Immunohistochemical her-2/ Neu expression with gene amplification by fluorescence in situ hybridization for...

To compare gene amplification of HER-2/neu gene by fluorescence in situ hybridization (FISH) in moderate to strong immunohistochemically (IHS) positive HER-2/neu cases of invasive breast carcinomas.

Cross- sectional study.

Section of Histopathology, The Aga Khan University Hospital, Karachi, from January 2004 to December 2006.

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 Z 2 was accepted as positive gene amplification.

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.

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.