HER2阳性子宫内膜癌具有独特的分子和免疫特征，与更活跃的免疫微环境和更糟的预后相关。
HER2+ endometrioid endometrial cancer possesses distinct molecular and immunologic features associated with a more active immune microenvironment and worse prognosis.
发表日期：2023 Mar 30
作者：
Shaina F Bruce, Sharon Wu, Jennifer R Ribeiro, Alex Farrell, Matthew J Oberley, Ira Winer, Britt K Erickson, Tenley Klc, Nathaniel L Jones, Premal H Thaker, Matthew A Powell
来源：
GYNECOLOGIC ONCOLOGY
摘要：
HER2在子宫内膜癌（E-EMCA）中通常不进行例行评估，尽管高级别E-EMCA和子宫浆液性癌中经常存在过度表达或扩增。定义HER2+ E-EMCA的特征和生存结果可以揭示哪些受试者子集可能从靶向治疗中受益。Caris Life Sciences数据库中的2927个E-EMCA肿瘤通过下一代测序和全外显子组测序、全转录组测序和免疫组化进行分析，以获取分子和基因组特征，所有实验在CLIA/CAP认证实验室（Caris Life Sciences，Phoenix，AZ）中开展。利用子宫浆液性癌推断出的转录水平截断确定了HER2状态。利用Kaplan-Meier分析确定了HER2状态与患者结果之间的关系。在E-EMCA中，HER2阳性检出率为5.47％。基于HER2状态的分子改变差异在微卫星稳定（MSS）肿瘤中最明显，这些肿瘤显示出增加的TP53突变和等位基因丧失（LOH）以及减少的PTEN和CTNNB1突变。HER2+肿瘤具有增加的免疫检查点基因表达和免疫细胞浸润，特别是在MSS肿瘤中。所有HER2+肿瘤都显示出增加的MAPK通路激活得分（MPAS），HER2+肿瘤患者的总体生存率较差。E-EMCA中的HER2阳性与独特的分子景观相一致，特别是在MSS肿瘤中。HER2+肿瘤还与MAPK通路激活的增加和更活跃的免疫微环境特征相关。这些发现表明，在该患者总体中使用HER2和MAPK的靶向治疗以及免疫治疗可能会有潜在的益处。Copyright © 2023. Published by Elsevier Inc.
HER2 status is not routinely evaluated in endometrioid endometrial cancer (E-EMCA), though it is frequently overexpressed or amplified in high grade E-EMCA and uterine serous carcinoma. Defining characteristics and survival outcomes of HER2+ E-EMCA could reveal subsets of patients who may benefit from targeted therapies.2927 E-EMCA tumors from the Caris Life Sciences database were analyzed by next-generation sequencing and whole exome sequencing, whole transcriptome sequencing, and immunohistochemistry for molecular and genomic features in a CLIA/CAP-certified laboratory (Caris Life Sciences, Phoenix, AZ). HER2 status was determined by transcriptomic cutoff extrapolated from uterine serous carcinoma. The relationship between HER2 status and patient outcomes was determined by Kaplan-Meier analysis.HER2 positivity was detected in 5.47% of E-EMCA. Differences in molecular alterations based on HER2 status were most apparent in microsatellite stable (MSS) tumors, which displayed increased TP53 mutations and loss of heterozygosity (LOH) and decreased PTEN and CTNNB1 mutations. HER2+ tumors had increased immune checkpoint gene expression and immune cell infiltration, particularly among MSS tumors. All HER2+ tumors displayed increased MAPK pathway activation scores (MPAS) and patients with HER2+ tumors experienced worse overall survival.HER2 positivity in E-EMCA corresponds with a unique molecular landscape, particularly in MSS tumors. HER2+ tumors are also associated with increased MAPK pathway activation and exhibit features of a more active immune microenvironment. These findings suggest a potential benefit of HER2 and MAPK targeted therapies as well as immunotherapies in this patient population.Copyright © 2023. Published by Elsevier Inc.