title: Biological characteristics and epidermal growth factor receptor tyrosine kinase inhibitors efficacy of EGFR mutation and its subtypes in lung adenocarcinoma.
abstract: Mutation of epidermal growth factor receptor (EGFR) gene has been reported to be present in lung adenocarcinoma (LAC). In this study, we extensively investigated the impact of patients' biological characteristics on EGFR mutation and the impact of EGFR mutation subtypes on targeted therapy of advanced LAC. We examined EGFR exons18to21status in169 LAC patients by direct sequencing to study the impact of patients' biological characteristics on the EGFR mutational spectrum. And then, 59 patients with advanced LAC harboring EGFR exon 19 deletions(del 19) or exon 21 point mutation(L858R) mutations received first-line treatment of gefitinib or erlotinib, the efficacy of treatment, and the progression-free survival (PFS) of these patients were recorded. The frequency of the EGFR mutation and its subtypes and the variables associated with the EGFR mutation after removing the confound factors were investigated by the logistic analysis using all samples (n = 169). The EGFR mutation was significantly associated with well-differentiated tumor and excessive household cooking fumes(P < 0.05). The deletions in exon 19 were more frequently associated with well-differentiated tumor (P < 0.05). The overall frequency of the EGFR mutation was 49 %. Then the impact of EGFR mutation subtypes on targeted therapy were investigated by the retrospective analysis on 59 advanced LAC patients with del 19 or L858R mutations and treated first-line with erlotinib or gefitinib. The deletions in exon 19 got longer PFS (P < 0.05). But there were no differences in PFS between erlotinib therapy and gefitinib therapy. EGFR mutations were more frequently in high tumor differentiation and excessive household cooking fumes LAC. The del 19 mutation rate is relatively high with a high differentiation degree in advanced lung adenocarcinoma. The deletions in exon 19 may benefit more from first-line targeted therapy of advanced LAC compared with exon 21 point mutation L858R. There was no significant difference between the efficacy of gefitinib and erlotinib treatments associated with EGFR mutation and its subtypes.
authors.affiliation: Department of Respiratory, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
authors.forename: Rong-Li
authors.initials: RL
authors.lastname: Lu
authors.forename: Cheng-Ping
authors.initials: CP
authors.lastname: Hu
authors.forename: Hua-Ping
authors.initials: HP
authors.lastname: Yang
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.forename: Qi-Hua
authors.initials: QH
authors.lastname: Gu
authors.forename: Lielin
authors.initials: L
authors.lastname: Wu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005091:Exons / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib