Turkish Journal of Pathology

Türk Patoloji Dergisi

Turkish Journal of Pathology

Turkish Journal of Pathology

2010, Vol 26, Num, 3     (Pages: 222-229)

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 PALA 1, Osman ZEKİOĞLU 1, Necmettin ÖZDEMİR 1, Rasih YILMAZ 2, Murat KAPKAÇ 2

1 Department of Pathology, Ege University, Faculty of Medicine, İZMİR, TURKEY
2 Department of General Surgery, Ege University, Faculty of Medicine, İZMİR, TURKEY

DOI: 10.5146/tjpath.2010.01028
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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.

Keywords : Breast cancer, Genes, HER2/neu, DNA topoisomerase IIalpha Immunohistochemistry, Fluorescence in situ hybridization