Conclusion PTEN loss may be the indicator of de novo resistance and poor outcome in patients with NSCLC treated with EGFR-TKIs.