title: Assessment of Topoisomerase II α status in breast cancer by quantitative PCR, gene expression microarrays, immunohistochemistry, and fluorescence in situ hybridization.
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.
authors: Department of Medical Oncology, Hospital Clínico San Carlos, Madrid, Spain.
authors: Atocha
authors: A
authors: Romero
authors: Miguel
authors: M
authors: Martín
authors: Maggie C U
authors: MC
authors: Cheang
authors: José Antonio
authors: JA
authors: López García-Asenjo
authors: Belén
authors: B
authors: Oliva
authors: Xiaping
authors: X
authors: He
authors: Miguel
authors: M
authors: de la Hoya
authors: Jose Ángel
authors: JÁ
authors: García Sáenz
authors: Manuel
authors: M
authors: Arroyo Fernández
authors: Eduardo
authors: E
authors: Díaz Rubio
authors: Charles M
authors: CM
authors: Perou
authors: Trinidad
authors: T
authors: Caldés Llopis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics*; D001706:Biopsy; D001943:Breast Neoplasms / Q000201:enzymology*; D049109:Cell Proliferation; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis* / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D000075223:Poly-ADP-Ribose Binding Proteins; D016133:Polymerase Chain Reaction / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C000618811:TOP2A protein, human