Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Pathology, Barts Health NHS Trust, London, UK.
Histopathology. 2021 Oct;79(4):533-543. doi: 10.1111/his.14381. Epub 2021 Jul 5.
Human epidermal growth factor receptor 2 (HER2) amplification in endometrial cancer (EC) is almost completely confined to the p53-abnormal (p53abn) molecular subtype and independent of histological subtype. HER2 testing should therefore be molecular subtype-directed. However, the most optimal approach for HER2 testing in EC has not been fully established. Therefore, we developed an EC-specific HER2 immunohistochemistry (IHC) scoring method and evaluated its reproducibility and performance to establish an optimal diagnostic HER2 testing algorithm for p53abn EC.
HER2 IHC slides of 78 p53abn EC were scored by six gynaecopathologists according to predefined EC-specific IHC scoring criteria. Interobserver agreement was calculated using Fleiss' kappa and the first-order agreement coefficient (AC1). The consensus IHC score was compared with HER2 dual in-situ hybridisation (DISH) results. Sensitivity and specificity were calculated. A substantial interobserver agreement was found using three- or two-tiered scoring [κ = 0.675, 95% confidence interval (CI) = 0.633-0.717; AC1 = 0.723, 95% CI = 0.643-0.804 and κ = 0.771, 95% CI = 0.714-0.828; AC1 = 0.774, 95% CI = 0.684-0.865, respectively]. Sensitivity and specificity for the identification of HER2-positive EC was 100 and 97%, respectively, using a HER2 testing algorithm that recommends DISH in all cases with moderate membranous staining in >10% of the tumour (IHC+). Performing DISH on all IHC-2+ and -3+ cases yields a sensitivity and specificity of 100%.
Our EC-specific HER2 IHC scoring method is reproducible. A screening strategy based on IHC scoring on all cases with subsequent DISH testing on IHC-2+/-3+ cases has perfect test accuracy for identifying HER2-positive EC.
人类表皮生长因子受体 2（HER2）在子宫内膜癌（EC）中的扩增几乎完全局限于 p53 异常（p53abn）分子亚型，与组织学亚型无关。因此，HER2 检测应针对分子亚型。然而，尚未完全确定 EC 中 HER2 检测的最佳方法。因此，我们开发了一种 EC 特异性 HER2 免疫组织化学（IHC）评分方法，并评估了其重复性和性能，以建立用于 p53abn EC 的最佳诊断 HER2 检测算法。
根据预先设定的 EC 特异性 IHC 评分标准，由六名妇科病理学家对 78 例 p53abn EC 的 HER2 IHC 切片进行评分。使用 Fleiss'kappa 和一阶一致性系数（AC1）计算观察者间一致性。比较共识 IHC 评分与 HER2 双重原位杂交（DISH）结果。计算敏感性和特异性。使用三分层或两分层评分发现了实质性的观察者间一致性[κ=0.675，95%置信区间（CI）=0.633-0.717；AC1=0.723，95%CI=0.643-0.804 和 κ=0.771，95%CI=0.714-0.828；AC1=0.774，95%CI=0.684-0.865]。使用建议在所有中度膜染色>10%的肿瘤（IHC+）的情况下进行 DISH 的 HER2 检测算法，识别 HER2 阳性 EC 的敏感性和特异性分别为 100%和 97%。对所有 IHC-2+和-3+病例进行 DISH 检测的敏感性和特异性为 100%。
我们的 EC 特异性 HER2 IHC 评分方法具有可重复性。基于所有病例的 IHC 评分，随后对 IHC-2+/ -3+病例进行 DISH 检测的筛查策略，对于识别 HER2 阳性 EC 具有完美的测试准确性。
