肺腺癌中TTF-1和Napsin A表达与EGFR突变的相关性

发布时间：2018-05-24 07:00

本文选题：肺腺癌 + TTF-1　；参考：《皖南医学院》2017年硕士论文

【摘要】：目的:目前,关于肺腺癌患者分子靶向治疗获益的关键是治疗前行EGFR基因检测,了解基因突变状况,但该过程繁琐、费用高及假阴性等使部分患者失去了检测时机,延误治疗。因此,有必要探寻新的与EGFR基因突变有关的标志物预测其突变来指导临床治疗。甲状腺转录因子-1(TTF-1)与天门冬氨酸蛋白酶A(Napsin A)作为肺腺癌患者的诊断标志物,一般采用免疫组化法测定,此方法比EGFR基因突变检测更为简便、快速。据此,本项实验采用免疫组化法检测肺腺癌中TTF-1与Napsin A的表达和ARMS法检测EGFR突变,探讨肺腺癌组织中二者的表达情况与EGFR突变状态的相关性及临床预测价值。方法:收集2014年03月至2016年06月在皖南医学院弋矶山医院病理科经组织学确诊的原发性肺腺癌患者160例,入选的所有患者均行EGFR突变检测,并有完整的检测结果。所有病例取材前均未接受放疗和化疗,并且能获得较为完整的临床资料。所有相关资料均从患者既往住院病历库中调阅,包括年龄、性别、吸烟史、组织分化程度、TNM分期。所有标本均经10%中性缓冲甲醛固定,石蜡包埋,HE染色后在光镜下观察形态学改变,应用免疫组化法检测TTF-1和Napsin A的表达情况,应用ARMS法检测患者EGFR的突变状况。采用SPSS18.0软件分析系统,计数资料用χ2检验,P0.05为差异有统计学意义。结果:1.入组肺腺癌患者中EGFR突变率为55%,主要发生在19和21外显子,19外显子占52.3%,21外显子占43.1%。女性(P=0.001)、不吸烟(P=0.026)、组织分化程度较高(P=0.021)的患者具有更高的EGFR突变;2.TTF-1和Napsin A在肺腺癌中的阳性表达率分别为88.1%和86.3%,两者双阳性表达率为83.1%,且二者的表达与年龄、TNM分期没有相关性(P0.05),而与性别(P=0.012、P=0.035)、吸烟(P=0.018、P=0.036)、组织分化程度(P=0.013、P=0.009)密切相关。二者具有很好的正相关性(Kappa系数=0.637,r=0.639,P=0.000),TTF-1和Napsin A在女性、不吸烟、组织分化程度较高的肺腺癌患者中表达率较高;3.TTF-1和Napsin A表达与EGFR突变明显正相关(r=0.367、P=0.000,r=0.405、P=0.000),TTF-1阳性与阴性表达中EGFR突变率分别为61.7%、5.3%,差异具有统计学意义(P=0.000),TTF-1预测EGFR突变的灵敏度为98.9%,特异度为25%,阳性预测价值为61.7%,阴性预测价值为94.7%;Napsin A阳性与阴性表达中EGFR突变率分别为63%、4.5%,差异具有统计学意义(P=0.000),Napsin A预测EGFR突变的灵敏度为98.9%,特异度为29.2%,阳性预测价值为63.0%,阴性预测价值为95.5%;两者双阳性表达的EGFR突变率为65.4%,二者联合预测EGFR突变的灵敏度为98.9%,特异度为36.1%,阳性预测价值为65.4%,阴性预测价值为96.3%。结论:1.在肺腺癌中EGFR突变状态较高,多见于19、21外显子,女性、不吸烟、组织分化较高可以预测肺腺癌患者的高EGFR突变率;2.TTF-1和Napsin A在肺腺癌组织中的表达水平较高,二者显著相关,可作为肺腺癌诊断的参考指标,特别是在女性、不吸烟、组织分化程度较高的肺腺癌患者中表达明显;3.肺腺癌组织中TTF-1和Napsin A表达与EGFR突变具有很好的相关性,二者的表达水平可以预测EGFR突变状态,且TTF-1与Napsin A联合表达具有更高的EGFR突变可能,为临床肺腺癌患者靶向治疗提供参考价值。
[Abstract]:Objective: at present, the key to the molecular targeting therapy of lung adenocarcinoma is to treat the EGFR gene and understand the mutation of the gene, but the process is tedious, the high cost and the false negative cause some patients to lose the time of detection and delay the treatment. Therefore, it is necessary to explore new markers related to the mutation of EGFR gene to predict their mutation To guide clinical treatment, thyroid transcription factor -1 (TTF-1) and aspartic proteinase A (Napsin A) are used as diagnostic markers for lung adenocarcinoma, and are generally determined by immunohistochemical method. This method is more convenient and rapid than EGFR gene mutation detection. Accordingly, this experiment uses immunohistochemical method to detect TTF-1 and Napsin A in lung adenocarcinoma. The correlation of the expression of two in the lung adenocarcinoma tissue and the mutation status of EGFR in the lung adenocarcinoma tissue and the clinical predictive value were examined by ARMS method. Methods: 160 cases of primary lung adenocarcinoma confirmed by histology of the pathology department of Yi La hospital from 03 months to 06 months of 2016 were collected from 03 months to 06 months of 2014. All the patients were selected for EGFR mutation. All cases were not treated with radiotherapy and chemotherapy before all cases were taken, and more complete clinical data were obtained. All the related data were read from the patient's Hospital history