Correlations of TOP2A gene aberrations and expression of topoisomerase IIα protein and TOP2A mRNA expression in primary breast cancer: a retrospective study of 86 cases using fluorescence in situ hybridization and immunohistochemistry

Pathol Int. 2012 Jun;62(6):391-9. doi: 10.1111/j.1440-1827.2012.02808.x. Epub 2012 Mar 23.

Abstract

Our aim in this study was to assess the status of TOP2A gene aberrations (no change/amplification or deletion) and its correlations with topoisomerase IIα (Topo IIα) protein and TOP2A mRNA expression, respectively. TOP2A amplification, Topo IIα protein expression and TOP2A mRNA expression were assessed using samples of 86 cases of breast cancer by fluorescence in fluorescence in situ hybridization, quantitative real-time polymerase chain reaction and immunohistochemistry, respectively. Twenty two (22.57%) had amplification/deletion of TOP2A gene. Twenty eight (32.56%) tumor samples were 17q polysomy or monosomy. Topo IIα protein was expressed in 57 cases (66.27%, 57/86): 22 cases (38.62%, 22/57) and 35 cases (61.40%, 35/57) had amplification/deletion and no change of TOP2A gene, respectively. These three groups showed significant differences by one-way analysis of variance (P < 0.001). The average Ct values of TOP2A mRNA expression in the tumors with deletion, amplification and no change of TOP2A gene were 27.00, 27.33 and 31.66, respectively. We demonstrated that the TOP2A gene was amplified or deleted in breast cancer, with a significant correlation with high expressions of Topo IIα protein and TOP2A mRNA expression. Ki-67 expression index (mean = 14.9) decreased significantly in cases wherein TOP2A gene had no change and Her2/neu protein expression was weakly positive (0-1+, P < 0.001).

MeSH terms

  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carcinoma, Intraductal, Noninfiltrating / genetics*
  • Carcinoma, Intraductal, Noninfiltrating / metabolism
  • Carcinoma, Intraductal, Noninfiltrating / mortality
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Carcinoma, Lobular / genetics*
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / mortality
  • Carcinoma, Lobular / pathology
  • China / epidemiology
  • DNA Topoisomerases, Type II / genetics*
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Amplification*
  • Gene Deletion*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry / methods
  • In Situ Hybridization, Fluorescence / methods
  • Middle Aged
  • Poly-ADP-Ribose Binding Proteins
  • RNA, Messenger / metabolism
  • Retrospective Studies
  • Survival Rate

Substances

  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • Poly-ADP-Ribose Binding Proteins
  • RNA, Messenger
  • DNA Topoisomerases, Type II
  • TOP2A protein, human