title: TOP2A amplification in the absence of that of HER-2/neu: toward individualization of chemotherapeutic practice in breast cancer.
abstract: OBJECTIVE
  To investigate the relationship between human epidermal growth factor receptor (HER)-2/neu and the gene encoding topoisomerase IIα (TOP2A) in breast cancer, while elucidating their association with clinicopathological variables.
  
  
  METHODS
  Real-time quantitative polymerase chain reaction (RQ-PCR) was performed on a 96-patient study group to assess gene amplification, and levels were determined using the comparative cycle threshold approach and Taqman assays. An immunohistochemistry (IHC) microarray (n = 76) was then employed to check for correlation between gene amplification and protein expression levels.
  
  
  RESULTS
  Amplification levels of TOP2A did not differ significantly according to HER-2/neu status by either RQ-PCR or IHC microarray. Of the HER-2/neu(-) patients, 29.1% demonstrated levels of TOP2A above the third quartile, whereas 22.9% of the HER-2/neu(+) patients had values in the first quartile (log TOP2A <0.62), thereby indicating low-level amplification. Of the 60 patients characterized as HER-2/neu(-) using IHC and fluorescence in situ hybridization (FISH), 22.9% were classified as TOP2A(+) on the IHC microarray. Of the 14 patients deemed HER-2/neu(+) using IHC and FISH, meanwhile, the majority (n = 10) were classified as TOP2A(+).
  
  
  CONCLUSIONS
  Our results indicate that amplification of TOP2A in breast cancer is not confined to those who are concomitantly HER-2/neu(+), and suggest that a significant proportion of HER-2/neu(-) patients exhibit high levels of TOP2A.
authors.affiliation: Department of Surgery, Clinical Science Institute, National University of Ireland, Galway, Ireland.
authors.forename: Ronan W
authors.initials: RW
authors.lastname: Glynn
authors.forename: Sarah
authors.initials: S
authors.lastname: Mahon
authors.forename: Catherine
authors.initials: C
authors.lastname: Curran
authors.forename: Grace
authors.initials: G
authors.lastname: Callagy
authors.forename: Nicola
authors.initials: N
authors.lastname: Miller
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kerin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*
chemical_list: D000951:Antigens, Neoplasm; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D000075223:Poly-ADP-Ribose Binding Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C000618811:TOP2A protein, human