Preliminary Study On Genomic Characteristics Of Lung Adenosquamous Carcinoma

Objective:Lung adenosquamous carcinoma was detected to observe its clinicopathological features,genomics characteristics.Provide genomics research data for clinical diagnosis and treatment of patients with LASC.Methods:Surgical resection specimens of 21 cases of LASC without preoperative chemoradiotherapy,which the squamous cell carcinoma components and adenocarcinoma components accounted for more than 10%based on WHO,which were identified by two experienced pathologists.HE and immunohistochemical P63,P40,NapsinA,TTF1 for auxiliary diagnosis.To use microdissection to separate squamous cell carcinoma and adenocarcinoma components from lung adenosquamous carcinoma,using a large Panel containing more than 1000 lung cancer variant genes,of 21 cases LASC gene mutations were detected,and the tumor phylogenetic tree of LASC were delineated.Preliminary exploration of its genomics characteristics.Result:(1)Clinicopathological features of lung adenosquamous carcinoma,of the 21cases,7 were males,14 were females.3(14.3%)were smokers,18(85.7%)were nonsmokers.Stages T1-T2,T3-T4 were 17(81%),4(19%)cases.The overall lymph node metastasis rate was 57%(12/21),mainly were adenocarcinoma,of the 12 cases,adenocarcinoma,squamous cell carcinoma,adenosquamous carcinoma were discovered in 6(50%),2(16.7%),4(33.3%)cases,respectively.(2)Analysis of neoplastic tree,delineating the tumor phylogenetic tree of 21 cases with lung adenosquamous carcinoma,20 were trunk mutations,1 case were no trunk mutation,confirmed that lung Adenosquamous carcinoma is mostly of monoclonal origin.(3)Among the 21 lung adenosquamous carcinoma samples,the highest frequency gene mutation,including 17(81%)with EGFR mutations,15(71%)with TP53 mutations,4(19%)with RB1mutations,4(19%)with TERT mutations,4(19%)with SMARTA4 mutations,and 2(14%)with MAP3K1 mutations.(4)Comparison of gene mutation profiles between adenocarcinoma component(ACC)and squamous cell carcinoma component(SCCC)in 21 cases of lung adenosquamous carcinoma.Although TP53 appears to account for a higher proportion of SCCC,it does not reach statistical significance(P>0.05).In addition,no statistical differences were found,probably because of the small sample size.(5)The difference in the mutational spectrum between ACC and the LAC database of Gene~+-Beijing(n=170),three differential genes were found,the mutation rate of EGFR in ACC was significantly higher than LAC(81%vs 56%;P=0.035)and the incidence of mutations in EZH2 and MAP3K1 was also significantly higher than LAC(P=0.032).In addition,no statistical differences were found.(6)ACC was compared with LAC database of Gene~+-Beijing.EGFR in SCCC was significantly higher than LSCC(76%vs 11%;P<0.001).In addition,no statistical differences were found.Conclusion:Lung adenosquamous carcinoma is mostly of monoclonal origin.It has its unique genomic and clinical pathological features,especially with high EGFR mutations.EGFR mutation detection and targeted therapy may play an important role in the treatment of LASC patients.