Classification of epidermal growth factor receptor gene. Epidermal growth factor receptor egfr mutations are observed in. A rapid and sensitive enzymatic method for epidermal growth. Costeffectiveness of epidermal growth factor receptor mutation testing and firstline treatment with gefitinib for patients with advanced adenocarcinoma of. Epidermal growth factor receptor mutation analysis in cytological.
Analysis of epidermal growth factor receptor mutations predicts. We conducted this study to verify the feasibility of egfr mutation analysis in cytological specimens and investigate the responsiveness to. Epidermal growth factor receptor egfr is a transmembrane protein that functions as a receptor for members of the epidermal growth factor family, the overexpression of which plays a critical role in. Epidermal growth factor receptor egfr mutation represents a good response to egfrtyrosine kinase inhibitor and an advantageous prognostic factor in advancedstage nonsmall cell lung. Ct graylevel texture analysis as a quantitative imaging biomarker of epidermal growth factor receptor mutation status in adenocarcinoma of the lung efe ozkan1 anna west1 jeffrey a. Epidermal growth factor receptor mutations in lung cancer. Epidermal growth factor receptor egfr belongs to a family of growth factor receptors involved in normal growth. Computational analysis of epidermal growth factor receptor. Epidermal growth factor receptor mutations and gene. Thus, early detection of the egfr mutation rate and its associated factors in lung tumors may present an important reference to individualize clinical treatment and improve treatment implementation in lung cancer, as well as to reduce the toxicity of drugs. Otterson5 konstantin shilo3 subha ghosh1 mark king1 richard d. In this study, we validated egfr mutation detection using highresolution melting analysis hrma and evaluated the associations between egfr mutations and clinical outcomes in advanced. In many cancer types, mutations affecting egfr expression or activity could result in cancer.
Epidermal growth factor receptor egfr mutations, especially deletional mutations in exon 19 del and l858r, predict gefitinib sensitivity in patients with nonsmall cell lung cancer nsclc. The impact of epidermal growth factor receptor mutations on. Epidermal growth factor receptor mutations in needle biopsy. The aim of the present study was to investigate the mutation rate of the epidermal growth factor receptor egfr in nonsmall cell lung cancer nsclc patients and to apply logistic regression analysis to investigate the factors associated with egfr gene mutation to provide data for the treatment of nsclc. Peripheral blood for epidermal growth factor receptor mutation. Kinetic analysis of epidermal growth factor receptor somatic. We conducted this study to verify the feasibility of egfr mutation analysis in. Screening for epidermal growth factor receptor mutations.
Epidermal growth factor receptor egfr is a transmembrane protein that is activated by binding of its specific ligands, including epidermal growth factor and transforming growth factor. Epidermal growth factor receptor mutation enhances expression. Epidermal growth factor receptor mutation as a risk factor. The presence of epidermal growth factor receptor egfr mutations is an. Ct graylevel texture analysis as a quantitative imaging. The egfr gene provides instructions for making a receptor protein called the epidermal growth factor receptor, which spans the cell membrane so that one end of the protein remains inside the cell and the.
Epidermal growth factor receptor egfr is expressed in 50% of nsclcs, and its expression is. Pretreatment epidermal growth factor receptor egfr t790m. Tumor epidermal growth factor receptor egfr mutation analysis is significant for making treatment decisions for metastatic pulmonary adenocarcinoma. The goal of this study was to determine the contribution of molecular alterations in egfr to response and survival within the. Epidermal growth factor receptor egfr mutations are observed in approximately 1015% of the caucasian population and more than 50% of the asian population with nonsquamous nonsmall cell lung cancer nsclc. Egfr a gene on chromosome 7p12 that encodes epidermal growth factor, a transmembrane glycoprotein of the protein kinase superfamily, which is a receptor for members of the epidermal growth factor family. Epidermal growth factor receptor egfr mutation is the key predictor of egfr. Mutations in the epidermal growth factor receptor egfr have recently. Plasma epidermal growth factor receptor mutation analysis and. The feasibility of performing egfr mutation testing using pleural fluid specimen is not well characterized.
Discordance of epidermal growth factor receptor mutation between. These articles were imported into an online software, covidence9 for study. Purpose most cases of nonsmallcell lung cancer nsclc with dramatic responses to gefitinib have specific activating mutations in the epidermal growth factor receptor egfr, but the. The epidermal growth factor receptor egfr is a member of the erbb family of receptor tyrosine kinases and is upregulated in many cancer cell types, including breast cancer and head and neck squamous cell carcinoma hnscc 36,62. Epidermal growth factor receptor mutation testing in. Full text detection of epidermal growth factor receptor mutation in.
