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Patterns of HER-2/neu Amplification and Overexpression in Primary and Metastatic Breast Cancer

Simon, Ronald ; Nocito, Antonio ; Hübscher, Tanja ; Bucher, Christoph ; Torhorst, Joachim ; Schraml, Peter ; Bubendorf, Lukas ; Mihatsch, Michael M. ; Moch, Holger ; Wilber, Kim ; Schötzau, Andreas ; Kononen, Juha ; Sauter, Guido

In: Journal of the National Cancer Institute, 2001, vol. 93, no. 15, p. 1141-1146

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    Titre
    • Patterns of HER-2/neu Amplification and Overexpression in Primary and Metastatic Breast Cancer
    Auteur
    • Simon, Ronald. Affiliations of authors: R. Simon, A. Nocito, T. Hübscher, C. Bucher, J. Torhorst, P. Schraml, L. Bubendorf, M. M. Mihatsch, H. Moch, G. Sauter (Institute of Pathology), A. Schötzau (Eye Clinic), University of Basel, Switzerland; K. Wilber, Vysis Inc., Downers Grove, IL; J. Kononen, Diomeda Life Sciences Inc., Rockville, MD.
    • Nocito, Antonio. Affiliations of authors: R. Simon, A. Nocito, T. Hübscher, C. Bucher, J. Torhorst, P. Schraml, L. Bubendorf, M. M. Mihatsch, H. Moch, G. Sauter (Institute of Pathology), A. Schötzau (Eye Clinic), University of Basel, Switzerland; K. Wilber, Vysis Inc., Downers Grove, IL; J. Kononen, Diomeda Life Sciences Inc., Rockville, MD.
    • Hübscher, Tanja. Affiliations of authors: R. Simon, A. Nocito, T. Hübscher, C. Bucher, J. Torhorst, P. Schraml, L. Bubendorf, M. M. Mihatsch, H. Moch, G. Sauter (Institute of Pathology), A. Schötzau (Eye Clinic), University of Basel, Switzerland; K. Wilber, Vysis Inc., Downers Grove, IL; J. Kononen, Diomeda Life Sciences Inc., Rockville, MD.
    • Bucher, Christoph. Affiliations of authors: R. Simon, A. Nocito, T. Hübscher, C. Bucher, J. Torhorst, P. Schraml, L. Bubendorf, M. M. Mihatsch, H. Moch, G. Sauter (Institute of Pathology), A. Schötzau (Eye Clinic), University of Basel, Switzerland; K. Wilber, Vysis Inc., Downers Grove, IL; J. Kononen, Diomeda Life Sciences Inc., Rockville, MD.
    • Torhorst, Joachim. Affiliations of authors: R. Simon, A. Nocito, T. Hübscher, C. Bucher, J. Torhorst, P. Schraml, L. Bubendorf, M. M. Mihatsch, H. Moch, G. Sauter (Institute of Pathology), A. Schötzau (Eye Clinic), University of Basel, Switzerland; K. Wilber, Vysis Inc., Downers Grove, IL; J. Kononen, Diomeda Life Sciences Inc., Rockville, MD.
    • Schraml, Peter. Affiliations of authors: R. Simon, A. Nocito, T. Hübscher, C. Bucher, J. Torhorst, P. Schraml, L. Bubendorf, M. M. Mihatsch, H. Moch, G. Sauter (Institute of Pathology), A. Schötzau (Eye Clinic), University of Basel, Switzerland; K. Wilber, Vysis Inc., Downers Grove, IL; J. Kononen, Diomeda Life Sciences Inc., Rockville, MD.
    • Bubendorf, Lukas. Affiliations of authors: R. Simon, A. Nocito, T. Hübscher, C. Bucher, J. Torhorst, P. Schraml, L. Bubendorf, M. M. Mihatsch, H. Moch, G. Sauter (Institute of Pathology), A. Schötzau (Eye Clinic), University of Basel, Switzerland; K. Wilber, Vysis Inc., Downers Grove, IL; J. Kononen, Diomeda Life Sciences Inc., Rockville, MD.
    • Mihatsch, Michael M.. Affiliations of authors: R. Simon, A. Nocito, T. Hübscher, C. Bucher, J. Torhorst, P. Schraml, L. Bubendorf, M. M. Mihatsch, H. Moch, G. Sauter (Institute of Pathology), A. Schötzau (Eye Clinic), University of Basel, Switzerland; K. Wilber, Vysis Inc., Downers Grove, IL; J. Kononen, Diomeda Life Sciences Inc., Rockville, MD.
