Breast Cancer Research and Treatment

, Volume 175, Issue 1, pp 51–57 | Cite as

Impact of the updated 2018 ASCO/CAP guidelines on HER2 FISH testing in invasive breast cancer: a retrospective study of HER2 fish results of 2233 cases

  • Zhi-Hua Liu
  • Kun Wang
  • Dan-Yi Lin
  • Jie Xu
  • Jie Chen
  • Xiao-Yu Long
  • Yan Ge
  • Xin-Lan Luo
  • Ke-Ping Zhang
  • Yan-Hui Liu
  • Fang-Ping XuEmail author
Preclinical study



Human epidermal growth factor receptor 2 (HER2, ERBB2) is a valuable prognostic and predictive biomarker in breast cancer. Accurate assessment of HER2 status is essential in selecting the patients with invasive breast cancer who will likely response to HER2-targeted therapies. Some major modifications in the diagnostic recommendation for fluorescence in situ hybridization (FISH) have been made in the updated 2018 American Society of Clinical Oncology (ASCO)/College of American Pathologist (CAP) guideline. According to the revised guideline, concomitant IHC assays are required to arrive at the most accurate HER2 status designation after HER2 FISH equivocal results; however, little is known about its influence on the clinical practice of pathologist. The purpose of this study was to evaluate the impact of the revised 2018 ASCO/CAP guidelines on the HER2 status designation.


We retrospectively reviewed the HER2 FISH testing results from 2233 cases of invasive breast cancer between January 2014 and December 2017. Concomitant immunohistochemistry (IHC) were performed on the same tissue blocks that were used for the FISH testing.


Compared to the 2013 guidelines, the HER2 status in 183 (8.2%) cases were re-defined when reassessed by the 2018 guidelines. Among these 183 cases, 175 equivocal cases according to the 2013 guideline were re-defined as HER2 negative (n = 173) or HER2 positive (n = 2). Eight previously classified as HER2 positive cases were converted to negative in the 2018 scheme, all of which were with HER2 IHC scores of 1+ or 2+. The number of cases in the negative category was 1705 according to the 2018 guidelines as opposed to 1524 by the 2013 guidelines.


The updated 2018 ASCO/CAP guidelines eliminated the FISH equivocal category, which can be attributed to reflex HER2 IHC, and partly ease the dilemma for clinical practice. Reflex IHC for FISH equivocal cases is of prime importance; furthermore, HER2 FISH results were converted from positivity to negativity based on the concomitant IHC results in a small percentage of cases. In all, implementation of the 2018 ASCO/CAP guidelines provides much clearer instructions and recommendations for the HER2 status designation, and thus reduces the risk of misdiagnosis.


Breast cancer HER2 Immunohistochemistry Fluorescence in situ hybridization ASCO/CAP guidelines 



Human epidermal growth factor 2




Fluorescence in situ hybridization


American Society of Clinical Oncology


College of American Pathologists



We thank Hui–Hui Jiang for outstanding technical support and Zhi Li for constructive comments on the manuscript.


This study is supported by a grant from National Clinical Key Subject Construction Project Fund of China, and grant from Guangdong Medical Science and Technology Research Fund (No. A2016086).

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed involving human participants were in accordance with the ethical standards of the Institutional Review Board of Guangdong General Hospital, Guangdong Academy of Medical Sciences and with the 1964 Helsinki declaration and its later amendments.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Zhi-Hua Liu
    • 1
  • Kun Wang
    • 2
  • Dan-Yi Lin
    • 1
  • Jie Xu
    • 1
  • Jie Chen
    • 1
  • Xiao-Yu Long
    • 1
  • Yan Ge
    • 1
  • Xin-Lan Luo
    • 1
  • Ke-Ping Zhang
    • 1
  • Yan-Hui Liu
    • 1
  • Fang-Ping Xu
    • 1
    Email author
  1. 1.Department of Pathology and Laboratory Medicine, Guangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouPeople’s Republic of China
  2. 2.Department of Breast Cancer, Cancer Center, Guangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouPeople’s Republic of China

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