Lebeau A, Deimling D, Kaltz C, Sendelhofert A, Iff A, Luthardt B, Untch M, Löhrs U
Pathologisches Institut and Klinik für Frauenheilkunde und Geburtshilfe Klinikum-GroBhadern, Ludwig-Maximilians-Universität, München, Germany.
J Clin Oncol. 2001 Jan 15;19(2):354-63. doi: 10.1200/JCO.2001.19.2.354.
The objective of our study was to compare the methods used in the literature to analyze HER-2/neu status on archival breast cancer tissue. Therefore, a series of antibodies was evaluated to assess their immunohistochemical (IHC) sensitivity in correlation to gene amplification determined by fluorescence in situ hybridization (FISH).
HER-2/neu overexpression was studied on paraffin sections of 85 invasive breast cancers using a panel of five monoclonal (9G6, 3B5, CB11, TAB250, GSF-HER2) and two polyclonal antibodies (A8010, A0485) in addition to the HercepTest (DAKO, Glostrup, Denmark). HER-2/neu gene amplification was determined by FISH using a dual-color probe (PathVysion; Vysis, Stuttgart-Fasanenhof, Germany).
HER-2/neu overexpression was demonstrated in 26% (9G6, TAB250, GSF-HER2), 27% (3B5, CB11), 33% (A8010) and 42% (A0485, HercepTest) of the tumors. FISH on paraffin sections identified gene amplification in 28% of the tumors. Strongly positive IHC results (3+) were always associated with gene amplification. Among the 16 tumors presented with weakly positive IHC results (2+) using the HercepTest, 12 (75%) lacked gene amplification.
The comparison of IHC and FISH demonstrated an excellent correlation of high-level HER-2/neu overexpression (3+) with gene amplification; ie, FISH does not provide further information in these tumors. However, weakly positive IHC results (2+) obtained with the HercepTest share only a minor association with gene amplification.
我们研究的目的是比较文献中用于分析存档乳腺癌组织中HER-2/neu状态的方法。因此，评估了一系列抗体，以评估其免疫组织化学（IHC）敏感性与通过荧光原位杂交（FISH）确定的基因扩增之间的相关性。
除了HercepTest（丹麦格罗斯特鲁普的达科公司）外，还使用一组五种单克隆抗体（9G6、3B5、CB11、TAB250、GSF-HER2）和两种多克隆抗体（A8010、A0485）对85例浸润性乳腺癌的石蜡切片进行HER-2/neu过表达研究。使用双色探针（PathVysion；德国斯图加特-法萨嫩霍夫的Vysis公司）通过FISH确定HER-2/neu基因扩增。
在26%（9G6、TAB250、GSF-HER2）、27%（3B5、CB11）、33%（A8010）和42%（A0485、HercepTest）的肿瘤中检测到HER-2/neu过表达。石蜡切片的FISH检测发现28%的肿瘤存在基因扩增。IHC强阳性结果（3+）总是与基因扩增相关。在使用HercepTest检测为IHC弱阳性结果（2+）的16例肿瘤中，12例（75%）没有基因扩增。
IHC和FISH的比较表明，高水平HER-2/neu过表达（3+）与基因扩增具有良好的相关性；即，FISH在这些肿瘤中无法提供更多信息。然而，使用HercepTest获得的IHC弱阳性结果（2+）与基因扩增仅有较小的相关性。
