Heterogeneous HER2 Gene Amplification Impact on Patient Outcome and a Clinically Relevant Definition

Research output: Contribution to journalArticle

Authors

  • AI Bartlett
  • J Starcyznski
  • T Robson
  • A MacLellan
  • FM Campbell
  • CJH van de Vekle
  • A Hasenburg
  • C Markopoulos
  • C Seynaeve
  • JMS Bartlett

Colleges, School and Institutes

Abstract

Heterogeneous expression or amplification is a challenge to HER2 diagnostics. A guideline defines heterogeneity as the presence of between 5% and 50% cells with HER2/CEP17 ratios of more than 2.20. We audited the frequency of such cells and their clinical impact in the results from 2 pathology laboratories combined with data from the TEAM [Tamoxifen vs Exemestane Adjuvant Multicentre] pathology study. HER2 reports were scanned and the percentages of amplified cells reported. Of 6,461 eligible cases, 754 (11.7%) exhibited 50% or more cells with ratios of more than 2.20, which is "amplified" by College of American Pathologists guidelines. Of the cases, 2,166 (33.5%) exhibited more than 5% but less than 50% of cells with HER2/CEP17 ratios of more than 2.20, or "heterogeneous amplification." No prognostic impact was observed when fewer than 30% of cells exhibited ratios of more than 2.20. All amplified cases with 30% to 50% of cells with ratios more than 2.20 were identified as such by United Kingdom guidelines. The percentage of tumor cells with HER2/CEP17 ratios more than 2.20 does not identify cases with heterogeneous amplification or poor outcome. A modified approach for identification of true heterogeneous amplification is suggested.

Details

Original languageEnglish
Pages (from-to)266-274
Number of pages9
JournalAmerican Journal of Clinical Pathology
Volume136
Issue number2
Publication statusPublished - 1 Aug 2011

Keywords

  • Amplification, HER2, Breast, Heterogeneity