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Comparison of HER2 amplification status among breast cancer subgroups offers new insights in pathways of breast cancer progression

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Abstract

Although the prognostic and predictive significance of human epidermal growth factor receptor 2 (HER2) in invasive breast cancer is well established, its role in ductal carcinoma in situ (DCIS) remains unclear. Reports on combined evaluation of both HER2 protein expression and HER2 amplification status in pure DCIS and DCIS adjacent to invasive ductal carcinoma (i.e., admixed DCIS) are scarce. In this study, immunohistochemistry and fluorescence in situ hybridization (FISH) were used to assess HER2 status in 72 cases of pure DCIS, 73 cases of DCIS admixed with invasive ductal carcinoma (IDC), and 60 cases of pure IDC. HER2 copy number-based amplification was present in 49% of pure DCIS, 16% of admixed DCIS, 18% of admixed IDC, and 8% of pure IDC. Amplified pure DCIS with clusters of HER2 signals showed a significantly lower HER2 copy number than amplified admixed DCIS with clusters. Whereas pure DCIS and admixed DCIS presented significant differences, the in situ and invasive component of admixed tumors showed striking similarities regarding mean HER2 and chromosome 17 centromere (CEP17) copy number, grade, and estrogen and progesterone receptor expression. The discrepant prevalence of HER2 amplification among breast cancer subgroups indirectly suggests that HER2 may not play a crucial role in the transition of in situ to invasive breast cancer. The similarities in HER2 amplification status between the in situ and invasive component of admixed tumors hint at a common biological pathway for both components. Our data support the theory that pure DCIS, pure IDC, and admixed lesions have a common progenitor, but can progress as separate lineages.

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Abbreviations

CEP:

Chromosome enumeration probe

DCIS:

Ductal carcinoma in situ

ER:

Estrogen receptor

FISH:

Fluorescence in situ hybridization

HER2:

Human epidermal growth factor receptor 2

IDC:

Invasive ductal carcinoma

IHC:

Immunohistochemistry

PR:

Progesterone receptor

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Acknowledgements

We thank all lab technicians of the Department of Pathology and the Center for Molecular Pathology (Ghent University Hospital) for their excellent technical assistance.

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Authors and Affiliations

  1. Department of Pathology, AZ St Lucas Hospital, Groenebriel 1, 9000, Ghent, Belgium

    Kathleen Lambein

  2. Department of Oncology, KU Leuven, Surgical Oncology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium

    Kathleen Lambein

  3. Department of Medical and Forensic Pathology, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium

    Mieke Van Bockstal, Lies Vandemaele, Sofie Geenen & Louis Libbrecht

  4. Cancer Research Institute Ghent (CRIG), Ghent, Belgium

    Mieke Van Bockstal

  5. Department of Gynaecology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium

    Rudy Van den Broecke

  6. Department of Medical Oncology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium

    Veronique Cocquyt & Hannelore Denys

  7. Department of Pathology, University Clinics St Luc, Hippokrateslaan 10, 1200, Sint-Lambrechts-Woluwe, Belgium

    Louis Libbrecht

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  1. Kathleen Lambein
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Contributions

KL, MVB, HD, and LL designed the study, analyzed and interpreted the data, and drafted the manuscript. RVDB, VC, and HD acquired patient data. LVDM and SG coordinated and ensured the quality of all analyses. All authors contributed to, read, and approved the final manuscript.

Corresponding author

Correspondence to Louis Libbrecht.

Ethics declarations

This study has been approved by the ethics committee of Ghent University Hospital (Ghent, Belgium). The approval carries file number 2013/987 and the Belgian registration number B670201319010.

Funding

This study was funded by the ‘Klinisch onderzoeksfonds’ (clinical research fund; KL) and the ‘Speerpunt Oncologie’ (spearhead oncology; VC) from Ghent University Hospital, Ghent, Belgium.

Conflict of interest

Advisory role for Roche (KL).

The other authors declare no conflicts of interest.

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Lambein, K., Van Bockstal, M., Vandemaele, L. et al. Comparison of HER2 amplification status among breast cancer subgroups offers new insights in pathways of breast cancer progression. Virchows Arch 471, 575–587 (2017). https://doi.org/10.1007/s00428-017-2161-8

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