Topoisomerase 2α status in invasive breast carcinoma - comparison of its clinical value according to immunohistochemical and fluorescence in situ hybridization methods of evaluation

Pol J Pathol. 2014 Dec;65(4):283-90. doi: 10.5114/pjp.2014.48189.

Abstract

The main purpose of the study was to compare topoisomerase 2α (TOP2A) status in invasive breast carcinomas to the outcome of a therapy containing neoadjuvant treatment with anthracyclines (a combination chemotherapy treatment for breast cancer, namely AC [cyclophosphamide, doxorubicin]). To achieve these goals we created a method of evaluation with criteria based on two methods used in the present study (immunohistochemical [IHC] and fluorescence in situ hybridization [FISH]). The threshold for positive immunohistochemically evaluated status was set for all cases with: nuclear stain intensity score 3+ in 10% or more nuclei and nuclear stain intensity score 2+ in 50% or more nuclei. Our results suggest that TOP2A status may be used as a predictive factor for patient selection for protocols which include anthracyclines as one of the chemotherapeutics. Both methods, IHC and FISH, are suitable for implementation for diagnostic purposes, but IHC positive status measured according to the criteria presented above is the best predictor of longer disease-free survival (DFS) according to our study. Immunohistochemical also gave satisfactory results in all analyzed cases in comparison to only 60% of cases analyzed by FISH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracyclines / therapeutic use*
  • Antigens, Neoplasm / metabolism*
  • Antineoplastic Combined Chemotherapy Protocols
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology*
  • Carcinoma, Ductal, Breast / drug therapy
  • Carcinoma, Ductal, Breast / enzymology*
  • Chemotherapy, Adjuvant
  • DNA Topoisomerases, Type II / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Poly-ADP-Ribose Binding Proteins

Substances

  • Anthracyclines
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Poly-ADP-Ribose Binding Proteins
  • DNA Topoisomerases, Type II
  • TOP2A protein, human