title: Prognostic significance of TOP2A gene dosage in HER-2-negative breast cancer.
abstract: BACKGROUND
  Previous studies showed the prognostic and predictive impact of human epidermal growth factor receptor 2 (HER-2) gene alterations analyzed separately and jointly with topoisomerase II α (TOP2A) gene alterations; however, the role of TOP2A gene abnormalities alone has not been thoroughly investigated. Additionally, TOP2A aberrations were typically studied in HER-2-positive (HER-2(+)) tumors because these genes are frequently coamplified. Therefore, the knowledge concerning the impact of TOP2A abnormalities in HER-2-negative (HER-2(-)) patients is scarce. This study aimed to investigate the clinical significance of TOP2A anomalies in breast cancer patients with HER-2(-) and HER-2(+) tumors.
  
  
  METHODS
  Snap-frozen tumor samples from 322 consecutive stage I-III breast cancer patients were analyzed for TOP2A gene dosage using quantitative real-time PCR (qPCR).
  
  
  RESULTS
  A high TOP2A gene dosage was found in 94 tumors (29%)-32% and 27% of HER-2(+) and HER-2(-) tumors, respectively. The mean TOP2A gene dosages in the HER-2(+) and HER-2(-) groups were 1.49 ± 1.03 and 1.09 ± 0.35, respectively. High TOP2A gene dosage had an inverse prognostic impact in terms of shorter disease-free survival (DFS) and overall survival (OS) times in the entire group and in both the HER-2(-) and HER-2(+) subgroups. The unfavorable prognostic impact of TOP2A gene dosage was maintained in the multivariate Cox regression analysis in the entire group and in HER-2(-) patients.
  
  
  CONCLUSIONS
  A high gene dosage of TOP2A determined using qPCR occurs frequently both in HER-2(+) and HER-2(-) tumors and has a strong adverse prognostic impact.
authors.affiliation: Laboratory of Cell Biology, Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Dêbinki 1, 80-211 Gdańsk, Poland. azaczek@gumed.edu.pl
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Zaczek
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Markiewicz
authors.forename: Barbara
authors.initials: B
authors.lastname: Seroczynska
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Skokowski
authors.forename: Janusz
authors.initials: J
authors.lastname: Jaskiewicz
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Pienkowski
authors.forename: Wojciech P
authors.initials: WP
authors.lastname: Olszewski
authors.forename: Jolanta
authors.initials: J
authors.lastname: Szade
authors.forename: Piotr
authors.initials: P
authors.lastname: Rhone
authors.forename: Marzena
authors.initials: M
authors.lastname: Welnicka-Jaskiewicz
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009367:Neoplasm Staging; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency* / Q000378:metabolism
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