Document Detail


Amplification of the HER2 gene in breast cancers testing 2+ weak positive by HercepTest immunohistochemistry: false-positive or false-negative immunohistochemistry?
MedLine Citation:
PMID:  16822876     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ciara Barrett; Hilary Magee; Denise O'Toole; Sinead Daly; Michael Jeffers
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Publication Detail:
Type:  Journal Article     Date:  2006-07-05
Journal Detail:
Title:  Journal of clinical pathology     Volume:  60     ISSN:  0021-9746     ISO Abbreviation:  J. Clin. Pathol.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-06-11     Completed Date:  2007-07-26     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  0376601     Medline TA:  J Clin Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  690-3     Citation Subset:  AIM; IM    
Affiliation:
Department of Cellular Pathology, The Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland.
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MeSH Terms
Descriptor/Qualifier:
Breast Neoplasms / genetics*,  metabolism,  pathology
False Negative Reactions
False Positive Reactions
Female
Genes, erbB-2
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Neoplasm Invasiveness
Neoplasm Proteins / metabolism
Receptor, erbB-2 / metabolism*
Retrospective Studies
Tumor Markers, Biological / metabolism*
Chemical
Reg. No./Substance:
0/Neoplasm Proteins; 0/Tumor Markers, Biological; EC 2.7.10.1/Receptor, erbB-2
Comments/Corrections

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