我们评估了HER2免疫组化得分在富含HER2低表达乳腺癌队列中的观察者间和抗体间重现性。共有114个乳腺癌标本使用HercepTest（Agilent Dako）和PATHWAY反-HER2（4B5）（Ventana）抗体试剂进行染色，并由6位乳腺病理学家根据当前HER2指南独立评分。通过Cohen κ分析评估一致性水平。尽管两种抗体的观察者间一致性达到了显著一致性，但HercepTest的平均一致率显著高于4B5克隆的一致率（74.3%对65.1%；P = 。002）。两种抗体之间的总体抗体一致性率为57.8%。通过HercepTest和4B5分别在44.7%和45.6%的病例中实现了完全的观察者一致性。绝对一致率从HER2 0-1+（78.1% HercepTest和72.2% 4B5；中等一致性）增加到HER2 2-3+（91.9% HercepTest和86.3% 4B5；几乎完全一致性）。我们的结果表明，在评估HER2免疫组化时存在明显的观察者间和抗体间变异，特别是在得分为0-1+的病例中，尽管乳腺专科病理学家对HER2低概念有所认知后，表现得到了明显改善。需要更准确和可重复的方法来选择可能从新获批准的HER2靶向药物在HER2低表达乳腺癌中受益的患者。© 作者(们) 2023。由牛津大学出版社代表美国临床病理学会出版。保留所有权利。有关权限，请发送电子邮件至：journals.permissions@oup.com。

We assessed the interobserver and interantibody reproducibility of HER2 immunohistochemical scoring in an enriched HER2-low-expressing breast cancer cohort.A total of 114 breast cancer specimens were stained by HercepTest (Agilent Dako) and PATHWAY anti-HER2 (4B5) (Ventana) antibody assays and scored by 6 breast pathologists independently using current HER2 guidelines. Level of agreement was evaluated by Cohen κ analysis.Although the interobserver agreement rate for both antibodies achieved substantial agreement, the average rate of agreement for HercepTest was significantly higher than that for the 4B5 clone (74.3% vs 65.1%; P = .002). The overall interantibody agreement rate between the 2 antibodies was 57.8%. Complete interobserver concordance was achieved in 44.7% of cases by HercepTest and 45.6% of cases by 4B5. Absolute agreement rates increased from HER2 0-1+ cases (78.1% by HercepTest and 72.2% by 4B5; moderate agreement) to 2-3+ cases (91.9% by HercepTest and 86.3% by 4B5; almost perfect agreement).Our results demonstrated notable interobserver and interantibody variation on evaluating HER2 immunohistochemistry, especially in cases with scores of 0-1+, although the performance was much more improved among breast-specialized pathologists with the awareness of HER2-low concept. More accurate and reproducible methods are needed for selecting patients who may benefit from the newly approved HER2-targeting agent on HER2-low breast cancers.© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.