Breast Cancer Research and Treatment

, Volume 155, Issue 3, pp 457–462 | Cite as

HER2 FISH classification of equivocal HER2 IHC breast cancers with use of the 2013 ASCO/CAP practice guideline

  • Yao-Shan Fan
  • Carmen E. Casas
  • Jinghong Peng
  • Melanie Watkins
  • Lynn Fan
  • Jennifer Chapman
  • Offiong Francis Ikpatt
  • Carmen Gomez
  • Wei Zhao
  • Isildinha M. Reis
Preclinical study


The status of human epidermal growth factor receptor 2 (HER2, ERBB2) determines the eligibility of breast cancer patients to receive HER2-targeted therapy. The majority of HER2 testing in the U.S. is performed using a combination of immunohistochemistry (IHC) screening followed by fluorescence in situ hybridization (FISH) for IHC equivocal cases. In 2013, the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) updated the guideline for HER2 testing. This study evaluates the impact of the 2013 ASCO/CAP updated guideline on final HER2 FISH classification of breast cancers with an equivocal IHC result. For each case, we reported a FISH result according to the 2013 updated guideline and recorded a separated result using the 2007 guideline for investigational purpose. McNemar’s test and Bowker’s symmetry test were used to compare the classifications by the two guidelines. Among 172 HER2 IHC 2+ equivocal cases, use of the 2103 guideline changed classifications in 36 cases (21 %) when compared with the results expected by use of the 2007 guideline, and yielded a higher proportion of positive (28.5 vs. 23.3 %) and equivocal (16.3 vs. 4.1 %), and a lower proportion of negative (55.2 vs. 72.7 %) cases (p < 0.001). The major classification change with use of the updated guideline is from the HER2 FISH negative to equivocal in 26 cases (15 %). Our study has shown that implementation of the 2013 ASCO/CAP updated guideline has significant impact on HER2 classification for breast cancers with an equivocal HER2 IHC result and therefore increased the use of HER2-targeted therapy. Our data have also shown that reflex FISH is effective for final classification of the IHC equivocal cases and that polysomy 17 (CEP17 copy number ≥3/cell) is present in a significantly higher proportion of cases with an equivocal HER2 FISH classification.


Breast cancer HER2 Immunohistochemistry Fluorescence in situ hybridization ASCO/CAP practice guideline Polysomy 17 


Compliance with ethical standards

Conflict of interest

All authors declare that they no have no conflict interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Yao-Shan Fan
    • 1
  • Carmen E. Casas
    • 1
  • Jinghong Peng
    • 1
  • Melanie Watkins
    • 1
  • Lynn Fan
    • 1
  • Jennifer Chapman
    • 1
  • Offiong Francis Ikpatt
    • 1
  • Carmen Gomez
    • 1
  • Wei Zhao
    • 3
  • Isildinha M. Reis
    • 2
    • 3
  1. 1.Department of Pathology and Laboratory MedicineUniversity of Miami Miller School of MedicineMiamiUSA
  2. 2.Department of Public Health SciencesUniversity of Miami Miller School of MedicineMiamiUSA
  3. 3.Biostatistics and Bioinformatics Core Shared Resource, Sylvester Comprehensive Cancer CenterUniversity of Miami School of MedicineMiamiUSA

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