HER2 immunohistochemistry in endometrial and ovarian clear cell carcinoma: discordance between antibodies and with in-situ hybridisation
HER2 immunohistochemistry in endometrial and ovarian clear cell carcinoma: discordance between antibodies and with in-situ hybridisation
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DOI：
10.1111/his.13704
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发表时间：
2018-11-01
期刊：
影响因子：
6.4
通讯作者：
Hollema, Harry
中科院分区：
文献类型：
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作者：
Koopman, Timco;van der Vegt, Bert;Hollema, Harry
目的方法和结果抗HER 2治疗对HER 2阳性的子宫内膜和卵巢透明细胞癌（CCC）患者是有益的。我们使用三种不同的抗体通过免疫组织化学（IHC）研究了HER 2的过度表达，包括原位杂交扩增（ISH）的一致性。IHC和ISH在101个肿瘤的组织微阵列上进行：58个子宫内膜纯CCC，19个子宫内膜混合癌CCC组件和24个卵巢纯CCC。使用SP3、4 B5和HercepTest抗体进行IHC，并由两名独立观察员进行评分。使用双色银ISH进行ISH。使用IHC，SP3/4 B5之间的一致性较差（61.4%），SP3/HercepTest之间的一致性较差（68.3%），4 B5/HercepTest之间的一致性合理（75.2%）。所有抗体的观察者间一致性基本上达到几乎完美（SP3：线性加权= 0.89，4 B5：= 0.90，HercepTest：= 0.76）。ISH检测的HER 2阳性率为17.8%（子宫内膜单纯CCC：24.1%，子宫内膜混合型CCC：0%，卵巢单纯CCC：16.7%）。IHC/ISH一致性较差，所有三种IHC抗体的假阴性率均较高：灵敏度（38.9-50.0%）和阳性预测值（PPV）（37.5-58.3%）较差;特异性（81.9-94.0%）和阴性预测值（NPV）（87.1-88.3%）合理。当排除2+例时，敏感性下降（26.7-43.8%），但PPV（80.0-87.5%）和特异性（98.6-98.7%）提高。因此，没有单一抗体可以被认为是确定CCC中HER 2状态的决定性抗体。基于这些结果，可以解释其他研究中使用的不同HER 2检测方法缺乏预测价值。
AimsMethods and resultsTreatment with anti-HER2 therapy could be beneficial for patients with HER2-positive endometrial and ovarian clear cell carcinoma (CCC). We studied HER2 overexpression by immunohistochemistry (IHC) using three different antibodies, including concordance with amplification by in-situ hybridisation (ISH).IHC and ISH were performed on tissue microarrays of 101 tumours: 58 endometrial pure CCC, 19 endometrial mixed carcinomas with a CCC component and 24 ovarian pure CCC. IHC was performed using SP3, 4B5 and HercepTest antibodies, and was scored by two independent observers. ISH was performed using dual-colour silver ISH. Using IHC, agreement was poor between SP3/4B5 (61.4%), poor between SP3/HercepTest (68.3%) and reasonable between 4B5/HercepTest (75.2%). Interobserver agreement was substantial to almost perfect for all antibodies (SP3: linear weighted = 0.89, 4B5: = 0.90, HercepTest: = 0.76). HER2-positivity by ISH was 17.8% (endometrial pure CCC: 24.1%, endometrial mixed: 0%, ovarian pure CCC: 16.7%). IHC/ISH concordance was poor, with a high false-negative rate of all three IHC antibodies: sensitivity (38.9-50.0%) and positive predictive value (PPV) (37.5-58.3%) were poor; specificity (81.9-94.0%) and negative predictive value (NPV) (87.1-88.3%) were reasonable. When excluding 2+ cases, sensitivity declined (26.7-43.8%) but PPV (80.0-87.5%) and specificity (98.6-98.7%) improved.ConclusionsIn ovarian and endometrial CCC, there is considerable difference in HER2 overexpression by different IHC antibodies and marked discordance with ISH. As such, no single antibody can be considered conclusive for determining HER2 status in CCC. Based on these results, the lack of predictive value of different HER2 testing methods, as used in other studies, could be explained.