Abstract PD02-06: Concordance between immunohistochemistry and FISH(fluorescence in sity hybridization) & SISH(silver in situ hybridization) for assessment of the HER2

Goals: Accurate assessment of the human epidermal growth factor receptor 2 (HER2) of invasive breast cancer with Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) & Silver in situ hybridization(SISH) is very important to decide treatment of targeted therapy with the humanized monoclonal antibody trastuzumab and the dual tyrosine kinase inhibitor lapatinib. The accuracy of these three testing methods can be adversely affected by various factors. We performed a retrospective analysis of the concordance of IHC and FISH & SISH analysis for HER2/neu at Donga-A Medical Center and reviewed possible causes of disparity between these two methods. Methods: We performed retrospective review of a total of 416 invasive ductal carcinomas evaluated for HER2/neu at the Department of Surgery in Dong-A Medical Center between 2005 and 2011. We reviewed this data retrospectively and evaluated the concordance between IHC and FISH & SISH. Results: Comparison of the routinely assessed immunohistochemical HER2 status and FISH & SISH revealed that ten invasive carcinomas diagnosed immunohistochemically as highly overexpressed (score 3+) did not show amplification of the HER2 gene by FISH n that these are false positives (SISH: false positive: 7 cases). Eight invasive carcinomas diagnosed immunohistochemically as Negatively expressed (score 0) showed amplification of the HER2 gene by SISH on that these are false negative. Fourteen tumor, which scored as 2+ by IHC, was proven to be amplified on initial testing with FISH (SISH: 6 cases). Concordance between IHC and FISH analysis was good (171/181= 94.5%) (false positive: 5.5%) (SISH: 228/235=97.0%, false positive 3.4%, false negative 2.9%) and within the published range. Conclusion: IHC as first-line testing for HER2 may result in false positive and false negative results. The novel ASCO/CAP criteria for the immunohistochemical evaluation of the HER2 status may prevent some false positive results. The discordant cases between IHC and FISH & SISH represent a well-recognized subset of genetic heterogeneity in HER2/neu, which is known to contribute to positive IHC and negative FISH & SISH tests. The most powerful method for studying HER2 status is ISH. However, in heterogeneous carcinomas even FISH may not succeed in a correct evaluation of HER2. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD02-06.