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2010, Volume 26, Number 3, Page(s) 222-229     
[ Abstract (Turkish) ] [ PDF ] [ Similar Articles ]
DOI: 10.5146/tjpath.2010.01028
Comparison of Immunohistochemistry and Fluorescence In Situ Hybridization for the Analysis of HER2/neu and Topoisomerase II-alpha Status in Human Breast Cancer
Emel Ebru PALA1, Osman ZEKİOĞLU1, Necmettin ÖZDEMİR1, Rasih YILMAZ2, Murat KAPKAÇ2
1Department of Pathology, Ege University, Faculty of Medicine, İZMİR, TURKEY
2Department of General Surgery, Ege University, Faculty of Medicine, İZMİR, TURKEY
Keywords: Breast cancer, Genes, HER2/neu, DNA topoisomerase IIalpha Immunohistochemistry, Fluorescence in situ hybridization

Objective: HER2/neu is overexpressed/amplified in 20% of breast cancers. HER2/neu status plays a role in determining the patients who might benefit from hormonal therapy and targeted therapy with Trastuzumab. The main cause of HER2/neu overexpression is gene amplification. 10-25% of patients show Topoisomerase II-alpha gene alterations with HER2/neu amplification. The objective of this study was to compare and standardize immunohistochemical and fluorescence in situ hybridization methods for the analysis of HER2/ neu and Topoisomerase II-alpha.

Material and Method: 78 cases with invasive breast cancer were selected from the archives. Anti-human HER2/neu, and Topoisomerase II-alpha antibodies were used to determine protein expression levels by immunohistochemistry; TOP2A/HER2/CEP17 probe set was used to examine genomic alterations by fluorescence in situ hybridization.

Result: HER2/neu overexpression was observed in 59% and HER2/ neu amplification in 44.9% of the cases. The mean percentage of tumor cells that expressed Topoisomerase II-alpha was 25.9%. 12 cases with Topoisomerase II-alpha amplification (15.4%) also amplified with HER2/neu. The association between HER2/neu and Topoisomerase II-alpha amplification and their expression levels was statistically significant (p<0.01, p=0.005). The concordance between immunohistochemistry and fluorescence in situ hybridization was 71.7% in 3+ and 11.7% in 2+ cases. Two patients showed chromosome 17 polysomy.

Conclusion: The concordance between immunohistochemistry and fluorescence in situ hybridization was low in 3+ and 2+ cases. Immunohistochemistry and fluorescence in situ hybridization should be performed together until the standardization of the whole process that affects immunohistochemistry and fluorescence in situ hybridization results. If Topoisomerase II-alpha gene alterations are proven by clinical studies to affect the tumor response to the anthracyclines, it will be appropriate to detect these alterations by fluorescence in situ hybridization.


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