Clinical significance of topoisomerase 2A expression and gene change in operable invasive breast cancer

Tumour Biol. 2015 Sep;36(9):6833-8. doi: 10.1007/s13277-015-3390-6. Epub 2015 Apr 7.

Abstract

This study aims to investigate clinical significance of topoisomerase 2A (TOP2A) expression and TOP2A gene change in operable invasive breast cancer. This is a retrospective analysis, which includes 256 patients diagnosed as operable invasive breast cancer. All postoperational waxed specimens were subjected to resectioning for staining. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), KI-67, TOP2A expression, and TOP2A gene changes were detected by immunohistochemistry (IHC) and fluorescent in situ hybridization technique (FISH), respectively. Correlation between TOP2A expression and clinicopathological characteristics was also investigated. Effects of TOP2A protein or gene changes on survival rate were detected. Results indicated that 165 were TOP2A positive (64.5 %), and 31 were gene amplification positive (12.1 %). Positive rate of TOP2A expression showed significant correlations with ER, KI-67, and HER-2. The difference of 5-year overall survival (OS) between TOP2A-positive and TOP2A-negative groups did not reach statistical significance (OS: P = 0.321, 85.9 vs. 79.6 %; disease-free survival [DFS]: P = 0.247, 83.3 vs. 75.3 %). Five-year OS in TOP2A amplification group was 68.8 %, which is lower than deficiency and control group (P > 0.05). Subgroup analysis showed no significant differences of OS and DFS either between TOP2A-positive and TOP2A-negative groups or between TOP2A amplification and control group in population of patients with HER-2 amplification, triple negative breast cancer, or hormone-positive breast cancer. In conclusion, positive rate of TOP2A expression correlates significantly with ER, KI-67, and HER-2. However, prognostic significance of either TOP2A expression or TOP2A gene changes in breast cancer and its various subtypes is limited.

Keywords: Clinical significance; Immunohistochemistry; Operable invasive breast cancer; Situ hybridization technique; Topoisomerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / biosynthesis*
  • Antigens, Neoplasm / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • DNA Topoisomerases, Type II / biosynthesis*
  • DNA Topoisomerases, Type II / genetics
  • DNA-Binding Proteins / biosynthesis*
  • DNA-Binding Proteins / genetics
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Situ Hybridization, Fluorescence
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Poly-ADP-Ribose Binding Proteins
  • Prognosis
  • Receptor, ErbB-2 / biosynthesis
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / biosynthesis
  • Receptors, Estrogen / genetics
  • Receptors, Progesterone / biosynthesis
  • Receptors, Progesterone / genetics

Substances

  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • Poly-ADP-Ribose Binding Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • DNA Topoisomerases, Type II
  • TOP2A protein, human