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Growth Factor Receptor Mutations (growth + factor_receptor_mutation)

Distribution by Scientific Domains
Medical Sciences100%

Kinds of Growth Factor Receptor Mutations

  • epidermal growth factor receptor mutation
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    Selected Abstracts

    THE MOLECULAR FUTURE IN CYTOLOGY

    CYTOPATHOLOGY, Issue 2006
    M. Salto-Tellez
    Molecular diagnosis is the application of molecular biology techniques and knowledge of the molecular mechanisms of disease to diagnosis, prognostication and treatment of diseases. Molecular Diagnosis is, arguably, the fastest growing area of diagnostic medicine. The US market for molecular testing generated $1.3 billion in 2000, which was predicted to increase to about $4.2 billion by 2007.1 We proposed the term Diagnostic Molecular Cytopathology to define the application of molecular diagnosis to cytopathology2. Diagnostic Molecular Cytopathology is essential for the following reasons: (i) Molecular testing is sometimes indispensable to establish an unequivocal diagnosis on cell preparations; (ii) Molecular testing provides extra information on the prognosis or therapy of diseases diagnosed by conventional cytology; (iii) Molecular testing provides genetic information on the inherited nature of diseases that can be directly investigated in cytology samples, by either exfoliation or by fine needle aspiration; (iv) Sometimes the cytopathology sample is the most convenient (or the only available) source of material for molecular testing; (v). Direct molecular interrogation of cells allows for a diagnostic correlation that would otherwise not be possible. Parallel to this direct diagnostic implication, cytopathology is increasing important in the validation of biomarkers for specific diseases, and in therefore of significant importance in the overall translational research strategies. We illustrate its application in some of the main areas of oncology molecular testing, such as molecular fingerprinting of neoplasms,3 lymphoreticular diseases,2 sarcomas4 and lung cancer,5 as well as translational research using diagnostic cytopathology techniques. The next years will see the consolidation of Diagnostic Molecular Cytopathology, a process that will lead to a change of many paradigms. In general, diagnostic pathology departments will have to reorganize molecular testing to pursue a cost-efficient operation. Sample preparation will have to take into account optimal preservation of nuclear acids. The training of technical staff and the level of laboratory quality control and quality assurance would have to follow strict clinical (not research) laboratory parameters. And, most importantly, those pathologists undertaking molecular diagnosis as a discipline would have to develop their professional expertise within the same framework of fellowships and professional credentials that is offered in other sub-specialties. The price to pay if this effort is not undertaken is too important for the future of diagnostic pathology in general. The increasing characterization of molecular biomarkers with diagnostic, prognostic or therapeutic value is making the analysis of tissue and cell samples prior to treatment a more complex exercise. If cytopathologists and histopathologists allow others to take charge of molecular diagnosis, our overall contribution to the diagnostic process will be diminished. We may not become less important, but we may become less relevant. However, those within the discipline of diagnostic pathology who can combine the clinical background of diseases with the morphological, immunocytochemical and molecular diagnostic interpretation will represent bona fide diagnostic specialists. Such ,molecular cytopathologists' would place themselves at the centre of clinical decision-making. Reference:, 1. Liz Fletcher. Roche leads molecular diagnostics charge. Nature Biotechnol 20, 6,7; 2002 2. Salto-Tellez M and Koay ESC. Molecular Diagnostic Cytopathology - Definitions, Scope and Clinical Utility. Cytopathology 2004; 15:252,255 3. Salto-Tellez M, Zhang D, Chiu LL, Wang SC, Nilsson B, and Koay ESC. Immunocytochemistry Versus Molecular Fingerprinting of Metastases. Cytopathology, 2003 Aug; 14(4):186,90. 4. Chiu LL, Koay SCE, Chan NL and Salto-Tellez M. Molecular Cytopathology: Sequencing of the EWS-WT1 Gene Fusion Transcript in the Peritoneal Effusion of a Patient with Desmoplastic Small Round Cell Tumour. Diagnostic Cytopathology, 2003 Dec; 29(6): 341,3. 5. TM Chin, D Anuar, R Soo, M Salto-Tellez, WQ Li, B Ahmad, SC Lee, BC Goh, K Kawakami, A Segal, B Iacopetta, R Soong. Sensitive and Cost-Effective deptection of epidermal growth factor Receptor Mutations in Small Biopsies by denaturing High Performance Liquid Chromatography. (In press). [source]

