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Review
. 2011 Apr;178(4):1453-60.
doi: 10.1016/j.ajpath.2010.12.042.

Assessment of Topoisomerase II α status in breast cancer by quantitative PCR, gene expression microarrays, immunohistochemistry, and fluorescence in situ hybridization

Atocha Romero  1 , Miguel Martín, Maggie C U Cheang, José Antonio López García-Asenjo, Belén Oliva, Xiaping He, Miguel de la Hoya, Jose Ángel García Sáenz, Manuel Arroyo Fernández, Eduardo Díaz Rubio, Charles M Perou, Trinidad Caldés Llopis
Affiliations
Review

Assessment of Topoisomerase II α status in breast cancer by quantitative PCR, gene expression microarrays, immunohistochemistry, and fluorescence in situ hybridization

Atocha Romero et al. Am J Pathol. 2011 Apr.

Abstract

Anthracyclines are frequently used for the treatment of breast cancer and topoisomerase II alpha (TOP2A) is considered to be the molecular target. Numerous studies have evaluated the predictive value of TOP2A using different methodological approaches and inconsistent results have been reported. Indeed, the correlation between techniques for the assessment of TOP2A status has not been well evaluated. In this study, we determined TOP2A status in 61 breast tumor samples by real-time PCR, DNA microarrays, immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH), and then evaluated these results with clinical-pathological features and breast cancer intrinsic subtypes. First, we observed a statistical significant correlation of TOP2A gene expression between real-time PCR and microarrays (Pearson coefficient, 0.816; P < 0.001), and both predicted TOP2A IHC results fairly well (area under the curve > 0.74). In contrast, poor agreement between FISH and IHC data was observed (k: 0.134). Secondly, TOP2A expression was found significantly associated with cell proliferation, and with the highly proliferative Luminal B, Her2-enriched and Basal-like intrinsic subtypes. In conclusion, TOP2A expression in breast cancer was associated with high proliferation and aggressive tumor subtypes and appears to be independent of its amplification status. All of these features should be taken into consideration when assessing the predictive value of TOP2A for anthracycline-based chemotherapy.

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Figures

Figure 1
Figure 1
A: Box plot. The TOP2A mRNA expression values, measured by gene expression microarrays, according to genomic subtype. B: Box plot. The TOP2A mRNA expression values, measured by Q-PCR, according to genomic subtype. C: Bar chart. The number of TOP2A-positive (POS) and TOP2A-negative (NEG) tumors, according to IHC, for each subtype. D: Bar chart. The number of TOP2A-positive and TOP2A-negative tumors, according to FISH, for each subtype. CNA indicates copy number alteration.
Figure 2
Figure 2
Correlation between TOP2A expression values, assessed by gene expression microarrays and Q-PCR.
Figure 3
Figure 3
Receiver operating characteristic curves. Prediction of TOP2A IHC positivity according to gene expression microarrays and Q-PCR data.
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References

    1. Ryberg M., Nielsen D., Cortese G., Nielsen G., Skovsgaard T., Andersen P. New insight into epirubicin cardiac toxicity: competing risks analysis of 1097 breast cancer patients. J Natl Cancer Inst. 2008;100:1058–1067. - PubMed
    1. Diamandidou E., Buzdar A.U., Smith T.L., Frye D., Witjaksono M., Hortobagyi G.N. Treatment-related leukemia in breast cancer patients treated with fluorouracil-doxorubicin-cyclophosphamide combination adjuvant chemotherapy: the University of Texas M.D.: Anderson Cancer Center experience. J Clin Oncol. 1996;14:2722–2723. - PubMed
    1. Tewey K.M., Rowe T.C., Yang L., Halligan B.D., Liu L.F. Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science. 1984;226:466–468. - PubMed
    1. Minotti G., Menna P., Salvatorelli E., Cairo G., Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004;56:185–229. - PubMed
    1. Osheroff N. Biochemical basis for the interaction of type I and type II topoisomerases with DNA. Pharmacol Ther. 1989;41:233–241. - PubMed

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