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Eepidermal Growth Factor Receptor Mutations Of Lung Tissue And Metastatic Lymph Node In Patients With Non-small Cell Lung Cancer

Posted on:2008-12-22Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z ChenFull Text:PDF
GTID:1114360275487085Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Lung cancer is a common fatal disease with highestmobidity and motality rate among tumors in urban China.With thedevelopment of standard platinum-based chemotherapy regimens andDocetaxel-based second line regimen,the 5-year survival remainspoor in non-small cell lung cancer (NSCLC).Epidermal growth factorreceptor (EGFR) tyrosine kinase inhibitor provides a noveltreatment for advanced non-small cell lung cancer(NSCLC).Gefitinib isa strong epidermal growth factor receptor (EGFR) tyrosinekinase inhibitor,which blocks the activity of EGFR by competes ATPbinding site on EGFR with ATP.So it is interesting evaluate therelationship of EGFR and tyrosinekinase inhibitor.Recently,two groups reported that the mutation rate of tyrosinekinase domain of EGFR was much higher among gefitinibresponders than non-responders,and Japanese has highermutation rate than American.There is a regionaldifference for EGFR mutation.Mutation rates were higheramong gefitinib responders,non-smokers,patients withadenocarcinoma or female patients.Objective To analyze theincidence and profile of mutations in epidermal growth factorreceptor (EGFR) in patients with cell lung cancer (NSCLC).Methods:A total of 24 cases of non-small cell lung cancertissue was enrolled in this study,among which 24 normallung samples and 21 lymph node were also included.The tissueDNA was extracted and the EGFR gene in exon 19 to 21was subjected for PCR amplification and direct sequencing.Results The EGFR gene in exon 19-21 was of wild typein all normal lung tissues detected.Mutations were found in5 cases of 24 lung cancer samples,with an incidence of20.8%.Mutations were mainly detected in the exon 21 (4/24cases,16.6%) and exon 19 (1/24 cases,4%),resulting inthe deletion of codon 746 to 753.The mutation in exon 21belonged to the single missense substitution in codon 858.The EGFR mutations were more frequent in adenocarcinomaand adenosquamous cell carcinoma versus cancer ofother histologies.There was no statistically significantdifference between the mutation with gender and age.Mutations were found in lcase of 21 lymph node samples,withan incidence of 4.8%.The type of mutation weresimilar between primary and corresponding metastatic lymphnode,and the mutation detected in metastatic tumors wasalso detected in the corresponding primary tumors.On theother hand,in 4 of the 5 cases,there were mutation detected onlyin primary tumors.Conclusion:EGFR mutation is atumor-specific somatic abnormality.Some one fifth of ChineseNSCLC tumors harbor EGFR mutations,especially in exons 21 and19.These mutations are more frequently detected inadenocarcinoma and adenosquamous cell carcinoma.EGFRmutations detected in lymph node samples may predict theEGFR mutations of NSCLC partially.
Keywords/Search Tags:Lung neoplasm, Carcinoma, non-small cell lung, Epidermal growth factor receptor, Gene, Mutation, Lymph node
PDF Full Text Request
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