临床病理特征及甲状腺转录因子1表达对非小细胞肺癌表皮生长因子受体突变的预测价值

Predictive values of clinicopathological features and expression of thyroid transcription factor 1 for epidermal growth factor receptor mutations in non-small cell lung cancer

目的 探讨非小细胞肺癌（NSCLC）患者的临床病理特征及甲状腺转录因子1（TTF-1）表达对表皮生长因子受体（EGFR）突变的预测价值.方法 采用突变扩增阻滞系统（ARMS）法和免疫组织化学法对山西省肿瘤医院2013年1月至2014年12月经病理诊断的283例NSCLC标本进行EGFR（18、19、20、21外显子）基因突变和TTF-1蛋白表达检测,并分析患者临床病理特征、TTF-1表达与EGFR基因突变的关系,探讨二者在预测EGFR突变中的价值.结果 283例NSCLC中,EGFR基因突变率为30.0％（85/283）,其中3例存在双突变,分别为18、20外显子双突变1例,19、21外显子双突变1例,20、21外显子双突变1例.EGFR基因突变与患者性别、组织学类型、是否有吸烟史、TTF-1表达有关（均P〈0.001）,但与年龄和肿瘤位置无关（P=0.785,P=0.138）.将突变率高的影响因素（女性、腺癌、无吸烟史、TTF-1阳性）联合可使EGFR突变的阳性预测值达到57.6％,将突变率低的影响因素（男性、非腺癌、有吸烟史、TTF-1阴性）联合可使EGFR突变的阴性预测值达到90.3％.结论 NSCLC患者临床病理特征及TTF-1表达情况对EGFR突变具有较好的预测价值,可为临床治疗决策的制订提供参考.

Objective To study the values of clinicopathological features and expression of thyroid transcription factor 1 （TTF-1） in predicting the mutation status of epidermal growth factor receptor （EGFR） gene in patients with non-small cell lung cancer （NSCLC）. Methods Mutation status of exons 18, 19, 20 and 21 in EGFR, and expression of TTF-1 protein in 283 cases of NSCLC diagnosed in Shanxi Provincial Cancer Hospital from January 2013 to December 2014 were analyzed by using amplification refractory mutation system （ARMS） and immunohistochemical method. The correlation of EGFR mutations with the clinicopathological features and TTF-1 expression were studied to explore the values of them in the prediction of EGFR mutations. Results Among 283 cases of NSCLC, the rate of EGFR gene mutation was 30.0 %（85/283）, including 3 cases with double mutations（exon 18 and exon 20 double mutations in one case, exon 19 and exon 21 double mutations in one case, exon 20 and exon 21 double mutations in one case）. The EGFR gene mutations were associated with gender, histological type, history of smoking, and expression of TTF-1 （all P〈0.001）, but not related to age and tumor location （P= 0.785, P= 0.138）. The combination of factors with high mutation rates （women, adenocarcinoma, no smoking, and TTF-1 positive） made the positive predictive value of EGFR mutations up to 57.6 %. And the combination of factors with low mutation rates （male, nonadenocarcinoma, smoking history, TTF-1 negative） made the EGFR negative predictive value up to 90.3%. Conclusion The combination of clinicopathological features and TTF-1 expression status in patients with NSCLC has a great predictive value for EGFR mutations, which can provide a useful reference for clinical treatment decision-making.