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Impact of immunohistochemistry staining conditions on the incidence of human epidermal growth factor receptor 2 (HER2)-low breast cancer

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Abstract

We investigated frequencies of HER2-low breast cancer (BC) (immunohistochemistry [IHC] 1+ or 2+ without gene amplification) before and after IHC conditions were modified in order to understand the impact of IHC staining conditions on frequencies of HER2-low BC. Primary BC cases diagnosed at the Yeungnam University Hospital (YUH, n = 728) or Keimyung University Dongsan Hospital (KUDH, n = 290) in 2022 were reviewed, and data on HER2 status and IHC conditions were collected (cohort 1). Both institutions used the 4B5 antibody for HER2 IHC but had different staining protocols. After modifications of the IHC conditions at both institutions, primary BC cases (YUH, n = 324 and KUDH, n = 135) diagnosed from April to July 2023 (cohort 2) were reviewed to assess any changes in the frequency of HER2 status. In cohort 1, of the 728 cases diagnosed at YUH, 556 (76.4%) were HER2-zero, 76 (10.4%) were HER2-low, and 96 (13.2%) were HER2-positive, and of the 290 cases diagnosed at KUDH, 135 (46.6%) were HER2-zero, 82 (28.3%) were HER2-low, and 73 (25.2%) were HER2-positive. Modifications in HER2 IHC staining conditions dramatically increased the frequencies of HER2-low BC in cohort 2 (YUH 38.9% and KUDH 49.6%), but they did not result in significant changes in the HER2-positive rates (YUH 15.4% and KUDH 25.2%) compared to cohort 1. In conclusion, minor modifications in HER2 IHC staining conditions significantly affected the frequency of HER2-low BC but had little impact on the HER2-positivity rate. Each pathology laboratory should verify IHC conditions using control slides (including 1+) to enable the accurate identification of HER2-low BC.

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Data Availability

The data used in the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by a Yeungnam University Research Grant (2020).

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Author notes

  1. Min Chong Kim and Sun Young Kwon contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Yeungnam University College of Medicine, Daegu, Republic of Korea

    Min Chong Kim & Young Kyung Bae

  2. Department of Pathology, Keimyung University School of Medicine, Daegu, Republic of Korea

    Sun Young Kwon & Hye Ra Jung

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  1. Min Chong Kim
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Contributions

MCK collected the clinicopathological data, evaluated the slides, analyzed the data, and wrote the manuscript. SYK participated in the study design, collected the clinicopathological data, evaluated the slides, analyzed the data, and wrote the manuscript. HRJ collected the clinicopathological data and evaluated the slides. YKB conceived the study, evaluated clinicopathological data and slides, analyzed the data, and critically reviewed and revised the manuscript. All authors agreed with the submission of the manuscript for publication.

Corresponding author

Correspondence to Young Kyung Bae.

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Compliance with ethical standards

This retrospective study involving patients’ medical records and pathologic slides (HER2 immunohistochemistry and silver in situ hybridization) was approved by the Institutional Review Board of Yeungnam University Hospital (YUMC 2023-10-046) and the Keimyung University Dongsan Hospital (DSMC2023-11-026), which waived the requirement for informed consent.

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The authors declare no competing interests.

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Supplementary information

ESM 1

Supplementary Table S1 Comparison of HER2 IHC results before (cohort 1) and after (cohort 2) modifying immunohistochemical staining conditions by specimen types at both institutions (DOCX 13 kb)

ESM 2

Supplementary Fig S1 HER2 IHC results of PATHWAY HER2 4 in 1 control slides using the original and modified protocols in cohorts 1 and 2, respectively (DOCX 1.90 MB)

ESM 3

Supplementary Fig S2 Representative figures for SISH analysis on IHC 3+ cases (DOCX 1371 kb)

ESM 4

Supplementary Fig S3 Comparisons of core needle biopsy (CNB) and subsequent resection specimen HER2 IHC scores in cohort 2 at YUH (A) and KUDH (B) (DOCX 257 kb)

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Kim, M.C., Kwon, S.Y., Jung, H.R. et al. Impact of immunohistochemistry staining conditions on the incidence of human epidermal growth factor receptor 2 (HER2)-low breast cancer. Virchows Arch (2024). https://doi.org/10.1007/s00428-024-03824-6

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  • DOI: https://doi.org/10.1007/s00428-024-03824-6

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