Patterns of HER-2/neu amplification and overexpression in primary and metastatic breast cancer
Patterns of HER-2/neu amplification and overexpression in primary and metastatic breast cancer
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DOI：
10.1093/jnci/93.15.1141
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发表时间：
2001-08-01
期刊：
影响因子：
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通讯作者：
Sauter, G
中科院分区：
文献类型：
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作者：
Simon, R;Nocito, A;Sauter, G
背景：只有25%的HER-2/neu阳性转移性乳腺肿瘤患者对曲妥珠单抗（赫赛汀）治疗反应良好。我们假设，如果一些转移瘤是HER-2阴性的，并且这些转移瘤最终决定了疾病的进程，那么使用曲妥珠单抗的患者的高失败率可能会导致。方法：我们使用组织微阵列（TMA），其包含来自196个淋巴结阴性原发性肿瘤、196个淋巴结阳性原发性肿瘤和来自每个淋巴结阳性肿瘤的三个不同淋巴结转移瘤的各四个样本，通过荧光原位杂交（FISH）和免疫组织化学（IHC）来估计HER-2基因扩增和HER-2蛋白过表达。结果：FISH和IHC分析对于TMA中93.7%的组织的HER-2状态给出了相同的结果。因此，如果组织样本HER-2 DNA扩增或HER-2蛋白表达阳性，则认为它们是HER-2阳性的，如果FISH和IHC均给出阴性结果，则认为它们是HER-2阴性的。淋巴结阳性原发肿瘤的HER-2状态在大多数转移灶中得以维持。对于HER-2阳性原发性肿瘤，77%（95%置信区间[CI] = 59%-90%）完全HER-2阳性转移，6.5%（95% CI = 8%-21%）完全HER-2阴性转移，16.3%（95% CI = 5%-34%）混合HER-2阳性和HER-2阴性转移。对于HER-2阴性的原发肿瘤，95%（95%CI = 88%-98%）的转移灶HER-2完全阴性。结论：原发肿瘤和淋巴结转移灶之间HER-2表达的差异不能解释高比例的曲妥珠单抗治疗无效者。
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 fluorescencein situhybridization (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.