library, including age, sex, smoking history, degree of tissue differentiation, TNM staging. All specimens were fixed by 10% neutral buffered formaldehyde and paraffin wax. After HE staining, the morphological changes were observed under the light microscope. The expression of TTF-1 and Napsin A was detected by immunohistochemistry. The mutation of EGFR was detected by ARMS. The SPSS18.0 software was used to analyze the system. The count data was tested by chi 2, and P0.05 was statistically significant. The result: the EGFR mutation rate in the 1. patients with lung adenocarcinoma was 55%. Mainly in exons 19 and 21, 19 exons 52.3%, 21 exons in 43.1%. women (P=0.001), non smoking (P=0.026), and higher tissue differentiation (P=0.021) patients with higher EGFR mutations; the positive expression rate of 2.TTF-1 and Napsin A in lung adenocarcinoma was 88.1% and 86.3%, both positive expression rates were 83.1%, and the two person's table TNM staging was not associated with age (P0.05), but was closely related to sex (P=0.012, P=0.035), smoking (P=0.018, P=0.036), and the degree of tissue differentiation (P=0.013, P=0.009). The two had a good positive correlation (Kappa coefficient =0.637, r=0.639, P=0.000). The expression of 3.TTF-1 and Napsin A was positively correlated with EGFR mutation (r=0.367, P=0.000, r=0.405, P=0.000). The EGFR mutation rate of TTF-1 positive and negative expression was 61.7%, 5.3%, respectively, and the difference was statistically significant (P=0.000). The sensitivity of the TTF-1 prediction mutation was 98.9%, the specificity was 25%, the positive predictive value was 61.7%, negative predictive value was predicted. The value was 94.7%; the EGFR mutation rate in the positive and negative expression of Napsin A was 63%, 4.5%, and the difference was statistically significant (P=0.000). The sensitivity of EGFR mutation was 98.9%, the specificity was 29.2%, the positive predictive value was 63%, the negative predictive value was 95.5%, the EGFR mutation rate of the double positive expression of two was 65.4%, and two predicted EGF. The sensitivity of the R mutation was 98.9%, the specificity was 36.1%, the positive predictive value was 65.4%, the negative predictive value was 96.3%. conclusion: 1. in the lung adenocarcinoma, the EGFR mutation was higher, more seen in exon 19,21, women, non smoking, high tissue differentiation can predict the high EGFR mutation rate of lung adenocarcinoma patients; 2.TTF-1 and Napsin A in the lung adenocarcinoma tissue High level, two significant correlation, can be used as a reference index for diagnosis of lung adenocarcinoma, especially in women, non smoking, highly differentiated lung adenocarcinoma patients, 3. lung adenocarcinoma tissue TTF-1 and Napsin A expression and EGFR mutation has a good correlation, the level of expression of the two can predict EGFR mutation state, and TTF- 1 the combined expression of Napsin and A may have a higher EGFR mutation, which can provide a reference value for targeted therapy in clinical lung adenocarcinoma patients.
【学位授予单位】：皖南医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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