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Amplification of the HER2 gene in breast cancers testing 2+ weak positive by HercepTest immunohistochemistry: false-positive or false-negative immunohistochemistry?
  1. Ciara Barrett,
  2. Hilary Magee,
  3. Denise O’Toole,
  4. Sinead Daly,
  5. Michael Jeffers
  1. Department of Cellular Pathology, The Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland
  1. Correspondence to:
 Dr M Jeffers
 Laboratory Medicine Department, The Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland; michael.jeffers{at}amnch.ie

Abstract

Background: The majority of cases of breast cancer scoring HER2 weak positive (2+) on immunohistochemistry (IHC) using the HercepTest are not associated with amplification of the HER2/neu gene.

Aim: To examine the reproducibility of IHC in cases scoring 2+ subsequently shown to have gene amplification by fluorescence in-situ hybridisation (FISH).

Methods: A retrospective analysis of 153 cases referred for FISH confirmation of a weak positive HercepTest (2+) result was performed. Repeat IHC was undertaken in cases with weak positive (2+) referral IHC and amplification of the HER2 gene by FISH.

Results: Amplification of the HER2 gene was confirmed in 29/153 cases (19%) scoring 2+ on IHC. Repeat IHC was carried out on 25 IHC 2+ cases: 7 (28%) scored 2+ on repeat IHC, 18 (72%) scored 3+ and were reclassified as strong positive. A heterogeneous expression pattern was present in 3/17 cases scoring 3+.

Conclusions: The majority of HercepTest 2+ results are not accompanied by gene amplification and represent “false positive” IHC in terms of prognostic or therapeutic relevance. A small proportion of HercepTest 2+ scores represent true 2+ IHC positive cases accompanied by gene amplification: a category probably biologically related to 3+ IHC cases. The remainder of cases of HercepTest™ 2+ accompanied by gene amplification represent a category of referral IHC 2+ weak positive, FISH amplified, repeat IHC 3+ strong positive, best described as “false negative 2+ IHC”. This has implications for selection of cases for FISH analysis where weak positive (2+) IHC score is used as a triage for FISH testing, and for testing strategies in referral laboratories undertaking FISH analysis.

  • AMNCH, The Adelaide and Meath Hospital
  • FISH, fluorescence in-situ hybridisation
  • IHC, immunohistochemistry

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Footnotes

  • Published Online First 5 July 2006

  • Competing interests: None.

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