Detection Of EGFR Gene Mutations And Its Clinical Significance In The Pleural Effusion Of Advanced Non-small-cell Lung Cancer Patients

Background:Epidermal growth factor receptor(EGFR) is an important molecule target in targeted therapy for non-small-cell lung cancer(NSCLC).EGFR tyrosine kinase inhibitors(TKIs)gefitinib and erlotinib block the activity of EGFR-TK by competing ATP biding site on EGFR,and It is the new way for the treatment of advanced NSCLC.It had reported that the mutation rates of EGFR gene were much higher for those gefitinib responders than non-responders.Patients with EGFR mutation had hypersensitivity to the EGFR tyrosine kinase inhibitors.Almost 90%of EGFR mutations were located in exon 19 and exon 21 of EGFR gene,all of which were heterozygous mutation and activating mutation.Now most EGFR gene mutations have been detected from tissue samples,but sometime it is difficult to obtain tumor samples,especially in patients with inoperable NSCLC,it is necessary to find different samples to detect EGFR gene. Objective:To evaluate the mutation in exon19 and exon21 of EGFR gene in pleural effusion of advanced NSCLC and to explore the relationship between EGFR gene mutation of malignant pleural effusion(MPE) and efficacy of EGFR-TKIs in advanced NSCLC patients.Methods:We collected 23 samples of MPE from advanced NSCLC patients.The pleural effusion fluid was centrifuged, and cellular components obtained were used for detection.EGFR gene mutations were detected by nested PCR and direct sequencing.Results:The activating EGFR tyrosine kinase domain mutations were detected in 8(34.8%) patients out of the 23 patients of MPE.Four mutations were deleted mutations located in exon 19,two were substituted mutations located in exon 21 and two were combining mutations located in exon 19/21 and exon 20/21 respectively.The EGFR mutations were observed more frequently in non-smoker(P＜0.05).For female patients there were 50%mutations and for male patients there were 29.4% mutations,but the differences between gender were not statistically significant.Response rates and disease control rates in patients were 25%and 75%respectively.Patients with EGFR gene mutation had a higher disease control rate than those without mutations(P＜0.05).As our samples were small,we did not evaluate the difference of response rates between those patients with EGFR gene mutations and those without mutations.Conclusion:The main mutations of EGFR gene in MPE were in-frame deletions in exon 19 and the substitution mutations in exon 21.EGFR mutation status may be useful for predicting responsiveness to EGFR-TKI.The pleural effusion fluid can be used to detect EGFR gene mutation.