Analysis of mutations in the gene for epidermal growth factor receptor egfr is considered medically necessary as a technique to predict treatment response for individuals with nonsquamous, nonsmall cell lung cancer when treatment with egfr tyrosine kinase inhibitor tki therapy is indicated. Epidermal growth factor receptor egfr is expressed in 50% of nsclcs, and its. However, not all epidermal growth factor receptor egfr mutations in tumor tissue dna. To retrospectively identify quantitative computed tomographic ct features that correlate with epidermal growth factor receptor egfr mutation in surgically resected lung adenocarcinomas stratified by the international association for the study of lung cancer iaslc, american thoracic society ats, and european respiratory society ers classification in an east asian cohort of. Epidermal growth factor receptor egfr has been considered a good candidate for targeted cancer therapy since its discovery. Increasing special drug designations to egfr inhibitors due to their high efficacy drives the growth of market brings great opportunities for the growth of market. Epidermal growth factor receptor mutation analysis in. To retrospectively identify quantitative computed tomographic ct features that correlate with epidermal growth factor receptor egfr mutation in surgically resected lung adenocarcinomas. Purpose patients with nonsmallcell lung cancer nsclc with epidermal growth factor receptor egfractivating mutations have excellent response to egfr tyrosine kinase inhibitors tkis, but t790m mutation accounts for most tki drug resistance.
Mutations in epidermal growth factor receptor and kras in. Risk factors of acquired t790m mutation in patients with. Activating mutations of the epidermal growth factor receptor egfr confer sensitivity. The presence of epidermal growth factor receptor egfr mutations is an established prognostic factor for patients with advanced lung adenocarcinoma. Here, we examined whether egfr mutation status is a prognostic factor for patients who had undergone surgery. A significant proportion of lung cancer patients carry mutations in the epidermal growth factor receptor egfr kinase domain. Epidermal growth factor receptor mutations in needle. Multivariate analysis for recurrencefree survival showed that ex19 was. Investigation of the epidermal growth factor receptor. Detection of epidermal growth factor receptor and human epidermal growth factor receptor 2 activating mutations in lung adenocarcimona by high. Comparison of epidermal growth factor receptor mutations between. Human egf is 6kda and has 53 amino acid residues and three intramolecular disulfide bonds.
We analysed egfr expression, egfr mutation status and gene expression profiles of prostate cancer pc to supply a rationale for egfr targeted therapies in this disease. Adequacy of malignant pleural effusion for epidermal. Human egf is 6kda and has 53 amino acid residues and three intramolecular disulfide. Adequacy of malignant pleural effusion for epidermal growth. A seminal study found that 57% of gbm specimens contain a mutation, rearrangement, splicing alteration, andor. A seminal study found that 57% of gbm specimens contain a mutation, rearrangement, splicing alteration, andor amplification of the epidermal growth factor receptor egfr. A modified extraction method of circulating free dna for. Circulating free dna cfdna in plasma is promising to be a surrogate for tumor tissue dna. Furthermore, the epidermal growth factor receptor egfr gene mutation is a predictor of gefitinib sensitivity in lung cancer 7,8. Epidermal growth factor receptor egfr mutation epidermal growth factor receptor also called her1 or erbb1 is a transmembrane receptor that controls the intracellular signal transduction pathways regulating proliferation, apoptosis, angiogenesis, adhesion and motility.
Epidermal growth factor receptor egfr activation has been shown to. The impact of epidermal growth factor receptor mutations. However, not all epidermal growth factor receptor egfr mutations in tumor tissue dna has been detected in matched cfdna, at least partly due to inefficient cfdna extraction method. Epidermal growth factor receptor egfr is one of the members of the erb.
Dec 18, 20 epidermal growth factor receptor egfr gene mutations g719x, exon 19 deletionsinsertions, l858r, and l861q predict favorable responses to egfr tyrosine kinase inhibitors tkis in advanced nonsmall cell lung cancer nsclc. Epidermal growth factor receptor expression and mutational analysis in synovial sarcomas and malignant peripheral nerve sheath tumors article pdf available in the oncologist 4. Epidermal growth factor receptor and kras gene mutation types. All statistical analyses were performed using ibm spss statistics 18 software. Comparison of epidermal growth factor receptor mutation statuses. This study assesses different technologies for detecting epidermal growth factor receptor egfr mutations from circulating tumor dna in patients with egfr t790m. The epidermal growth factor receptor is a member of the erbb family of receptors, a subfamily of four closely related receptor tyrosine kinases. Kinetic analysis of the purified intracellular domains of egfr l858r and egfr del746750 reveals that both mutants are active but. Activating mutations of the epidermal growth factor receptor egfr confer sensitivity to the tyrosine kinase inhibitors tki, gefitinib and erlotinib. The epidermal growth factor receptor protein is involved in cell signaling pathways that control cell division and survival. Epidermal growth factor receptor definition of epidermal. Radiological and clinical features associated with epidermal. Dynamic contrastenhanced mr imaging parameters in bone. Detection of epidermal growth factor receptor mutation in lung cancer by.
