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Characterization of HER2 gene amplification heterogeneity in invasive and in situ breast cancer using bright-field in situ hybridization

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Abstract

The aims of this study were to evaluate and compare the HER2 gene amplification status in invasive and adjacent in situ breast carcinoma, using bright-field in situ hybridization, and to document the possible presence of HER2 genetic heterogeneity (HER2-GH) in both components. A cohort of 100 primary invasive carcinomas (IC) associated with carcinoma in situ (CIS) were evaluated for HER2 gene amplification by SISH according to the 2013 ASCO/CAP HER2 guideline. A second cohort of all the cases with HER2-GH since the introduction of the updated ASCO/CAP HER2 guideline was also characterized, and an evaluation of the HER2 gene amplification in the CIS component, if present, was also done. In the first cohort, the HER2 amplification in the IC was negative in 87% of the cases and positive in 13% of the cases, without the presence of HER2-GH. All the cases had an associated CIS with the same HER2 status as IC, with four cases of CIS presenting HER2-GH. In the CIS, we observed a significant relationship of HER2 gene amplification with high nuclear grade. In the four cases with HER2-GH in CIS, two cases presented HER2 gene amplification in the IC. The second cohort included 12 cases with HER2-GH in a total of 1243 IC cases (0.97%). Additionally, we identified two cases associated with non-amplified CIS. HER2-GH is a rare event in IC and can already be present in CIS, not being an important step in the acquisition of invasive features.

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Authors and Affiliations

  1. Department of Pathology, Ipatimup Diagnostics, Ipatimup–Institute of Molecular Pathology and Immunology of the University of Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal

    António Polónia, Guilherme Oliveira & Fernando Schmitt

  2. Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal

    António Polónia & Fernando Schmitt

  3. Laboratoire national de santé, 1, rue Louis Rech, 3555, Dudelange, Luxembourg

    Fernando Schmitt

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  1. António Polónia
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  2. Guilherme Oliveira
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  3. Fernando Schmitt
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Correspondence to Fernando Schmitt.

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This study has been performed in accordance with the national regulative law for the handling of biological specimens from tumor banks, being the samples exclusively available for research purposes in retrospective studies, as well as under the international Helsinki declaration.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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The authors declare that they have no conflict of interest.

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Polónia, A., Oliveira, G. & Schmitt, F. Characterization of HER2 gene amplification heterogeneity in invasive and in situ breast cancer using bright-field in situ hybridization. Virchows Arch 471, 589–598 (2017). https://doi.org/10.1007/s00428-017-2189-9

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  • DOI: https://doi.org/10.1007/s00428-017-2189-9

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