The Impact of Partial Weak Staining in Normal Breast Epithelium on the Reliability of Immunohistochemistry Results in HercepTest-positive Breast Cancer

Chantal Farra, Faysal Fedda, Arafat Tfayli, Ayman Tawil, Ghazi Zaatari, Hanin Ashkar, Grece Issa, Fouad Boulos

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Introduction: Although normal epithelial cells do not show human epidermal growth factor receptor-2 (HER2) gene amplification and should lack membrane staining by HER2 immunohistochemistry (IHC), HER2 staining in benign breast epithelium is occasionally encountered. The significance of this occurrence has not yet been adequately studied, and its associated American Society of Clinical Oncology/College of American Pathologists recommendations are vague. Our objective is to assess the correlation between HER2 IHC 3+ breast cancer cases with normal epithelium staining (NES) and their corresponding fluorescence in situ hybridization (FISH) results, and to suggest recommendations for interpretation. Materials and Methods: A total of 154 breast cancer cases with HER2 IHC 3+ were reviewed. NES, along with other clinicopathologic characteristics, were recorded. NES was scored as present or absent. All study cases were sent for FISH testing. All cases, and particularly those that showed false positivity for IHC (positive IHC, negative FISH) were examined for NES. Results: Of the 154 cases, 146 cases were FISH-positive (94.8%) and 2 failed FISH testing (1.3%). Conversely, 22% (34/154) of the cases showed NES for HER2. Of these 34 cases, 23 (67%) were FISH-amplified, 9 (26%) were FISH not amplified, and 2 failed FISH testing. Notably, all of the false-positive (FISH-negative) breast cancer cases showed some degree of positivity in normal breast epithelium. Conclusions: Our findings, though descriptive, show a very strong association between NES and false-positive HER2 IHC. This confirms the need to carefully evaluate IHC-positive breast cancers for NES, and to have a low threshold for confirmatory testing by FISH.

Original languageEnglish
Pages (from-to)340-344
Number of pages5
JournalClinical breast cancer
Volume19
Issue number5
DOIs
StatePublished - Oct 2019

Keywords

  • ASCO/CAP recommendations
  • False positive HER2
  • Fluorescent in-situ hybridization
  • HER2 gene amplification
  • Normal breast epithelium

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