Herceptin Research Today is a free monthly online journal that collates and summarizes the latest research about Herceptin, including details on side-effects, breast cancer, treatment, therapy. | ||||||||
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A modified approach for I-FISH evaluation of ERBB2 (HER-2) gene copy numbers in breast carcinomas: comparison with HER-2/CEP17 ratio system.Mrhalova M, Kodet R Department of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University in Prague, V Uvalu 84, Prague 5, 150 06, Czech Republic. marcela.mrhalova@lfmotol.cuni.cz PURPOSE: The evaluation of ERBB2 gene copy numbers and ERBB-2 protein expression in invasive duct carcinomas of the mammary gland (IDC) has been introduced as a part of a regular investigation protocol. Amplification of the ERBB2 gene detected by fluorescence in situ hybridization on interphasic nuclei (I-FISH) is used as a criterion for Herceptin administration. To improve characterization of cases with a borderline ERBB2 gene amplification, we applied a modified evaluation of the ERBB2 gene copy numbers. The results were compared with a commonly used HER-2/CEP17 ratio calculation. METHODS: We investigated 175 patients with primary IDCs in histological sections from paraffin embedded tissue with PathVysion HER-2 DNA Probe Kit (Vysis). Tumor cells of each case were sorted according to the number of ERBB2 signals into groups of tumor cells without amplification, with moderate amplification (< or =10 signals) and with strong amplification (>10 signals). If >10% of tumor cells had moderate or strong amplification of the ERBB2 gene, the case was reported as "moderately" or "strongly" amplified. RESULTS: The groups of patients classified by the proposed system as "without" and as with "strong" amplification had the HER-2/CEP17 ratio <1.91 (median 1.22, n = 33) and >2.3 (median 6.85, n = 115), respectively. Thus, the findings using the two systems of evaluation yielded similar results for these groups of patients. In cases, classified as with "moderate" amplification, the HER-2/CEP17 ratio varied from 1.3 to 4.77 (median 2.11, n = 27). Twelve of these 27 patients were according to the HER-2/CEP17 ratio system "not amplified" (1.3-1.93, median 1.72). Median percentage of the tumor cells with amplification of the ERBB2 gene was 14.5% in this subgroup. Of these 12 cases, 10 were ERBB-2 protein positive, and would be candidates for Herceptin therapy. CONCLUSION: The criteria for evaluation of the ERBB2 gene copy number proposed for this study separate gray zone cases with a borderline HER-2/CEP17 finding. The proposed system is easy to apply and characterizes a heterogeneity of the ERBB2 gene copy number in IDC tumor cell population more precisely than the currently used HER-2/CEP17 ratio system. Published 29 March 2007 in J Cancer Res Clin Oncol, 133(5): 321-9.
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