Assessment of Topoisomerase II alpha Status in Breast Cancer by Quantitative PCR, Gene Expression Microarrays, Immunohistochemistry, and Fluorescence in Situ Hybridization

作者：Romero Atocha; Martin Miguel; Cheang Maggie C U; Lopez Garcia Asenjo Jose Antonio; Oliva Belen; He Xiaping; de la Hoya Miguel; Garcia Saenz Jose Angel; Arroyo Fernandez Manuel; Diaz Rubio Eduardo; Perou Charles M; Caldes Llopis Trinidad

来源：American Journal Of Pathology, 2011, 178(4): 1453-1460.

DOI：10.1016/j.ajpath.2010.12.042

Anthracyclines are frequently used for the treatment of breast cancer and topoisomerase II alpha (TOP2A) is considered to be the molecular Orget. 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. (Am J Pathol 2011, 178:1453-1460; DOI: 10.1016/j.ajpath.2010.12.042)

• 出版日期2011-4