Increased HER2 gene copy number is associated with response to gefitinib therapy in epidermal growth factor receptor-positive non-small-cell lung cancer patients
Autor: | Adi F. Gazdar, Elisa Rossi, Paul A. Bunn, Giovanni Luca Ceresoli, Luca Toschi, Federico Cappuzzo, Stefania Bartolini, Hisayuki Shigematsu, I. Domenichini, Wilbur A. Franklin, L. Crinò, M. Varella-Garcia, Fred R. Hirsch, Vanesa Gregorc, Vienna Ludovini |
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Rok vydání: | 2005 |
Předmět: |
Cancer Research
medicine.medical_specialty Lung Neoplasms DNA Mutational Analysis Gene Dosage Antineoplastic Agents Gene dosage Cohort Studies Gefitinib Growth factor receptor Internal medicine Carcinoma Non-Small-Cell Lung medicine Humans Copy-number variation Epidermal growth factor receptor Lung cancer In Situ Hybridization Fluorescence Polysomy biology business.industry Gene Expression Profiling Genes erbB-2 medicine.disease Survival Analysis ErbB Receptors Endocrinology Treatment Outcome Oncology Cancer research biology.protein Quinazolines business Tyrosine kinase medicine.drug |
Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 23(22) |
ISSN: | 0732-183X |
Popis: | PurposeIn non-small-cell lung cancer (NSCLC), response to tyrosine kinase inhibitors (TKIs) is significantly associated with the presence of increased copy number and/or activating mutations of the epidermal growth factor receptor gene (EGFR). Preclinical data indicate that HER2, a member of the EGFR family, could enhance TKI sensitivity.Patients and MethodsHER2 gene copy numbers per cell were evaluated by fluorescent in situ hybridization (FISH) in 102 NSCLC patients treated with gefitinib, and previously evaluated for EGFR status by FISH, immunohistochemistry, and presence of mutations.ResultsPatients with HER2 high copy number (high polysomy and gene amplification [HER2 FISH positive]) represented 22.8% of patients, and compared with patients with no or low gain (HER2 FISH negative), had significantly better objective response (OR, 34.8% v 6.4%; P = .001), disease control rate (DCR, 56.5% v 33.3%; P = .04), time to progression (TTP, 9.05 v 2.7 months; P = .02), and a trend toward longer overall survival (OS, 20.8 v 8.4 months; P = .056). HER2 protein expression investigated by immunohistochemistry was positive in only five of 72 (7%) patients analyzed and all 89 patients tested by DNA sequencing were negative for mutations in HER2 exon 20. Patients with HER2 FISH-positive tumors displaying increased expression of EGFR protein, gene gain, or mutations (EGFR positive) had a significantly better OR, DCR, TTP, and OS than patients negative for both receptors.ConclusionIncreased copy number of the HER2 gene is associated with gefitinib sensitivity in EGFR-positive patients, supporting use of HER2 FISH analysis for selection of patients for TKI therapy. |
Databáze: | OpenAIRE |
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