Epidermal Growth Factor Receptor Gene and Protein and Gefitinib Sensitivity in Non–Small-Cell Lung Cancer
| Autor: | Elisa Rossi, Elisabetta Magrini, Wilbur A. Franklin, Giovanni Luca Ceresoli, I. Domenichini, Samir E. Witta, Kathleen D. Danenberg, Fred R. Hirsch, Maurizio Tonato, Lucio Crinò, Vanesa Gregorc, Vienna Ludovini, Angelo Sidoni, Marileila Varella-Garcia, Stefania Bartolini, Federico Cappuzzo, Jerry Haney, Lynne T. Bemis, Claudio Doglioni, Paul A. Bunn |
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| Přispěvatelé: | Cappuzzo, F, Hirsch, Fr, Rossi, E, Bartolini, S, Ceresoli, Gl, Bemis, L, Haney, J, Witta, S, Danenberg, K, Domenichini, I, Ludovini, V, Magrini, E, Gregorc, V, Doglioni, Claudio, Sidoni, A, Tonato, M, Franklin, Wa, Crino, L, Bunn, Pa, Varella Garcia, M. |
| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Lung Neoplasms Antineoplastic Agents Protein Serine-Threonine Kinases Disease-Free Survival Gene Expression Regulation Enzymologic Gefitinib Predictive Value of Tests Epidermal growth factor Carcinoma Non-Small-Cell Lung Proto-Oncogene Proteins Internal medicine Biomarkers Tumor medicine Humans EGFR Gene Amplification Epidermal growth factor receptor Lung cancer Protein Kinase Inhibitors EGFR Protein Overexpression In Situ Hybridization Fluorescence Survival analysis Aged Proportional Hazards Models biology Reverse Transcriptase Polymerase Chain Reaction Hazard ratio Sequence Analysis DNA Middle Aged medicine.disease Immunohistochemistry Survival Analysis ErbB Receptors Gene Expression Regulation Neoplastic Endocrinology Research Design Multivariate Analysis Quinazolines biology.protein Female Proto-Oncogene Proteins c-akt medicine.drug |
| Zdroj: | JNCI: Journal of the National Cancer Institute. 97:643-655 |
| ISSN: | 1460-2105 0027-8874 |
| Popis: | Background: Gefitinib is a selective inhibitor of the epidermal growth factor (EGFR) tyrosine kinase, which is overexpressed in many cancers, including non-small-cell lung cancer (NSCLC). We carried out a clinical study to compare the relationship between EGFR gene copy number, EGFR protein expression, EGFR mutations, and Akt activation status as predictive markers for gefitinib therapy in advanced NSCLC. Methods: Tumors from 102 NSCLC patients treated daily with 250 mg of gefitinib were evaluated for EGFR status by fluorescence in situ hybridization (FISH), DNA sequencing, and immunohistochemistry and for Akt activation status (phospho-Akt [P-Akt]) by immunohistochemistry. Time to progression, overall survival, and 95% confidence intervals (CIs) were calculated and evaluated by the Kaplan-Meier method; groups were compared using the log-rank test. Risk factors associated with survival were evaluated using Cox proportional hazards regression modeling and multivariable analysis. All statistical tests were two-sided. Results: Amplification or high polysomy of the EGFR gene (seen in 33 of 102 patients) and high protein expression (seen in 58 of 98 patients) were statistically significantly associated with better response (36% versus 3%, mean difference = 34%, 95% CI = 16.6 to 50.3; P |
| Databáze: | OpenAIRE |
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