The Relationship Between The Expression Of TTF-1,Napsin A And EGFR,ALK Mutations And Clinical Features In Lung Adenocarcinoma

Background and purposeAt present,the average morbidity and mortality of primary lung cancer are the highest in the world.Lung adenocarcinoma is a common type of primary lung cancer,accounting for about 30%of all lung cancers.Epidermal growth factor receptor(EGFR)gene and anaplasia lymphoma kinase(ALK)gene mutations are common driver gene mutations in lung adenocarcinoma and have become important targets for the therapy of advanced lung adenocarcinoma.However,genetic testing is cumbersome,expensive and requires a high-level laboratory.Is it possible to look for some easily available indicators associated with these mutations to predict gene status or guide genetic testing?Thyroid transcription factor-1(TTF-1)and novel aspartic proteinase A(Napsin A)are both expressed in lung adenocarcinoma and are often used in the diagnosis and differential diagnosis of lung adenocarcinoma.The relationship between TTF-1,Napsin A and EGFR mutation has been mentioned in some literatures,but the conclusions are different.Some literatures have shown that ALK mutations are rare in patients with TTF-1 negative,but the relationship between them has not been studied.Besides,the relationship between Napsin A and ALK mutation has not been studied at home and abroad.Therefore,this study discussed the relationship between the expression of TTF-1,Napsin A and the mutation of EGFR,ALK genes and its clinical predictive value,and analyzed the relationship between the expression of TTF-1,Napsin A and the clinical characteristics of patients.MethodsThis study was a retrospective study.227 lung adenocarcinoma patients who were admitted to First Afiliated Hospital of Zhengzhou University from January 2018 to December 2018 were included.Collecting the clinical data(including hospitalization number,name,gender,age,smoking history,drinking history,TNM stage,maximum diameter of tumor,distant metastasis).The results of TTF-1 and Napsin A in lung adenocarcinoma tissues were obtained by EnVision two-step method in the pathology department of our hospital.The detection of EGFR gene was performed by the pathology department of our hospital using real-time fluorescence PCR,DNA sequencing or second-generation sequencing technology.The detection of ALK gene was performed by fluorescence in situ hybridization,enhanced immunohistochemistry or reverse transcription polymerase chain reaction in pathology department.SPSS 21.0 statistical software was used to analyze the relationship between the expression of TTF-1,Napsin A and EGFR,ALK gene mutations and patients’ clinical characteristics.The sensitivity,specificity,positive predictive value and negative predictive value of TTF-1,Napsin A,TTF-1 in series with Napsin A,and in parallel with Napsin A for EGFR mutation prediction were calculated,and their predictive value and clinical significance for EGFR gene mutation were analyzed.Results1.TTF-1 was detected in 227 patients,among which 193(85.0%)were positive,while Napsin A was detected in 165 patients,among which 126(76.4%)were positive.EGFR gene was detected in 227 patients,57(25.1%)of exon 19 mutations,6(2.6%)of exon 20 mutations,58(25.6%)of exon 21 mutations,3(1.3%)of exon 18 and 20 mutations,1(0.4%)of exon 18 and 21 mutations,6(2.6%)of exon 19 and 20 mutations,2(0.9%)of exon 19 and 21 mutations,and 2(0.9%)of exon 20 and 21 mutations.There were a total of 135(59.5%)mutations cases.A total of 216 patients were tested for ALK gene mutation,and 10 patients(4.6%)had ALK gene mutation.2.There was no significant difference in TTF-1 expression rate among different age groups(P>0.05).The positive expression rate of TTF-1 in female patients was higher than male patients,non-smokers was higher than smokers,non-drinkers was higher than drinkers,and the difference was statistically significant(P<0.05);there was no significant difference in the positive expression rate of Napsin A in different age groups(P>0.05).The positive expression rate of Napsin A in female patients was higher than male patients,non-smokers was higher than smokers,non-drinkers was higher than drinkers,and the difference was statistically significant(P<0.05).3.The expression of TTF-1 was correlated with adrenal metastasis,contralateral lung metastasis and tumor diameter(P<0.05),but not with pleura metastasis,bone metastasis,brain metastasis,liver metastasis and TNM stage(P>0.05).The positive expression rate of TTF-1 was higher in patients without adrenal metastasis,with contralateral lung metastasis or tumor diameter<3cm.The expression of Napsin A was correlated with contralateral lung metastasis and tumor diameter(P<0.05),but not with pleura metastasis,adrenal metastasis,bone metastasis,brain metastasis,liver metastasis and TNM stage(P>0.05).The positive expression rate of Napsin A was higher in patients with contralateral lung metastasis or tumor diameter ≤3cm.4.The mutation rate of EGFR in TTF-1 positive patients was higher than that in negative patients(68.4%vs 8.8%),the difference was statistically significant(P<0.05).The mutation rate of EGFR in patients with Napsin A positive was higher than that in negative patients(67.5%vs 12.8%),the difference was statistically significant(P<0.05).5.There was no statistically significant difference in ALK gene mutation rate between TTF-1 positive patients and TTF-1 negative patients(P<0.05);there was no statistically significant difference in ALK gene mutation rate between Napsin A positive patients and Napsin A negative patients(P<0.05).6.The sensitivity,specificity,positive predictive value and negative predictive value of EGFR mutation predicted by TTF-1 were 97.8%,33.7%,68.4%and 91.2%respectively.The sensitivity,specificity,positive predictive value and negative predictive value of EGFR mutation predicted by Napsin A were 94.4%,45.3%,67.5%and 87.2%respectively.The sensitivity,specificity,positive predictive value and negative predictive value of EGFR mutation predicted by Napsin A and TTF-1 in parallel were 97.8%,33.3%,63.8%and 92.6%respectively.The sensitivity,specificity,positive predictive value and negative predictive value of EGFR mutation predicted by them in series were 94.4%,48.0%,68.5%and 87.8%respectively.Conclusions1.In lung adenocarcinoma patients,TTF-1 positive expression rate was higher in the female,non-drinking,non-smoking,non-adrenal metastasis,contralateral lung metastasis or whose tumor diameter≤3cm.The positive expression rate of Napsin A was higher in the female,non-drinking,non-smoking,contralateral lung metastasis or whose tumor diameter≤3cm.2.The mutation rate of EGFR gene was higher in lung adenocarcinoma patients with TTF-1 positive or Napsin A positive,and there was no correlation between the mutation of ALK gene and expression of TTF-1,Napsin A.TTF-1,Napsin A may become factors for predicting EGFR gene mutation in patients with lung adenocarcinoma.