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Co-amplification of the HER2 gene and chromosome 17 centromere: a potential diagnostic pitfall in HER2 testing in breast cancer

Varga, Zsuzsanna ; Tubbs, Raymond ; Wang, Zhen ; Sun, Yang ; Noske, Aurelia ; Kradolfer, Doris ; Bosshard, Giovanna ; Jochum, Wolfram ; Moch, Holger ; Öhlschlegel, Christian

In: Breast Cancer Research and Treatment, 2012, vol. 132, no. 3, p. 925-935

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    Titre
    • Co-amplification of the HER2 gene and chromosome 17 centromere: a potential diagnostic pitfall in HER2 testing in breast cancer
    Auteur
    • Varga, Zsuzsanna. Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland
    • Tubbs, Raymond. Section of Molecular Oncologic Pathology, Department of Molecular Pathology, Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
    • Wang, Zhen. Section of Molecular Oncologic Pathology, Department of Molecular Pathology, Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
    • Sun, Yang. Section of Molecular Oncologic Pathology, Department of Molecular Pathology, Pathology and Laboratory Medicine Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
    • Noske, Aurelia. Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland
    • Kradolfer, Doris. Institute of Pathology, Cantonal Hospital, St. Gallen, Switzerland
    • Bosshard, Giovanna. Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland
    • Jochum, Wolfram. Institute of Pathology, Cantonal Hospital, St. Gallen, Switzerland
    • Moch, Holger. Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland
    • Öhlschlegel, Christian. Institute of Pathology, Cantonal Hospital, St. Gallen, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Breast Cancer Research and Treatment, 2012, vol. 132, no. 3, p. 925-935. Springer US; http://www.springer-ny.com
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:321000
    Summary
    Co-amplification of the centromere on chromosome 17 (CEP17) and HER2 can occur in breast cancer. Such aberrant patterns (clusters) on CEP17 can be misleading to calculate the HER2/CEP17 ratio, and thus underreporting of HER2 amplification. We identified 14 breast cancers retrospectively with HER2/CEP17 co-amplification and performed FISH (fluorescence in situ hybridization) with additional chromosome 17 probes (17p11.1-q11.1, 17p11.2-p12, TP53 on 17p13.1, RARA on 17q21.1-3 and TOP2 on 17q21.3-22) to characterize the spanning of the amplicon in these cases. Furthermore, the HER2 status was analyzed by means of HER2 silver in situ hybridization (SISH) and immunohistochemistry (IHC). The co-amplification of HER2/CEP17 was compared between the three institutions. TP53 was eusomic in all cases, 17p11.2-p12 in 79% (11/14), whereas 17p11.1-q11.1 showed chromosomal gain in all cases. RARA was amplified in 10/14 cases (71%) and TOP2 in 3/14 cases (21%). HER2 was amplified with FISH/SISH in all 14 cases. 9/14 tumors were 3+ IHC positive (64%) and 3 cases were 2+ IHC positive. In our cohort the CEP17 amplicon almost always involves the HER2 but not the TOP2 locus. Overall agreement on HER2/CEP17 ratio (when applying ASCO/CAP guidelines) was only 64% (9/14 cases) between the institutions. Discrepant ratios varied from 1.1 to 14.3. The HER2/CEP17 co-amplification is not defined in the ASCO/CAP guidelines, and may result in inaccurate HER2-FISH/SISH status, particularly if only the calculated HER2/CEP17 ratio is reported. It is recommended to report separate CEP17 and HER2 signals in complex HER2/CEP17 patterns