Targos - A Discovery Life Sciences Company, Germaniastraße 7, 34119, Kassel, Germany.
Institute of Pathology Nordhessen, Germaniastraße 7, 34119, Kassel, Germany.
Virchows Arch. 2022 Nov;481(5):685-694. doi: 10.1007/s00428-022-03378-5. Epub 2022 Aug 16.
Performance of the new CE-IVD-marked HercepTest™ mAb pharmDx (Dako Omnis) assay (HercepTest (mAb)) was compared against the PATHWAY® anti-HER-2/neu (4B5) (PATHWAY 4B5) assay using 119 pre-selected breast cancer samples covering the entire range of HER2 immunohistochemistry (IHC) expression scores (0, 1 + , 2 + , 3 +). The sensitivity and specificity of both assays were assessed based on consensus IHC scores and amplification status, as determined by fluorescence in situ hybridization (FISH) according to 2018 ASCO/CAP testing guidelines. There was a high concordance between results from the HercepTest (mAb) and PATHWAY 4B5 assays for HER2-negative (IHC 0, 1 + , 2 + and FISH negative) and HER2-positive (IHC 3 + , 2 + and FISH positive) breast carcinomas (98.2%). Regarding individual IHC scores, complete agreement was achieved in 69.7% (83/119) of cases, and all but one of the discordant cases were due to higher HER2-status scoring using the HercepTest (mAb). Thus, more tumors were overscored as IHC 2 + by HercepTest (mAb) (27 versus 15) as evidenced by their lower FISH positivity rate (48.1% versus 80%). However, two amplified tumors identified as IHC 2 + by HercepTest (mAb) were missed by PATHWAY 4B5 (IHC 1 +). Four additional cases identified as IHC 2 + by HercepTest (mAb), with FISH ratio < 2 but elevated gene counts (≥ 4 to < 6), were recorded negative by PATHWAY 4B5. The HercepTest (mAb) detects HER2 expression with higher sensitivity in tumors with gene amplification (ISH group 1) and increased gene counts (ISH group 4) as well as in HER2-low tumors (HER2 IHC2 + /FISH negative or IHC 1 +). Future studies will demonstrate whether this translates into improved patient selection especially for new HER2-directed therapies.
新的 CE-IVD 标记的 HercepTest™ mAb pharmDx（Dako Omnis）检测（HercepTest（mAb））的性能与 PATHWAY®抗 HER-2/neu（4B5）（PATHWAY 4B5）检测进行了比较，使用了 119 个预先选择的涵盖整个 HER2 免疫组化（IHC）表达评分范围的乳腺癌样本（0、1+、2+、3+）。根据 2018 年 ASCO/CAP 检测指南，根据共识 IHC 评分和扩增状态，使用荧光原位杂交（FISH）评估两种检测方法的敏感性和特异性。在 HER2 阴性（IHC 0、1+、2+和 FISH 阴性）和 HER2 阳性（IHC 3+、2+和 FISH 阳性）乳腺癌中，HercepTest（mAb）和 PATHWAY 4B5 检测的结果高度一致（98.2%）。关于个别 IHC 评分，在 69.7%（83/119）的病例中达到完全一致，所有不一致的病例均归因于使用 HercepTest（mAb）进行更高的 HER2 状态评分。因此，更多的肿瘤被过度评分为 IHC 2+（27 比 15），这表明它们的 FISH 阳性率较低（48.1%比 80%）。然而，两个被 HercepTest（mAb）鉴定为 IHC 2+的扩增肿瘤被 PATHWAY 4B5 漏检（IHC 1+）。另外四个被 HercepTest（mAb）鉴定为 IHC 2+的病例，FISH 比值<2 但基因计数升高（≥4 至<6），被 PATHWAY 4B5 记录为阴性。HercepTest（mAb）在基因扩增（ISH 组 1）和基因计数增加（ISH 组 4）的肿瘤以及 HER2 低肿瘤（HER2 IHC2+ / FISH 阴性或 IHC 1+）中，具有更高的 HER2 表达检测敏感性。未来的研究将表明这是否转化为对新的 HER2 靶向治疗的患者选择的改善。
