Assessment of the concordance between fluorescence in-situ hybridization and immunohistochemistry in evaluating topoisomerase IIα in breast carcinoma

Abstract

Background Topoisomerase IIα (TOP2A), encoded by TOP2A gene, is a molecular target for anthracycline therapy; hence, it can serve as a predictive or prognostic factor. There are several techniques used for measuring TOP2A status. The relative value of TOP2A gene amplification evaluated by fluorescence in-situ hybridization (FISH) and protein expression analyzed by immunohistochemistry (IHC) is yet unclear in the literature. Aim To evaluate the concordance between FISH and IHC for TOP2A status and to assess their relations with some prognostic clinicopathological parameters. Materials and methods A total of 86 invasive breast cancer paraffin blocks were retrieved from the archives of Pathology Department, National Cancer Institute, Cairo University, and were subjected to IHC, with a cutoff value of 10%, and FISH analysis with TOP2A/centromere enumeration probe 17 ratio of at least two for TOP2A expressions. The concordance between the results of both techniques as well as relations with selected prognostic parameters was evaluated. Results Of 86 invasive breast carcinomas, 43 (50%) revealed TOP2A protein overexpression, whereas 23 (26.7%) cases had TOP2A gene amplification. TOP2A gene amplification was recognized in 16 of 43 TOP2A protein-expressed cases, with 37.2% concordance rate and 0.209 κ statistics. TOP2A gene amplification was significantly correlated with human epidermal growth factor receptor-2 immuno-expressing tumors and with molecular subtypes (P Conclusion Discordance was evident between TOP2A gene amplification and protein expression. However, TOP2A gene amplification has a valuable prognostic influence, whereas protein expression is still a predictive factor useful to guide chemotherapy.