Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
Department of Community Health, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
Indian J Pathol Microbiol. 2021 Oct-Dec;64(4):677-682. doi: 10.4103/IJPM.IJPM_983_20.
Human epidermal growth factor receptor 2 (HER2) over-expression in breast cancer is associated with aggressive tumor behavior and predicts response to targeted therapy. Accurate HER2 result is paramount for optimal patient management. However, routine HER2 immunohistochemistry (IHC) testing are subjected to intra- and inter-laboratory variability.
This study aims to determine inter-laboratory variation in HER2 IHC testing through a slide-exchange program between five main reference laboratories.
A total of 20 breast carcinoma cases with different known HER2 expression and gene status were selected by the central laboratory in five testing rounds. Three unstained tissue sections from each case were sent to participating laboratories, which immunostained and interpreted the HER2 immunohistochemistry result. One of the stained slides was sent to one designated participating laboratory for evaluation. Results were analyzed by the central laboratory.
A complete concordance was achieved in six IHC-positive and six IHC-negative cases, its gene status of which was confirmed by in-situ-hybridization (ISH) study. The discordant results were observed in six equivocal cases, one negative case and one positive case with a concordance rate of 50-88.3%. Interestingly, the negative discordant case actually displays tumor heterogeneity. Good inter-observer agreement was achieved for all participating laboratories (k = 0.713-1.0).
Standardization of HER2 testing method is important to achieve optimum inter-laboratory concordance. Discordant results were seen mainly in equivocal cases. Intra-tumoral heterogeneity may impact the final HER2 IHC scoring. The continuous quality evaluation is therefore paramount to achieve reliable HER2 results.
乳腺癌中人类表皮生长因子受体 2（HER2）过表达与侵袭性肿瘤行为相关，并预测对靶向治疗的反应。准确的 HER2 结果对于患者的最佳管理至关重要。然而，常规的 HER2 免疫组化（IHC）检测存在实验室内和实验室间的变异性。
本研究旨在通过五个主要参考实验室之间的幻灯片交换计划，确定 HER2 IHC 检测的实验室间变异性。
由中央实验室在五个检测轮次中选择了总共 20 例具有不同已知 HER2 表达和基因状态的乳腺癌病例。每个病例的三个未染色组织切片被发送至参与实验室，这些实验室对 HER2 免疫组化结果进行免疫染色和解释。其中一个染色幻灯片被发送至一个指定的参与实验室进行评估。结果由中央实验室进行分析。
在六个 IHC 阳性和六个 IHC 阴性病例中实现了完全一致，其基因状态通过原位杂交（ISH）研究得到了证实。在六个不确定的病例、一个阴性病例和一个阳性病例中观察到了不一致的结果，其符合率为 50-88.3%。有趣的是，实际上，阴性不一致病例显示出肿瘤异质性。所有参与实验室均实现了良好的观察者间一致性（k = 0.713-1.0）。
HER2 检测方法的标准化对于实现最佳实验室间一致性非常重要。不一致的结果主要见于不确定的病例。肿瘤内异质性可能会影响最终的 HER2 IHC 评分。因此，持续的质量评估对于获得可靠的 HER2 结果至关重要。
