The Relationship Between Epidermal Growth Factor Receptor (EGFR) Mutation And Histologic Subtype According To New Classification (IASLC/ATS/ERS In 2011) And Clinical Characteristics In Stage?lung Adenocarcinoma

Background and Objective: To investigate the relationships between epidermal growth factor receptor(EGFR)mutations and histologic subtypes of lung adenocarcinomas and clinical characteristics according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciulinary classification of lung adenocarcinoma.Methods: 100 surgically resected lung adenocarcinomas' histologic subtypes with I stage according to the new classification of lung adenocarcinomas involved in this study.Next-generation sequencing(NGS)was performed to detect status of mutation of exon19 and exon21 of EGFR gene based on Ion Torrent PGMTM.Correlation analysis(X2)method was used to investigate the correlation between histologic subtypes and clinical characteristics and EGFR mutations in stage?lung adenocarcinoma.Results: The most prevalent subtype was acinar predominant adenocarcinoma(APA)with a total of 45 cases(45.0%,45/100),followed by lepidic predominant adenocarcinoma(LPA)with 36 cases(36.0%,36/100),solid/mucinous predominant adenocarcinoma(SPA/MA)with 9 cases(9.0%,9/100),papillary predominant adenocarcinoma(PPA)with 8 cases(8.0,8/100),micropapillary predominant adenocarcinoma(MPA)with 2 cases(2.0,2/100).Among 100 patients with lung adenocarcinoma,EGFR mutations were found in 49 cases(49.0%).The mutated exons included classic exon19(38.8%,19/49)and classic exon21(61.2%,30/49).Amoung all histologic subtype,EGFR mutation were found in lepidic predominant adenocarcinoma with 23 cases(63.9%,23/36),papillary predominant adenocarcinoma with 5 cases(62.5%,5/8),acinar predominant adenocarcinoma(APA)with 21 cases(46.7%,21/45).EGFR mutation were not found in micropapillary predominant adenocarcinoma and solid/mucinous predominant adenocarcinoma.EGFR mutations were significantly associated with histologic subtypes in lung adenocarcinomas with stage I(P = 0.002).Especially,the frequency of EGFR mutations in lepidic predominant adenocarcinoma(63.9%,23/36)were higher than that in nonlepidic predominant adenocarcinoma(36.7%,18/49)P = 0.018,whereas the frequency of EGFR mutation in solid/mucinous predominant adenocarcinoma(20.0%,3/15)was lower than that in nonsolid/mucinous predominant adenocarcinoma(54.1%,46/85)P = 0.015.EGFR mutation were also associated with differentiation of patients with lung adenocarcinoma(P = 0.001),and no correlation of EGFR mutations with gender,age,smoking,tumor size,pleural invasion(all P > 0.05).Conclusions: The most prevalent subtype was acinar predominant adenocarcinoma(APA)with a total of 45 cases(45.0%,45/100).In stage ? lung adenocarcinomas,those with lepidic predominant adenocarcinoma or the presence of lepidic component have higher frequency of EGFR mutation.The degree of differentiation is related to EGFR mutation.