人类表皮生长因子受体2（HER2）在子宫内膜癌中的状态通常是通过免疫组织化学和/或原位杂交法确定的。我们采用了一种新的HER2基因蛋白质分析（GPA）方法，用于同时评估高级别子宫内膜癌中HER2基因扩增和蛋白质表达。我们在180例子宫内膜癌中进行了GPA，其中包括106例浆液性癌、34例肉瘤样癌和40例混合上皮癌。使用2018年乳腺癌HER2指南确定了HER2状态，并检查了HER2肿瘤内异质性（ITH）。收集临床病理特征并与HER2状态相关。浆液性癌中HER2阳性占32％，显著高于肉瘤样癌（5.9％）和混合癌（12.5％）。检测到32％的浆液性癌中的HER2 ITH，显著大于肉瘤样癌（8.8％）和混合上皮癌（10％）。肉瘤样癌患者的总体生存率显著低于浆液性或混合上皮癌患者，但HER2状态在浆液性癌患者中并未导致生存差异。 HER2 GPA可以准确确定子宫内膜癌中HER2的状态，并且是识别HER2异质性的高度有价值的工具。 ©作者（s）2023。 由牛津大学出版社代表美国临床病理学会所发表。版权所有。有关权限，请发送电子邮件至：journals.permissions@oup.com。

Human epidermal growth factor receptor 2 (HER2) status in endometrial cancer is usually determined by immunohistochemistry and/or in situ hybridization. We employed a novel HER2 gene protein assay (GPA) to simultaneously assesses HER2 gene amplification and protein expression in high-grade endometrial cancers.We performed GPA in 180 endometrial cancers, including 106 serous carcinomas, 34 carcinosarcomas, and 40 mixed epithelial carcinomas. HER2 status was determined using the 2018 HER2 guidelines for breast carcinoma, and HER2 intratumoral heterogeneity (ITH) was examined. Clinicopathologic characteristics were collected and correlated with HER2 status.HER2 positivity was noted in 32% of serous carcinomas, significantly higher than in carcinosarcomas (5.9%) and mixed carcinomas (12.5%). HER2 ITH was detected in 32% of serous carcinomas, significantly greater than in carcinosarcomas (8.8%) and mixed carcinomas (10%). Patients with carcinosarcoma had a significantly lower overall survival than patients with serous or mixed epithelial carcinoma, but HER2 status caused no difference in survival in patients with serous carcinoma.HER2 GPA can be used to accurately determine HER2 status in endometrial cancers and is a highly valuable tool for identifying HER2 heterogeneity.© 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.