title: Amplification of HER2 and TOP2A and deletion of TOP2A genes in a series of Taiwanese breast cancer.
abstract: BACKGROUND
  The prognostic relevance of topoisomerase II alpha (TOP2A) copy number change remains not well established. This study is aimed to investigate the frequency and pattern of TOP2A aberrations; to correlate TOP2A alterations with human epidermal growth factor receptor 2 (HER2) status and clinicopathological parameters, and further to explore prognostic value of TOP2A and HER2 status in breast cancer in Taiwan.
  
  
  METHODS
  We analyzed tissue samples from 311 invasive carcinomas in tissue microarrays for TOP2A and HER2 status by fluorescent in situ hybridization.
  
  
  RESULTS
  TOP2A copy number change is an infrequent genetic event (9.8% amplification and 2.7% deletion) and is present in both HER2-amplified and nonamplified tumors. TOP2A amplification is statistically associated with age >50 at diagnosis (P = 0.016) and HER2 amplification (P < 0.001). HER2 amplification, but not TOP2A amplification, is a predictor of unfavorable prognosis (P = 0.002). Univariate and multivariate analysis showed that higher histologic grading, positive nodal involvement, and HER2 positivity were associated with poorer overall survival. Cytogenetically, double minutes-type amplification is the predominant pattern for both genes (HER2: 64% and TOP2A: 93.1%). Homogeneous staining region-type signals of both genes are resistant to RNase digestion, supporting that these were not nuclear accumulation of mRNA transcripts.
  
  
  CONCLUSIONS
  Our results demonstrate the prognostic value of tumor grading, nodal involvement, and HER2 status in Taiwanese breast cancer. TOP2A aberrations are an infrequent event independent of HER2 status, and TOP2A amplification carries no prognostic value. The predictive value of TOP2A aberrations in patients of breast cancer taking athracycline-containing treatment in Taiwan remains to be determined in prospectively well-designed clinical trials.
authors.affiliation: aDepartment of Pathology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan bCollege of Medicine, Chang Gung University, Kwei-Shan, Taoyuan, Taiwan cDepartment of Nephrology, Division of Medicine Keelung Chang Gung Memorial Hospital, Keelung, Taiwan dDepartment of General Surgery, Division of Surgery, Keelung Chang Gung Memorial Hospital, Taiwan eDepartment of Oncology and Hematology, Division of Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan fDepartment of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Jim-Ray
authors.initials: JR
authors.lastname: Chen
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Chien
authors.forename: Kuo-Su
authors.initials: KS
authors.lastname: Chen
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Hwang
authors.forename: Huang-Yang
authors.initials: HY
authors.lastname: Chen
authors.forename: Kun-Yan
authors.initials: KY
authors.lastname: Yeh
authors.forename: Tsan-Yu
authors.initials: TY
authors.lastname: Hsieh
authors.forename: Liang-Che
authors.initials: LC
authors.lastname: Chang
authors.forename: Yuan-Chun
authors.initials: YC
authors.lastname: Hsu
authors.forename: Ren-Jie
authors.initials: RJ
authors.lastname: Lu
authors.forename: Chung-Ching
authors.initials: CC
authors.lastname: Hua
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics*; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D056915:DNA Copy Number Variations; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins; D016019:Survival Analysis; D013624:Taiwan / Q000453:epidemiology
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human