The quantalife software calculates the copy number of both mutant. Purpose patients with nonsmallcell lung cancer nsclc with epidermal growth factor receptor egfractivating mutations have excellent response to egfr tyrosine kinase inhibitors tkis, but. Definition of epidermal growth factor receptor nci. Epidermal growth factor receptor mutation detection using. Establishment of a novel method for screening epidermal. Kinetic analysis of epidermal growth factor receptor somatic mutant proteins shows increased sensitivity to the epidermal growth factor receptor tyrosine. Epidermal growth factor receptor mutation testing in the care of lung. Multiple ligands bind to the extracellular domain of the egfr and cause autophosphorylation and tyrosine kinase activity.
Realworld management of patients with epidermal growth. Epidermal growth factor receptor extracellular domain. Rapid detection of epidermal growth factor receptor mutations. Epidermal growth factor receptor egfr gene mutations g719x, exon 19 deletionsinsertions, l858r, and l861q predict favorable responses to egfr tyrosine kinase inhibitors. Costeffectiveness of epidermal growth factor receptor mutation testing and firstline treatment with gefitinib for patients with advanced adenocarcinoma of the lung. Screening for epidermal growth factor receptor mutations in. The preliminary results of our study showed a significant difference in dynamic contrast materialenhanced dce mr imaging parameters between bone metastases from epidermal growth. Epidermal growth factor receptor egfr gene mutation. B, images are segmented and graylevel texture analyses are performed on rois in each slice within given volume of interest voi. We have developed such software, which is able to perform pyrosequencing mutation data analysis for epidermal growth factor receptor. We show that two commonly occurring epidermal growth factor receptor egfr somatic mutations, l858r and an inframe deletion mutant, del746750, exhibit distinct enzymatic properties. Epidermal growth factor receptor egfr mutation is one of the.
Kinetic analysis of epidermal growth factor receptor. Peripheral blood for epidermal growth factor receptor mutation detection in. Recently, mutations in the epidermal growth factor receptor egfr gene in nonsmall cell lung cancer nsclc patients were reported to correlate with gefitinib response. The egfr gene provides instructions for making a receptor protein called the epidermal growth factor receptor, which spans the cell membrane so that one end of the protein remains inside the cell and the other end projects from the outer surface of the cell. Images obtained were analysed by the feature extraction software. Colorectal cancer is a model disease for egfrtargeted. Pdf epidermal growth factor receptor expression and.
The presence of a deletion mutation in exon 19 or l858r. Utilization of archived plasma to detect epidermal growth. Multiple logistic regression analysis showed that small maximum. Epidermal growth factor receptor tyrosine kinase inhibitors. Epidermal growth factor receptor egfr mutation represents a good response to egfrtyrosine kinase inhibitor and an advantageous prognostic factor in advancedstage nonsmall cell lung cancer nsclc. The mutation in one sample was 2183ag in exon 18, leading to substitution of a glutamine by leucine acid gln849leu. Research article open access epidermal growth factor.
Plasma epidermal growth factor receptor mutation analysis. Table 22 epidermal growth factor receptor mutation test costs based results. Research article open access epidermal growth factor receptor. The aim of the present study was to investigate the mutation rate of the epidermal growth factor receptor egfr in nonsmall cell lung cancer nsclc patients and to apply logistic regression analysis to. Intratumoral heterogeneity is a key factor in the poor therapeutic success for gbm. Epidermal growth factor receptor egfr mutation analysis, gene. Epidermal growth factor receptor mutation testing in thailand. Epidermal growth factor receptor tyrosine kinase nihr journals. Methods we performed a metaanalysis of 17 studies 518 cases assessing. Cggene20 epidermal growth factor receptor egfr testing. The exon 19 and 21 in epidermal growth factor receptor egfr mutation are the. Background randomized phase iii trials have established the efficacy of epidermal growth factor receptor egfr tyrosine kinase inhibitors as firstline treatment for egfr mutationpositive advanced. Mutations of the epidermal growth factor receptor egfr gene in nonsmallcell. However, obtaining tumor tissue for mutation analysis is challenging.
