The Correlation Between TTF-1 And Napsin A Expression And EGFR Mutations In Lung Adenocarcinoma

Objective: At present,the key to the benefit of molecular targeted therapy in patients with lung adenocarcinoma is to detect EGFR gene before treatment,understanding gene mutations,however,the process is complicated,the cost is high and false negative,so that some patients lose the chance of detection and delay treatment.Therefore,it is necessary to find new indicators related to EGFR gene mutations to predict the mutations to guide the treatment.Thyroid transcription factor-1(TTF-1)and aspartic proteinase A(Napsin A)as a diagnostic index of patients with lung adenocarcinoma,often using immunohistochemical determination,the method is more efficient and convenient than the method of detecting EGFR gene mutations.Based on this,the expression of TTF-1 and Napsin A in lung adenocarcinoma were detected by immunohistochemica staining and EGFR mutations were detected by ARMS method in this study,and to investigate the expression of both of them in lung adenocarcinoma tissue and EGFR mutations status and clinical predictive value.Method: The 160 cases of primary lung adenocarcinoma patients with EGFR testing results were collected that were confirmed by histopathology in the department of Pathology,Yijishan Hospital of Wannan Medical College from March 2014 to June2016.All cases didn,t rceive preoperative radiotherapy and chemotherapy before the cases were taken,and the clinical fllow-up data was available.All clinical data of patients access to previous medical records from the hospital library,including age,gender,smoking status,tissue differentiation degree,and clinical staging.All the specimens were fixed in 10% neutral buffered fbraialin paraffin-embedded,hematoxylin-eosin staining and then reviewed to confirm the diagnoses by two pathologists before immunohistochemisty test.Immunohistochemical stain for TTF-1and Napsin A was performed by En Visio method and EGFR mutations status were detected by ARMS.Statistic Analysis was performed by using the SPSS 18.0 statistical software,and count data was analyzed by ?2test.P<0.05 was defined as statistic significant difference.Results : 1.EGFR mutations rate was 55% in the group of lung adenocarcinoma patients,which mainly occurred in exon 19 and exon 21,accounting for about 52.3%of exon 19 and 43.1% of exon 21.women(P=0.001),nonsmokers(P=0.026)and high degree of tissue differentiation(P=0.021)were found to be significantly associated with the incidence of EGFR mutations;2.The positive expression rates of TTF-1 and Napsin A in lung adenocarcinoma were 88.1% and 86.3%,respectively,positive expression rate of both was 83.1%,there was no association among age and TNM stage(P>0.05),howerer,there was closely related with gender(P=0.012,P=0.035),smoking(P=0.018,P=0.036)and the degree of differentiation(P=0.013,P=0.009).The two had a significant positive correlation(Kappa coefficient=0.637,r=0.639,P=0.000)),the expression of TTF-1 and Napsin A was significantly higher in women,nonsmokers and high degree of tissue differentiation of lung adenocarcinoma patients;3.The expression of TTF-1 and Napsin A was positively correlated with EGFR mutation(r=0.367,P=0.000,r=0.405,P=0.000),the rate of EGFR mutations in positive and negative expression of TTF-1 were 61.7%,5.3%,the difference was statistically significant(P=0.000),the sensitivity of TTF-1 to predict EGFR mutations was 98.9%,specificity was 25%,positive predictive value was 61.7%,negative predictive value was 94.7%;the rate of EGFR mutations in positive and negative expression of Napsin A were 63%,4.5%,the difference was statistically significant(P=0.000),the sensitivityof Napsin A to predict EGFR mutations was 98.9%,specificity was 29.2%,positive predictive value was 63.0%,negative predictive value was 95.5%;the rate of EGFR mutations in positive expression of both were 65.4%,the sensitivity of jointing them to predict EGFR mutations was 98.9%,specificity was 36.1%,positive predictive value was 65.4%,negative predictive value was 96.3%.Conclusion:1.EGFR mutations are higher in lung adenocarcinoma,which mainly occurred in exon 19 and exon 21,women,nonsmokers and high degree of tissue differentiation are found to be significantly associated with the incidence of EGFR mutations;2.The expression levels of TTF-1 and Napsin A are higher in lung adenocarcinoma tissues,them have significant positive correlation,which can be used as a reference index for the diagnosis of lung adenocarcinoma,also,positive TTF-1 and Napsin A staining are found to be significantly associated with women,nonsmokes and high degree of tissue differentiation;3.TTF-1 and Napsin A expression have a good correlation with EGFR mutations in lung adenocarcinoma,and TTF-1 is associated with Napsin A expression with higher EGFR mutations possible,which may provide reference value for targeted therapy of lung adenocarcinoma patients.