Koopman Timco, Louwen Maarten, Hage Mariska, Smits Maria M, Imholz Alex L T
From the Departments of Medical Oncology and.
Pathology, Deventer Hospital, Deventer, the Netherlands.
Am J Clin Pathol. 2015 Feb;143(2):257-64. doi: 10.1309/AJCPCX69HGDDGYCQ.
The human epidermal growth factor receptor 2 (HER2) oncogene shows overexpression in 15% to 30% of gastroesophageal adenocarcinomas. Targeted anti-HER2 therapy with trastuzumab has been recently validated in advanced gastric and gastroesophageal junction cancer treatment. A standardized modified scoring system was recently introduced for gastroesophageal HER2 scoring. We aimed to validate this scoring system, including an analysis of interobserver variability of immunohistochemistry (IHC) scoring.
In total, 323 patients with histologically confirmed invasive gastric or esophageal adenocarcinoma were examined for HER2 by IHC and chromogenic in situ hybridization (CISH). IHC 3 + or IHC 2 +/CISH positive tumors were considered HER2 positive. Interobserver variability on IHC scoring using the currently standard modified HER2 scoring system was determined among three clinical pathologists. Clinicopathologic characteristics were retrospectively retrieved from the patient records.
HER2 positivity was found in 50 (15.5%) of 323 patients. Interobserver agreement on IHC scoring was high (κ = 0.78). Most disagreement was found in diffuse or mixed tumor types and in weak to moderate stained samples (IHC 2 +). The HER2 IHC scoring system is sensitive in differentiating HER2 status before ISH.
The currently used standardized HER2 scoring system is an excellent, clinically applicable method to establish HER2 status in appropriately educated and trained pathologists.
人表皮生长因子受体2（HER2）癌基因在15%至30%的胃食管腺癌中呈过表达。曲妥珠单抗靶向抗HER2治疗最近已在晚期胃癌和胃食管交界癌治疗中得到验证。最近引入了一种标准化的改良评分系统用于胃食管HER2评分。我们旨在验证该评分系统，包括分析免疫组织化学（IHC）评分的观察者间变异性。
总共323例经组织学确诊的浸润性胃癌或食管腺癌患者接受了IHC和显色原位杂交（CISH）检测HER2。IHC 3 +或IHC 2 +/CISH阳性肿瘤被视为HER2阳性。在三名临床病理学家之间确定使用当前标准改良HER2评分系统进行IHC评分的观察者间变异性。从患者记录中回顾性检索临床病理特征。
323例患者中有50例（15.5%）HER2呈阳性。观察者间在IHC评分上的一致性较高（κ = 0.78）。大多数分歧出现在弥漫性或混合型肿瘤类型以及弱阳性至中等染色的样本（IHC 2 +）中。HER2 IHC评分系统在ISH之前区分HER2状态方面具有敏感性。
当前使用的标准化HER2评分系统是一种优秀的、临床适用的方法，可用于在经过适当教育和培训的病理学家中确定HER2状态。
