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HER2基因蛋白检测:评估子宫内膜癌中HER2状态及肿瘤内异质性的可靠工具

HER2 Gene Protein Assay: A Robust Tool for Evaluating HER2 Status and Intratumoral Heterogeneity in Endometrial Cancers

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影响因子:1.9
分区:医学4区 / 病理学3区
发表日期:2023 May 02
作者: Saba Shafi, Hiroaki Nitta, Manan Shah, Bindu Challa, Anil V Parwani, Zaibo Li
DOI: 10.1093/ajcp/aqac179

摘要

人表皮生长因子受体2(HER2)在子宫内膜癌中的状态通常通过免疫组化和/或原位杂交法确定。我们采用一种新型HER2基因蛋白检测(GPA)同时评估高等级子宫内膜癌中的HER2基因扩增和蛋白表达。我们在180例子宫内膜癌中进行了GPA检测,包括106例浆液性癌、34例癌肉瘤和40例混合上皮癌。根据2018年乳腺癌HER2指南确定HER2状态,并检查HER2的肿瘤内异质性(ITH)。收集临床病理特征并与HER2状态进行相关分析。HER2阳性在浆液性癌中观察到的比例为32%,明显高于癌肉瘤(5.9%)和混合癌(12.5%)。HER2肿瘤内异质性在浆液性癌中检测到的比例为32%,明显高于癌肉瘤(8.8%)和混合癌(10%)。患癌肉瘤的患者总体生存明显低于浆液性或混合上皮癌患者,但HER2状态对浆液性癌患者的生存无显著影响。HER2 GPA可以准确判定子宫内膜癌中的HER2状态,是识别HER2异质性的极具价值的工具。

Abstract

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.