    Epidermal growth factor receptor mutation, but not sex and smoking, is independently associated with favorable prognosis of gefitinib-treated patients with lung adenocarcinoma

    CANCER SCIENCE, Issue 2 2008
    Shinichi Toyooka
    Epidermal growth factor receptor (EGFR) mutations have been reported as a predictive factor for favorable prognosis of gefitinib-treated patients with lung adenocarcinoma. However, its confounding with sex and smoking makes it unclear whether the EGFR mutation is independently associated with prolonged patient survival. In this study, we analyzed a large-scale database to discriminate the survival impact of EGFR mutations against those of sex and smoking after gefitinib therapy. EGFR mutations in exon19 and exon21 named drug-sensitive EGFR mutations were examined to investigate the impact of EGFR mutation, sex, and smoking status on survival of 362 gefitinib-treated patients with lung adenocarcinoma. Drug-sensitive EGFR mutations were detected in 169 patients (46.7%). The multivariate analysis including EGFR, sex, and smoking status showed that drug-sensitive EGFR mutations were significantly related to longer overall survival (OS) (P < 0.001) and progression-free survival (PFS) (P < 0.001). In addition, we investigated the impact of sex and smoking status according to EGFR mutation status, and the impact of EGFR mutation status according to sex and smoking status on survival. Sex and smoking status were not significantly associated with longer OS and PFS according to EGFR mutation status. Drug-sensitive EGFR mutations were significantly associated with longer OS and PFS according to sex or smoking status. Our results indicated that drug-sensitive EGFR mutations were the only independent factor for longer survival of patients treated with gefitinib, suggesting that patient selection based on EGFR mutation status for gefitinib therapy will lead to a better outcome for patients with lung adenocarcinoma. (Cancer Sci 2008; 99: 303,308) [source]

    Association of epidermal growth factor receptor mutations in lung cancer with chemosensitivity to gefitinib in isolated cancer cells from Japanese patients

    EUROPEAN JOURNAL OF CANCER CARE, Issue 3 2007
    K. NAKATANI md, assistant professor
    Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are reported to be associated with clinical responsiveness of lung cancer to gefitinib, an EGFR tyrosine kinase inhibitor. To elucidate the association between somatic mutations and the pharmacological actions of gefitinib, the chemosensitivity of isolated cancer cells from the lungs of Japanese patients to gefitinib was examined by the collagen gel-droplet embedded culture drug sensitivity test in vitro. In 30 specimens isolated from non-small-cell lung cancer patients, mutations were observed in eight tumour specimens (27%) and chemosensitivity to gefitinib was observed in seven specimens (23%). However, somatic mutations were not predominantly associated with chemosensitivity to gefitinib in vitro. Both mutation and chemosensitivity frequencies in this study were higher than those reported in studies from the United States, indicating a possible ethnic difference. Moreover, both frequencies were much higher in females than in males. Since a gender difference in chemosensitivity to gefitinib was observed in isolated cancer cells in vitro, this suggests that gefitinib works in part through the suppression of EGFR signalling, but that other factors, including sex-related factors, may participate in gefitinib action. [source]

    Epidermal growth factor receptor mutations in needle biopsy/aspiration samples predict response to gefitinib therapy and survival of patients with advanced nonsmall cell lung cancer