Mutational analysis of egfr tk domain exons from 18 to 21 and. Epidermal growth factor receptor egfr mutation analysis. This study used highly sensitive methods to detect t790m before and after tki therapy and investigated the association of t790m and its mutation. Detection of epidermal growth factor receptor and human epidermal growth factor receptor 2 activating mutations in lung adenocarcimona by highresolution meltiong amplicon analysis. This positioning allows the receptor to attach bind to other proteins, called ligands, outside the cell and to receive signals that help the cell respond to its environment.
Epidermal growth factor receptor egfr mutations, especially deletional mutations in exon 19 del and l858r, predict gefitinib sensitivity in patients with nonsmall cell lung. Epidermal growth factor receptor egfr mutation analysis is a standard approach for initial therapeutic decision in patients with metastatic adenocarcinoma of the lung mal. Objectives epidermal growth factor receptor egfr gene mutations in tumors predict tumor response to egfr tyrosine kinase inhibitors egfrtkis in nonsmallcell lung cancer nsclc. Global epidermal growth factor receptor inhibitors market is rising gradually with a healthy cagr of 9. Sep 21, 2016 purpose most cases of nonsmallcell lung cancer nsclc with dramatic responses to gefitinib have specific activating mutations in the epidermal growth factor receptor egfr, but the predictive value of these mutations has not been defined in large clinical trials. The statistical analysis was carried out using sas software version 9. In this study, we evaluated the epidermal growth factor receptor egfr mutation status of samples of lung cancer patients stored before introduction of the plasma egfr test at our institution. Here, we aimed to detect serum peptidesproteins associated with egfr gene mutation status, and test whether a classification algorithm based. Sometimes, mutations changes in the egfr gene cause epidermal growth factor receptor proteins to be made in higher than normal amounts on some types of cancer cells.
We conducted this study to verify the feasibility of egfr mutation analysis in cytological specimens and investigate the responsiveness to gefitinib treatment in patients carrying egfr. B family of receptors and is composed of an extracellular binding domain, a transmembrane segment and an intracellular tyrosine kinase domain. Epidermal growth factor receptor egfr is a transmembrane protein that functions as a receptor for members of the epidermal growth factor family, the overexpression of which plays a critical role in cellular proliferation, inhibition of apoptosis, angiogenesis, metastasis, and chemoradiotherapy resistance. Epidermal growth factor egf is a protein that stimulates cell growth and differentiation by binding to its receptor, egfr. In this study, we evaluated the epidermal growth factor receptor egfr. Egfr erbb1, her2neu erbb2, her 3 erbb3 and her 4 erbb4. However, egfr exon 20 insertion mutations 10% of all egfr mutations are generally associated with insensitivity to available tkis gefitinib, erlotinib, and. Epidermal growth factor receptor mutation testing in the care of lung cancer patients. B, images are segmented and graylevel texture analyses are. Advanced nonsmallcell lung cancer nsclc is the leading cause of cancerrelated deaths in the world. We show that two commonly occurring epidermal growth factor receptor egfr somatic mutations, l858r and an inframe deletion mutant, del746750, exhibit distinct enzymatic properties relative to wildtype egfr and are differentially sensitive to erlotinib. Rapid detection of epidermal growth factor receptor.
Establishment of a novel method for screening epidermal growth factor receptor tyrosine kinase inhibitor resistance mutations in lung cancer. Jan 25, 2011 activating mutations of the epidermal growth factor receptor egfr confer sensitivity to the tyrosine kinase inhibitors tki, gefitinib and erlotinib. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non. However, the predictive value of egfr mutation for prognosis in nsclc patients after complete surgery, which more reflective of.
This positioning allows the receptor to attach bind to other proteins, called ligands. Erbb2 has no known direct activating ligand, and may be in an activated state constitutively or become active upon heterodimerization with other family members such as egfr. All statistical analyses were performed using sas software version 9. Structural, biochemical, and clinical characterization of. Epidermal growth factor receptor mutation as a risk factor for. In a clinical setting, one component of precision medicine is the detection of cancerspecific mutations using archived samples. However, less than half of patients have adequate tumor samples for mutation analysis. Egfr a gene on chromosome 7p12 that encodes epidermal growth factor, a transmembrane. Epidermal growth factor receptor egfr mutation is the key predictor of egfr tyrosine kinase inhibitors tkis efficacy in nonsmall cell lung cancer nsclc.
1312 771 1310 1096 1565 977 1354 963 1310 392 1346 35 183 563 867 256 1303 626 495 745 352 584 1590 1587 1489 654 208 1236 8 544 639 569 753 1353 527 1412 423 673