肺腺癌组织TTF-1和EGFR表达及与EGFR第19、21号外显子突变的关系

Correlation between TTF-1 expression and EGFR expression and EGFR mutations of 19 and 21 exons in lung adenocarcinoma

目的探讨肺腺癌组织中甲状腺转录因子-1(TTF-1)和表皮生长因子受体(EGFR)表达及两者与EGFR第19、21号外显子突变间的关系。方法收集153例手术及穿刺活检肺腺癌标本并采用免疫组化法检测TTF-1和EGFR蛋白表达;采用扩增阻滞突变系统(ARMS)法检测EGFR基因第19和21号外显子突变,并分析TTF-1、EGFR表达和EGFR突变三者间的关系。结果 153例肺腺癌组织中,EGFR突变68例,其中32例为第19号外显子,36例为21号外显子;TTF-1表达(0^+)、(++)、(+++)分别为48例、40例、65例,其对应标本的EGFR(+++)表达率依次为50.0%(24/48)、62.5%(25/40)和83.1(54/65),EGFR突变率依次为25.0%(12/48)、37.5%(15/40)和63.1%(41/65);EGFR表达(0^+)、(++)、(+++)分别为18、32、103例,其对应标本的EGFR突变率分别为16.7%(3/18)、34.4%(11/32)和52.4%(54/103)。随TTF-1表达增强,EGFR表达和EGFR突变率亦相应增加,呈正相关(r=0.940,0.916;P均<0.05),差异有统计学意义(P<0.05);随EGFR表达增加,EGFR突变率亦相应增加,呈相关性(r=1.000),差异有统计学意义(P<0.05)。结论肺腺癌中TTF-1、EGFR表达与EGFR第19和21号外显子突变三者间存在相关性,检测TTF-1表达可以用于肺腺癌靶向治疗的预筛,在急需要化疗/靶向治疗而EGFR突变检测难以实施的地区,可通过联合检测TTF-1、EGFR蛋白来预测EGFR基因突变情况,以指导及时有效的临床诊断和治疗。

Objective To investigate the relationship between expressions of thyroid transcription factor 1（TTF-1） and epidermal growth factor receptor（ EGFR）,and EGFR mutations of 19 and 21 exons in lung adenocarcinomas. Methods For 153 cases of lung adenocarcinomas obtained by surgical resection and puncture biopsy,immunohistochemistry was used to detect the expression of TTF-1 and EGFR,and amplification refractory mutation system was used to detect mutations of EGFR 19 and 2l exons. Furthermore,the relationship between expressions of TTF-1 and EGFR,and EGFR mutations of 19 and 21 exons were also investigated. Results Sixty-eight cases of EGFR gene mutations were found,including 32 cases in 19 exons and 36 cases in 21 exons. Among 153 cases of lung adenocarcinomas,50. 0%（24 /48）,62. 5%（25 /40） and 83. 1（54 /65） of EGFR expression（ ＋ ＋ ＋） and 25. 0%（12 /48）,37. 5（15 /40）,63. 08%（41 /65） of EGFR mutations were found in 48,40 and 65 cases of TTF-1 expression（0-＋） 、（ ＋ ＋） and（ ＋＋ ＋）,respectively. Besides,16. 7%（3 /18）,34. 4%（ 11 /32） and 52. 4%（ 54 /103） of EGFR mutations were found in 18,32,103 cases of EGFR expression of（0-＋）,（ ＋ ＋）,（ ＋ ＋ ＋）. It was observed that the ratios of EGFR expression（ ＋ ＋ ＋） and EGFR mutations also increased with the increased expression of TTF-1. It was also found that the EGFR mutations increased correspondingly with the increased EGFR expression. The correlations of TTF-1 expression and EGFR expression,TTF-1 expression and EGFR mutations,EGFR expression and EGFR mutations were statistically significant with the corresponding r of 0. 940,0. 916,and 1. 000,respectively. Conclusion Expressions of TTF-1 and EGFR and EGFR mutations of 19 and 21 exons are relevant to each other in lung adenocarcinomas. Detection of TTF-1 expression can be used to preselect the EGFR mutations for target therapy. Clinical doctors can predict EGFR mutations to guide the timely and effective clinical diagnosis and treatment by combined evaluating the expression of TTF-1 and EGFR when it is urgent for chemotherapy or target therapy but hard to undertake the detection of EGFR gene mutation in some areas.