PMID- 21435434 OWN - NLM STAT- MEDLINE DCOM- 20110715 LR - 20211020 IS - 1525-2191 (Electronic) IS - 0002-9440 (Print) IS - 0002-9440 (Linking) VI - 178 IP - 4 DP - 2011 Apr TI - Assessment of Topoisomerase II alpha status in breast cancer by quantitative PCR, gene expression microarrays, immunohistochemistry, and fluorescence in situ hybridization. PG - 1453-60 LID - 10.1016/j.ajpath.2010.12.042 [doi] AB - 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. CI - Copyright (c) 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. FAU - Romero, Atocha AU - Romero A AD - Department of Medical Oncology, Hospital Clinico San Carlos, Madrid, Spain. FAU - Martin, Miguel AU - Martin M FAU - Cheang, Maggie C U AU - Cheang MC FAU - Lopez Garcia-Asenjo, Jose Antonio AU - Lopez Garcia-Asenjo JA FAU - Oliva, Belen AU - Oliva B FAU - He, Xiaping AU - He X FAU - de la Hoya, Miguel AU - de la Hoya M FAU - Garcia Saenz, Jose Angel AU - Garcia Saenz JA FAU - Arroyo Fernandez, Manuel AU - Arroyo Fernandez M FAU - Diaz Rubio, Eduardo AU - Diaz Rubio E FAU - Perou, Charles M AU - Perou CM FAU - Caldes Llopis, Trinidad AU - Caldes Llopis T LA - eng GR - P30 ES010126/ES/NIEHS NIH HHS/United States GR - P50 CA058223/CA/NCI NIH HHS/United States PT - Journal Article PT - Review PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Antigens, Neoplasm) RN - 0 (DNA-Binding Proteins) RN - 0 (Poly-ADP-Ribose Binding Proteins) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - EC 5.99.1.3 (DNA Topoisomerases, Type II) RN - EC 5.99.1.3 (TOP2A protein, human) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Antigens, Neoplasm/*biosynthesis/*genetics MH - Biopsy MH - Breast Neoplasms/*enzymology MH - Cell Proliferation MH - DNA Topoisomerases, Type II/*biosynthesis/*genetics MH - DNA-Binding Proteins/*biosynthesis/*genetics MH - Female MH - *Gene Expression Regulation, Enzymologic MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Immunohistochemistry/methods MH - In Situ Hybridization, Fluorescence/methods MH - Middle Aged MH - Oligonucleotide Array Sequence Analysis MH - Poly-ADP-Ribose Binding Proteins MH - Polymerase Chain Reaction/methods MH - Receptor, ErbB-2/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction PMC - PMC3078442 EDAT- 2011/03/26 06:00 MHDA- 2011/07/16 06:00 PMCR- 2012/04/01 CRDT- 2011/03/26 06:00 PHST- 2010/08/09 00:00 [received] PHST- 2010/12/03 00:00 [revised] PHST- 2010/12/23 00:00 [accepted] PHST- 2011/03/26 06:00 [entrez] PHST- 2011/03/26 06:00 [pubmed] PHST- 2011/07/16 06:00 [medline] PHST- 2012/04/01 00:00 [pmc-release] AID - S0002-9440(11)00042-3 [pii] AID - AJPA217 [pii] AID - 10.1016/j.ajpath.2010.12.042 [doi] PST - ppublish SO - Am J Pathol. 2011 Apr;178(4):1453-60. doi: 10.1016/j.ajpath.2010.12.042.