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Mutations In EGFR Gene Associated With Tyrosine Kinase Inhibitor Response In Advanced Non-small-cell Lung Cancer

Posted on:2011-08-09Degree:MasterType:Thesis
Country:ChinaCandidate:J W ChengFull Text:PDF
GTID:2154360305998023Subject:Surgery
Abstract/Summary:PDF Full Text Request
OBJECTIVE:To investigate the correlation between mutation in EGFR tyrosine kinase domain and tumor response as well as prognosis in advanced stage non-small cell lung cancer (NSCLCs) treated with Tyrosine kinase inhibitor.METHOD:This study included 37 patients with stageâ…¢B/â…£non-small-cell lung cancer who treat with Tyrosine kinase inhibitor. Cancer tissue was obtained from these patients, and DNA was extracted for analysis of mutation in exon 18 to 21 of EGFR. Exon 18 to 21 of EGFR were amplified by PCR (Polymerase Chain Reaction), sequenced and analysis from both sense and antisense directions.RESULTS:In all 37 patients with stageâ…¢B/â…£non-small-cell lung cancer 11 cases (29.7%) EGFR mutations were detected, In which 2 cases mutation in exon 18,7 cases mutation in exon 19,2 cases mutation in exon 21.Mutation was found to be more frequent in the adenocarcinoma(35.7%)than in the non-adenocarcinoma (11.1%,P=0.023). Mutation also was found to be more frequent in the female (38.8%)and non-somke(33.3%)than in the male(21.1%)and smoke(20.0%, P=0.03,P=0.069, respectively).Response rate to Tyrosine kinase inhibitor was (81.8%)in the patients with EGFR mutation versus(15.4%)in those without mutation(P<0.01).Compared with the patients without EGFR mutation, those with mutation had longer overall survival(median,15.1 VS 3.1 months, P<0.01)and median time to prognosis (median,18.6 VS 6.1 months, P<0.01).CONCLUTION:NSCLCs patients with EGFR mutations mainly occur in exon 19. Adenocarcinoma, women patients have the high mutation rate compare to non-adenocarcinoma, male patients. Logistic regression analysis showed that response was primarily linked to the presence of EGFR mutations and secondarily linked to female gender status.The presence of EGFR mutations is a major determinant of Tyrosine kinase inhibitor response, and EGFR mutation should be analysised before tyrosine kinase inhibitor for patients with advanced NSCLCs.
Keywords/Search Tags:Tyrosine kinase inhibitors, epidermal growth factor receptor, gene mutation, non-small-cell lung cancer, prognosis
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