Patterns of HER-2/neu amplification and overexpression in primary and metastatic breast cancer

被引:236
作者
Simon, R
Nocito, A
Hübscher, T
Bucher, C
Torhorst, J
Schraml, P
Bubendorf, L
Mihatsch, MM
Moch, H
Wilber, K
Schötzau, A
Kononen, J
Sauter, G
机构
[1] Univ Basel, Inst Pathol, Basel, Switzerland
[2] Univ Basel, Eye Clin, Basel, Switzerland
[3] Vysis Inc, Downers Grove, IL USA
[4] Diomeda Life Sci Inc, Rockville, MD USA
关键词
D O I
10.1093/jnci/93.15.1141
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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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页码:1141 / 1146
页数:6
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