title: Multiplication of Chromosome 17 Centromere Is Associated with Prognosis in Patients with Invasive Breast Cancers Exhibiting Normal HER2 and TOP2A Status.
abstract: OBJECTIVE
  This study aimed to investigate the clinical significance of chromosome 17 centromere (CEP17) multiplication (increased copy number of CEP17) related to human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) status in patients with invasive breast cancer.
  
  
  METHODS
  We constructed tissue microarrays using 594 invasive breast cancer samples and performed single-color silver-enhanced in situ hybridization (SISH) assay for HER2, TOP2A, and CEP17 to assess for copy number aberrations. The association of CEP17 multiplication with patient survival was analyzed according to HER2 and TOP2A status.
  
  
  RESULTS
  Among 567 informative cases, HER2 amplification was noted in 22.8%, TOP2A amplification in 8.3% and TOP2A deletion in 11.1%. CEP17 multiplication was identified in 33.2% and was significantly associated with worse overall survival (OS) (p=0.02) and disease-free survival (DFS) (p=0.02). CEP17 multiplication correlated with patient survival in patients with normal TOP2A or non-amplified HER2 status, but the prognostic significance was lost in those with altered TOP2A or amplified HER2. On multivariate analyses, CEP17 multiplication was an independent prognostic factor for poorer OS (p=0.02) and DFS (p=0.01) in patients with normal TOP2A and non-amplified HER2.
  
  
  CONCLUSIONS
  CEP17 multiplication was identified as a promising prognostic marker in patients with invasive breast cancer exhibiting either non-amplified HER2 or normal TOP2A status.
authors.affiliation: Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea.
authors.forename: Aeri
authors.initials: A
authors.lastname: Kim
authors.forename: Hyung Chan
authors.initials: HC
authors.lastname: Shin
authors.forename: Young Kyung
authors.initials: YK
authors.lastname: Bae
authors.forename: Min Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Su Hwan
authors.initials: SH
authors.lastname: Kang
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Lee
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Lee