    INTERNATIONAL JOURNAL OF CANCER, Issue 4 2006
    Jin-Yuan Shih
    Abstract Recently, mutations in the epidermal growth factor receptor (EGFR) gene in nonsmall cell lung cancer (NSCLC) patients were reported to correlate with gefitinib response. Less than 30% of NSCLC patients are surgically resectable; however, molecular analysis has to rely on nonsurgical diagnostic tissue samples. The objective of this study is to investigate EGFR mutation analysis on needle biopsy/aspiration samples and its correlations with gefitinib response and patients' survival. EGFR mutation was assessed from DNA of 63 paraffin-embedded small needle biopsy/aspiration specimens from 62 patients with NSCLC treated with gefitinib. The peripheral blood lymphocyte DNA of the patients was sequenced to verify the EGFR mutation. EGFR mutations were found in 47% of 62 patients (60% of 20 CT-guided biopsies, 44% of 18 ultrasound-guided biopsies, 31% of 16 endoscopic biopsies and 44% of 9 effusion cell blocks). EGFR mutations were frequently present in females (p = 0.006) and never smokers (p = 0.04). Patients with EGFR mutations had a significantly better response rate compared to that of the nonmutation group (p < 0.001). Multivariate analysis showed that EGFR mutation (p < 0.001) and PS 0,1 (p = 0.02) were independently associated with a better response rate. Cox regression analysis showed that EGFR mutation was the independent prognostic factor for progression-free survival (p = 0.008) and overall survival (p = 0.03). In conclusion, EGFR mutation analysis is feasible in needle biopsy/aspiration paraffin-fixed specimens. EGFR mutation is an independent predictor of gefitinib response and survival in patients of advanced NSCLC treated by gefitinib. © 2005 Wiley-Liss, Inc. [source]

    Serum carcinoembryonic antigen level is associated with epidermal growth factor receptor mutations in recurrent lung adenocarcinomas

    CANCER, Issue 12 2007
    Fumihiro Shoji MD
    Abstract BACKGROUND. The presence of epidermal growth factor receptor (EGFR) gene mutations is a good indicator of the clinical efficacy of gefitinib in patients with nonsmall cell lung cancer. It was recently reported that the serum carcinoembryonic antigen (CEA) level could be a predictive factor for the efficacy of gefitinib treatment; therefore, it is suggested that the EGFR gene mutation is associated with the serum CEA level. The current study analyzed the association between EGFR gene mutations and clinical features, including the serum CEA level, in patients with recurrent lung adenocarcinomas. METHODS. A total of 48 lung adenocarcinoma patients with postoperative disease recurrence who underwent chemotherapy were investigated. EGFR gene mutations at exons 18, 19, and 21 were measured using surgical specimens taken from the primary tumor. RESULTS. Mutations of the EGFR gene were detected in 25 of the 48 patients and the abnormal serum CEA concentration at the time of disease recurrence was found to be significantly associated with the incidence of EGFR gene mutations (P = .045). The rate of EGFR gene mutations significantly increased as the serum CEA level increased (serum CEA level; <5 vs ,5 <20 vs ,20 = 35% vs 55% vs 87.5%, respectively, P = .040). A multivariate analysis revealed that a higher serum CEA level at the time of disease recurrence is independently associated with EGFR gene mutations (P = .036) with an odds ratio of 4.70 (95% confidence interval, 1.1,21.1). CONCLUSIONS. The serum CEA level appears to be closely associated with the presence of EGFR gene mutations in patients with pulmonary adenocarcinomas. Cancer 2007. © 2007 American Cancer Society. [source]

    Soy consumption reduces the risk of non-small-cell lung cancers with epidermal growth factor receptor mutations among Japanese

    CANCER SCIENCE, Issue 6 2008
    Keitaro Matsuo
    Epidermal growth factor receptor (EGFR) mutations play substantial roles in genesis and proliferation of non-small-cell lung cancers (NSCLCs). We recently found that reproductive factors have a substantial impact on risk of development of NSCLCs featuring such EGFR mutations. Therefore, we explored the influence of dietary habits on NSCLC risk with reference to the EGFR mutational status. We conducted a case-control study using 353 patients with NSCLCs (122 EGFR mutated and 231 EGFR wild-type) and 1765 age-sex matched non-cancer control subjects. Dietary exposure was based on a semiquantitative food frequency questionnaire and impact of major food items, like meats, seafoods, vegetables and soybean products was assessed by multivariate logistic regression. Soybean products demonstrated a protective association with EGFR mutated, but not EGFR wild-type NSCLCs, with multivariate-adjusted odds ratios and 95% confidence intervals for the 2nd and 3rd tertile of soybean product consumption of 0.79 (0.50,1.27) and 0.56 (0.34,0.93) relative to those in the lowest tertile (trend P = 0.023). In conclusion, soy consumption may exert a protective association against the development of NSCLCs with EGFR mutations, providing possible insights into mechanisms of their genesis. (Cancer Sci 2008; 99: 1202,1208) [source]