Invastigation Of The Relationship Between Radiographic Characteristics,pathological Classification Of Early Lung Adenocarcinoma Manifested With Nodule And Abnormality Of Multiple Driver Genes

Objective : To investigate the relationship between the radiographic characteristics,pathological classification of early lung adenocarcinoma manifested with nodule and the common driver genes epidermal growth factor receptor(EGFR),echinoderm microtubule-associated protein anaplastic lymphoma kinase Echinoderm microtubuleassociated protein-like 4-anaplastie lymphoma kinase,EML4-ALK),c-ROS oncogene 1 receptor tyrosine kinase(ROS1),kirsten rat sarcoma viral oncogene,KRAS)mutations.Methods:A total of 40 patients in our hospital of early lung adenocarcinoma manifested with nodule who underwent surgical resection were enrolled and compared with 10 cases of benign pulmonary nodules in the study.The clinical data and radiographic data of the patients were collected.The expression of EGFR,EML4-ALK,ROS1 and KRAS of paraffin specimens detected by Amplified Block Mutation System(ARMS)was analyzed,and the relationship between different imaging features and pathologic type and gene mutation was analyzed.RESULTS: There were 5 cases of adenocarcinoma in situ(AIS),10 cases of microinvasive adenocarcinoma(MIA)and 25 cases of invasive adenocarcinoma(IA)in 40 cases of early adenocarcinoma with nodules.A total of 31 cases of driver gene abnormalities were detected in 40 cases of early lung adenocarcinoma with a total mutation rate of 77.5%,of which 26 cases were EGFR mutation(mutation rate was 62.5%,including of 17 cases of L858 R,8 cases of 19 Del and 1 case of L861 Q / G719 A / G719C),ALK Mutation in 3 cases(mutation rate 7.5%),KRAS mutation in 3 cases(mutation rate 7.5%),ROS1 mutation in 0 case,and quadruple negative patients in 9 cases,we haven’t detected patients with EGFR mutation coexisting with ALK,KRAS or ROS1 mutations.There was a clear correlation between the pathological type of early lung adenocarcinoma and nodular edge irregularities,pleural indentation,nodular density and size(p <0.05).SUVmax> 2.5 and SUV metabolic index ≧1.2 were positively correlated with nodule size(r = 0.504,p = 0.014;r = 0.571,p = 0.004 respectively).Nodules with irregular edges,vascular insertion and solid density had higher SUVmax(p <0.05).The mutations of four driver genes were closely related to the nodule size,pleural indentation,nodule density and histological classification(p <0.05).EGFR mutation was closely related to the latter three(p <0.05).Invasive lung adenocarcinoma had higher SUVmax and SUV metabolic index(p <0.05).Conclusion: Early lung adenocarcinoma showed a very high driver gene abnormalities with four gene abnormalities reached to 77.5%.Genetic abnormalities were positively correlated with maging findings suggest that lung adenocarcinoma imaging changes such as nodular irregular edge,pleural indentation,increased density and increased nodules size.The detection rate of abnormality of the four genes increases with the development of early stage of lung adenocarcinoma,suggesting that early driver genes of nodular lung adenocarcinoma plays an important role in the early occurrence and development of lung adenocarcinoma with nodules.Early stage lung adenocarcinoma with nodules need for more refined genetic analysis in addition to pathological classification,which may help early diagnosis and guide subsequent treatment.