Amplification of HER2 and TOP2A and deletion of TOP2A genes in breast cancer investigated by new FISH probes

Karen E Olsen, Helle Knudsen, Birgitte Rasmussen, Eva Balslev, Ann Knoop, Bent Ejlertsen, Kirsten V Nielsen, Andreas Schønau, Jens Overgaard, Danish Breast Cancer Cooperative Group

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

New strategies for improving treatment of patients with breast carcinoma have focused on the HER2 oncoprotein with regard to response to traditional therapy regimes and the effect of a new drug specifically directed against the protein. Furthermore, the status of the topoisomerase IIalpha (TOP2A) gene has been suggested as a predictive marker of anthracycline treatment. In this study of 120 tumours, immunohistochemically detected HER2 overexpression with HercepTest has been compared to the HER2 gene amplification investigated with a new HER2 probe for fluorescence in situ hybridization (FISH). In addition, the HercepTest was evaluated as a screening tool for choosing cases for FISH investigation of TOP2A gene aberrations. The HercepTest score 3+ identified HER2 gene amplification in 27 of 30 amplified tumours (sensitivity of 0.90) with a false-negative rate of 0.10 and a false-positive rate of 0.06. TOP2A gene amplification or deletion was found in 20 cases. Sixteen (80%) of these carcinomas were in the HercepTest 3+ group, but four tumours had alterations in the TOP2A gene with normal HER2 status. Traditionally, in the FISH technique the result has been based on counting 60 cells. However, we found that a much less time-consuming method of counting 60 signals gave equally good results.

Original languageEnglish
JournalActa Oncologica
Volume43
Issue number1
Pages (from-to)35-42
Number of pages8
ISSN0284-186X
Publication statusPublished - 2004

Keywords

  • Adult
  • Aged
  • Biopsy, Needle
  • Breast Neoplasms
  • DNA Topoisomerases, Type II
  • Female
  • Gene Amplification
  • Gene Deletion
  • Gene Expression Regulation, Neoplastic
  • Genes, erbB-2
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Sensitivity and Specificity
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't

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