title: Prognostic value of TOP2A gene amplification and chromosome 17 polysomy in early breast cancer.
abstract: The aim of this study was to analyze the occurrence of TOP2A gene amplification and chromosome 17 polysomy in patients with early breast cancer and to correlate the status of these alterations with the prognostic significance expressed as patients' clinical features and survival. Such concurrent analyses of TOP2A gene status and chromosome 17 polysomy have not been performed before. Study group included 149 consecutive stage I-III patients administered standard multimodality treatment. TOP2A abnormalities were examined by standard fluorescence in situ hybridization (FISH) and developed by our group quantitative real-time PCR (qPCR). TOP2A amplification and deletion assessed by FISH were found in 23% and 7% of the tumours, respectively, and by qPCR in 31% and 11% of the tumours, respectively. Chromosome 17 polysomy was detected in 40% of the cases. TOP2A amplification (by qPCR) correlated with shorter disease-free survival (p = 0.03) and overall survival (p = 0.047), and the prognostic value of TOP2A was confirmed in the multivariate analysis (HR = 3.22, 95% CI 1.09-9.56, p = 0.03). TOP2A gene amplification, but not chromosome 17 polysomy, carries negative prognostic information in early breast cancer. Given the aforementioned results, qPCR might serve as a prognostic tool in determining the patient's prognosis.
authors.affiliation: Laboratory of Cell Biology, Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Dębinki 1, 80-211, Gdańsk, Poland. azaczek@gumed.edu.pl
authors.forename: Anna
authors.initials: A
authors.lastname: Zaczek
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Markiewicz
authors.forename: Anna
authors.initials: A
authors.lastname: Supernat
authors.forename: Natalia
authors.initials: N
authors.lastname: Bednarz-Knoll
authors.forename: Burkhardt
authors.initials: B
authors.lastname: Brandt
authors.forename: Barbara
authors.initials: B
authors.lastname: Seroczyńska
authors.forename: Jarosław
authors.initials: J
authors.lastname: Skokowski
authors.forename: Jolanta
authors.initials: J
authors.lastname: Szade
authors.forename: Piotr
authors.initials: P
authors.lastname: Czapiewski
authors.forename: Wojciech
authors.initials: W
authors.lastname: Biernat
authors.forename: Marzena
authors.initials: M
authors.lastname: Wełnicka-Jaśkiewicz
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000782:Aneuploidy; D000951:Antigens, Neoplasm / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human