A modified Trastuzumab antibody for the immunohistochemical detection of HER-2 overexpression in breast cancer.
A modified Trastuzumab antibody for the immunohistochemical detection of HER-2 overexpression in breast cancer.
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DOI：
10.1038/sj.bjc.6602507
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发表时间：
2005-04-11
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
HER-2的免疫组织化学测定用于识别曲妥珠单抗治疗的晚期乳腺癌候选患者既不准确也不完全可靠，可能是因为目前的试剂都不能检测曲妥珠单抗的特异性抗原位点靶标。为了避免这个问题，我们将曲妥珠单抗的NH 2基团与生物素结合，并将获得的化合物（命名为BiotHER）直接加入组织切片中。辣根过氧化物酶结合的链霉亲和素揭示了生物素标记。在164例乳腺癌标本上检测了BiotHER免疫染色对HER-2扩增的特异性和敏感性。BiotHER染色在所有标本的12%和49%的基因扩增标本的肿瘤细胞膜上检测到，而在非扩增肿瘤中则不存在。在54例接受曲妥珠单抗联合化疗的HER-2扩增晚期乳腺癌患者中分析了BiotHER状态对临床结局的预测性。在50%的HER-2扩增肿瘤中检测到的BiotHER染色是临床结果的独立预测因子。事实上，BiotHER阳性与肿瘤缓解的可能性增加以及肿瘤进展和死亡风险降低独立相关。因此，生物素化曲妥珠单抗可用于乳腺癌HER-2过表达的免疫组化检测，并有可能识别可能从曲妥珠单抗治疗中获益的患者。
The immunohistochemical determination of HER-2 to identify patients with advanced breast cancer candidates for Trastuzumab treatment proved neither accurate nor fully reliable, possibly because none of the current reagents detects the specific antigenic site target of Trastuzumab. To circumvent this problem, we conjugated the NH2 groups of Trastuzumab with biotin, and the compound obtained, designated BiotHER, was added directly to tissue sections. Biotin-labelling was revealed with horseradish peroxidase-conjugated streptavidin. Specificity and sensitivity of BiotHER immunostaining with respect to HER-2 amplification were tested on 164 breast carcinoma samples. BiotHER staining was detected on the tumour cell membrane of 12% of all specimens and in 49% specimens with gene amplification, while absent in nonamplified tumours. Predictivity of BiotHER status with respect to the clinical outcome was analysed in 54 patients with HER-2 amplified advanced breast cancer treated with Trastuzumab plus chemotherapy. BiotHER staining, detected in 50% of tumours with HER-2 amplification, was an independent predictor of clinical outcome. In fact, BiotHER positivity was independently associated with increased likelihood of tumour response and reduced risk of tumour progression and death. Biotinylated Trastuzumab can thus be used for immunohistochemical detection of HER-2 overexpression in breast cancer, and has the potential to identify patients likely to benefit from Trastuzumab treatment.
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通讯作者：
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