肺腺癌患者表皮生长因子受体基因突变情况及与Ki-67和甲状腺转录因子-1阳性表达的关系

Epidermal growth factor receptor mutation and its relationship with the positive expression of Ki-67 and thyroid transcription factor-1 in lung adenocarcinoma

目的探讨肺腺癌组织表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变情况及与Ki-67及甲状腺转录因子-1(thyroid transcription factor-1,TTF-1)阳性表达的关系。方法取172例肺腺癌患者手术切除及活检组织标本,采用测序法检测EGFR基因突变情况,免疫组织化学法检测肺腺癌组织Ki-67及TTF-1蛋白阳性表达,比较不同临床病理特征及Ki-67、TTF-1蛋白阳性与阴性表达者EGFR基因突变率。结果 172例中EGFR基因突变66例(38.4%),突变位点主要位于第19外显子37例(56.1%)、20外显子4例(6.0%)及21外显子17例(25.8%),Ki-67蛋白、TTF-1蛋白阳性表达率分别为77.33%和80.23%;腺泡型、乳头型及贴壁型肺腺癌患者EGFR基因突变率(54.6%、75.0%、52.4%)高于实体型及微乳头型患者(10.2%、19.1%)(P<0.05);EGFR基因突变率在年龄≤60岁(56.2%)、女性(50.7%)、病理分级高分化及中分化(51.2%、40.4%)、TTF-1蛋白表达阳性者(45.7%)高于年龄>60岁(25.3%)、男性(30.1%)、病理分级低分化(17.6%)、TTF-1蛋白阴性表达者(8.8%)(P<0.05);Ki-67蛋白阳性、阴性者EGFR基因突变率(36.8%、43.6%)比较差异无统计学意义(P>0.05);男性未吸烟及轻度吸烟者EGFR基因突变率(54.5%、66.7%)高于重度吸烟者(22.3%)(P<0.05),女性未吸烟者EGFR基因突变率(51.6%)高于吸烟者(28.6%)(P<0.05)。结论肺腺癌患者EGFR基因突变主要位于19~21外显子,其突变与患者年龄、性别、吸烟及TTF-1蛋白阳性表达有关。

Objective To investigate the mutation of epidermal growth factor receptor （EGFR） in lung adenocarcinoma and its relationship with the positive expressions of Ki-67 and thyroid transcription factor-1 （TTF-1）. Methods Totally 172 patients with lung adenocarcinoma specimens were detected the EGFR mutation by direct sequencing method. The expressions of Ki-67 and TTF-1 protein were detected by immunohistochemistry. The clinicopathological features and the mutation rates of EGFR in patients with positive and negative Ki-67 and TTF-1 were compared. Results Of these 172 patients with lung adenocarcinoma, EGFR gene mutation was found in 66 patients （38.4%）, with exon 19 in 37 patients （56. 1%）, exon 20 in 4 （6.0%） and exon 21 in 17 （25.8%）. The positive rates of Ki-67 and TTF-1 proteins were 77.33% and 80.23%//00. The EGFR mutation rate was significantly higher in patients with acinar type （54.6~/oo）, papillary type （75.0%） and lepidic type （52.4%） than that in solid type （10.2%） and micropapillary type （19.1%） （P〈0.05）. The EGFR mutation rate was significantly higher in patients 〈60 years old （56. 2%）, females （50. 7%）, highly or moderate differentiated patients （51.2 %, 40.4 % ）, and positive TTF-I protein patients （45.7 % ） than that in patients 60 years old （25. 3%）, males （30. 1%）, low differentiated patients （17. 6%） and negative TTF-1 protein patients （8.8%） （P〈0.05）. There was no significant difference in the mutation rate of EGFR between the patients with positive and negative Ki-67 protein （36.8% vs 43.6%） （P〈0.05）. The mutation rate of EGFR gene was significantly higher in non-smoking （54.5%） and light smoking males （66.7%） than that in heavy smoking males （22.3%） （P〈0.05）, and in non-smoking females （51.6 %） than that in smoking females （28.6 %） （P〈0.05）. Conclusion EGFR gene mutation in patients with lung adenocarcinoma is mainly located in exon 19 to 21, and is correlated with the age,gender, smoking and positive expression of TTF-1 protein.