Overexpression of the HER-2 oncogene does not play a role in high-grade osteosarcomas
Overexpression of the HER-2 oncogene does not play a role in high-grade osteosarcomas
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DOI：
10.1016/j.ejca.2003.10.025
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发表时间：
2004-05-01
影响因子：
8.4
通讯作者：
Hogendoorn, PCW
中科院分区：
文献类型：
--
作者：
Anninga, JK;van de Vijver, MJ;Hogendoorn, PCW
我们研究的目的是确定酪氨酸激酶受体HER 2（也称为ErbB 2/Her 2/neu）是否在人骨肉瘤（OS）中过表达。我们研究了15个活检和18个切除标本在mRNA和蛋白水平。通过免疫组织化学（IHC）和定量实时聚合酶链反应（PCR）评估OS标本中的HER 2状态。在中度免疫阳性的情况下，荧光原位杂交（FISH）分析，以确定任何可能的基因扩增。27份样本可用于IHC评估，仅1例显示中度阳性膜染色。其余样本未显示染色或灶性细胞质染色（2份样本）。在中度阳性病例中，FISH分析显示HER-2基因无扩增。也没有HER 2 mRNA的过表达，表明该样品是假阳性免疫染色。所有样品中均存在HER 2 mRNA表达，其水平与乳腺癌细胞系MCF 7中的水平相似，MCF 7不过表达HER 2并用作阴性对照。总之，这项研究表明，HER 2 mRNA或膜HER 2蛋白过表达是不存在的人OS。我们注意到各种不一致的先前发表的研究，关于方法和解释的结果的基础上穷人的方法。因此，我们得出结论，这些先前研究中报告的关于HER 2过表达的阳性数据是不可靠的。我们的研究结果表明，针对HER 2受体的单克隆抗体曲妥珠单抗（赫赛汀（（R）不太可能是OS中的有效治疗药物。（C）2003 Elsevier Ltd.保留所有权利。
The aim of our study was to determine whether or not the tyrosine kinase receptor, HER2 (also known as ErbB2/Her2/neu), is overexpressed in human osteosarcomas (OS). We studied 15 biopsy and 18 resection specimens at the mRNA and protein levels. HER2 status in the OS specimens was assessed by immunohistochemistry (IHC) and quantitative Real-Time Polymerase chain reaction (PCR). In moderately immunopositive cases fluorescent in situ hybridisation (FISH) analysis was used in order to identify any possible gene amplification. 27 samples were evaluable for IHC and only 1 case showed a moderately positive membrane staining. The remaining samples showed no staining or focal cytoplasmic staining (2 samples). In the moderately positive case, FISH analysis showed no HER-2 gene amplification. There was also no overexpression of HER2 mRNA suggesting this sample was a false-positive immunostain. HER2 mRNA expression was present in all samples at a similar level to that in the breast cancer cell line, MCF7, which does not overexpress HER2 and was used as a negative control. In conclusion, this study shows that HER2 mRNA or membranous HER2 protein overexpression is absent in human OS. We noted various inconsistencies in previous published studies, with regard to methodology and the interpretation of the results based on poor methodology. We therefore conclude that the positive data with regard to HER2 overexpression reported in these previous studies is not reliable. Our results suggest that the monoclonal antibody trastuzumab (Herceptin((R))), directed against the HER2-receptor, is not likely to be an effective therapeutic agent in OS. (C) 2003 Elsevier Ltd. All rights reserved.