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Detection Of EGFR Gene Mutations In The Pleural Effusion Of Lung Cancer Patients And The Relationship With The Therapeutic Efficacy Of Targeted Drugs

Posted on:2014-12-18Degree:MasterType:Thesis
Country:ChinaCandidate:Q WangFull Text:PDF
GTID:2254330398965257Subject:Respiratory Internal Medicine
Abstract/Summary:PDF Full Text Request
Background: Lung cancer is a serious threat to human health, whose morbidity andmortality is the highest in malignant tumor, and non-small-cell lung cancer takes aproportion of75percentage to80percentage. Though obvious improvement has beenachieved in diagnostic of lung cancer, most of lung cancer patients were diagnostic asadvanced stage, have lost the best time operation, only can receive the chemical drug andradiation therapy. The side effect of chemical drug and radiation therapy is serious, somepatients can not tolerate it. Recently, the targeted drugs have provided a new hope for lungcancer patients. Targeted drugs as a kind of low molecular compounds taking convenientand having small side effects, but there are individual differences in different patient. A lotof studies have showed a link between somatic mutation of the Exon18to21in EGFRgene and the responses to targeted drugs. Further study found that almost90percentage ofEGFR mutations were located in exon19and exon21of EGFR gene. Now, most EGFRgene mutations were detected from tissue samples, but sometimes they are difficult toobtain tumor samples, especially in patients with inoperable non-small-cell lung cancer, soit is necessary to find some other samples that easily get to detect EGFR gene mutation.Objective: To explore the mutation in exon19and exon21of EGFR gene in pleuraleffusion of non-small-cell lung cancer, and evaluated the correlation between the EGFRgene mutation and the therapeutic response to targeted drugs.Methods: Collected45cases malignant effusion specimens of non-small-cell lungcancer patients, including34cases from the patients who first receive treatment and11cases of progress after treatment. All of the pleural effusion fluid was centrifuged anddivided into two parts. One part was for cell embedding, looking for tumor cells, the otherwas cryopreserved for EGFR detection. EGFR gene mutations were detected by nested PCR and direct sequencing.Results:34cases from the patients who first receive treatment and11cases ofprogress after treatment, cell embedding looking for tumor cells. There are24cases findtumor cells in34cases (70.5%,24/34),8cases find tumor cells in11cases(72.7%,8/11).Detect EGFR gene of exon19and21in24cases of the patients who firstreceive treatment, there are5cases mutations were located in exon19and3casesmutations were found in exon21.In8cases patients of progress after treatment, thereare3cases located in exon19and1case in exon21. The tumor cells detection rate was71.1%(32/45);the mutation rate of EGFR was37.5%(12/32);the exon19and21mutationrate was66.6%(8/12) and33.3%(4/12) respectively. There are24patients received targeteddrugs(including the12cases EGFR gene mutation patients),the disease control rate was70.8%(17/24). The differences between gender, age and smoking status were notremarkable. Objective response rates and disease control rates in EGFR gene mutationpatients were58.3%and83.3%, higher than the patient with wild EGFR gene.Conclusion1. Detect the mutations of exon19and exon21of EGFR gene in pleural effusions oflung cancer patients by direct sequencing is available for clinical application.2. The mutation rate of EGFR gene of Exon19and Exon21was66.6%and33.3%respectively, and the Exon19mutation of EGFR gene was more common in the patientswith lung cancer.3. There are relationship between the EGFR gene mutation and the therapeutic responseto targeted drugs. The objective response rates can be higher in patient who with sensitiveEGFR gene mutation with targeted drugs.
Keywords/Search Tags:lung cancer, EGFR, gene mutation, targeted treatment
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