Immunohistochemical her-2/ neu expression with gene amplification by fluorescence insitu hybridization for assessment in breast carcinomas

Objective: To compare gene amplification of HER-2/neu gene by fluorescence in situ hybridization (FISH) in moderate to strong immunohistochemically (IHS) positive HER-2/new cases of invasive breast carcinomas. Study Design: Cross- sectional study. Place and Duration of Study: Section of Histopathology, The Aga Khan University Hospital, Karachi, from January 2004 to December 2006. Patients and Methods: Forty one (41) diagnosed cases of invasive breast carcinomas were included in this study in which already determined immunohistochemical HER-2/neu expression was scored as either 2+ or 3+, based on the intensity of membranous staining. These cases were further evaluated for gene amplification by FISH. For gene amplification, a ratio of HER-2/CEP > 2 was accepted as positive gene amplification. Results: Out of a total 41 cases, which were scored as 2+ and 3+ by IHC, 14 cases (34.1%; 95% confidence interval: 19%-49.3% ) showed gene amplification by FISH. Proportion of FISH positivity in IHC 2+ cases alone was found to be 25% (95% confidence interval: 10.5%-41%). In contrast, a majority of IHC 3+ cases (5 of 6) were positive by FISH studies. Conclusion: IHC is appropriate for initial HER-2/neu assessment and patients with tumors scored as 3+ may be treated alone based on this information provided strict quality control and 95% concordance with FISH assays; however, patients with tumors interpreted as 2+, would benefit from gene amplification by FISH studies for more accurate assessment to avoid inaccurate prognostication and treatment.