© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 15, 1141-1146,
August 1, 2001
© 2001 Oxford University Press
REPORT |
Patterns of HER-2/neu Amplification and Overexpression in Primary and Metastatic Breast Cancer
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.
Correspondence to: Guido Sauter, M.D., Institute of Pathology, University Hospital, Schoenbeinstrasse 40, 4003 Basel, Switzerland (e-mail: Guido.Sauter{at}unibas.ch).
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.
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