    • Moch, Holger. Affiliations of authors: R. Simon, A. Nocito, T. Hübscher, C. Bucher, J. Torhorst, P. Schraml, L. Bubendorf, M. M. Mihatsch, H. Moch, G. Sauter (Institute of Pathology), A. Schötzau (Eye Clinic), University of Basel, Switzerland; K. Wilber, Vysis Inc., Downers Grove, IL; J. Kononen, Diomeda Life Sciences Inc., Rockville, MD.
    • Wilber, Kim. Affiliations of authors: R. Simon, A. Nocito, T. Hübscher, C. Bucher, J. Torhorst, P. Schraml, L. Bubendorf, M. M. Mihatsch, H. Moch, G. Sauter (Institute of Pathology), A. Schötzau (Eye Clinic), University of Basel, Switzerland; K. Wilber, Vysis Inc., Downers Grove, IL; J. Kononen, Diomeda Life Sciences Inc., Rockville, MD.
    • Schötzau, Andreas. Affiliations of authors: R. Simon, A. Nocito, T. Hübscher, C. Bucher, J. Torhorst, P. Schraml, L. Bubendorf, M. M. Mihatsch, H. Moch, G. Sauter (Institute of Pathology), A. Schötzau (Eye Clinic), University of Basel, Switzerland; K. Wilber, Vysis Inc., Downers Grove, IL; J. Kononen, Diomeda Life Sciences Inc., Rockville, MD.
    • Kononen, Juha. Affiliations of authors: R. Simon, A. Nocito, T. Hübscher, C. Bucher, J. Torhorst, P. Schraml, L. Bubendorf, M. M. Mihatsch, H. Moch, G. Sauter (Institute of Pathology), A. Schötzau (Eye Clinic), University of Basel, Switzerland; K. Wilber, Vysis Inc., Downers Grove, IL; J. Kononen, Diomeda Life Sciences Inc., Rockville, MD.
    • Sauter, Guido. Affiliations of authors: R. Simon, A. Nocito, T. Hübscher, C. Bucher, J. Torhorst, P. Schraml, L. Bubendorf, M. M. Mihatsch, H. Moch, G. Sauter (Institute of Pathology), A. Schötzau (Eye Clinic), University of Basel, Switzerland; K. Wilber, Vysis Inc., Downers Grove, IL; J. Kononen, Diomeda Life Sciences Inc., Rockville, MD.
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Journal of the National Cancer Institute, 2001, vol. 93, no. 15, p. 1141-1146. Oxford University Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:294249
    Summary
    Background: Only 25% of patients with HER-2/neu-positive metastatic breast tumors respond favorably to trastuzamab (Herceptin) treatment. We hypothesized that a high failure rate of patients on trastuzamab could result if some of the metastases were HER-2 negative and these metastases ultimately determine the course of the disease. Methods: We used tissue microarrays (TMAs) containing four samples each from 196 lymph node-negative primary tumors, 196 lymph node-positive primary tumors, and three different lymph node metastases from each lymph node-positive tumor to estimate HER-2 gene amplification by fluorescence in situ hybridization (FISH) and Her-2 protein overexpression by immunohistochemistry (IHC). Results: FISH and IHC analyses gave the same result with respect to HER-2 status for 93.7% of the tissues contained in the TMAs. Tissue samples were, therefore, considered to be HER-2 positive if they were positive for either HER-2 DNA amplification or Her-2 protein expression and HER-2 negative if both FISH and IHC gave a negative result. The HER-2 status of lymph node-positive primary tumors was maintained in the majority of their metastases. For HER-2-positive primary tumors, 77% (95% confidence interval [CI] = 59% to 90%) had entirely HER-2-positive metastases, 6.5% (95% CI = 8% to 21%) had entirely HER-2-negative metastases, and 16.3% (95% CI = 5% to 34%) had a mixture of HER-2-positive and HER-2-negative metastases. For HER-2-negative primary tumors, 95% (95% CI = 88% to 98%) had metastases that were entirely negative for HER-2. Conclusions: Our data suggest that differences in HER-2 expression between primary tumors and their lymph node metastases cannot explain the high fraction of nonresponders to trastuzamab therapy