Polaki Usha S, Gilpin Trey E, Patil Apoorva T, Chiu Emily, Baker Ruth, Liu Peng, Pavletich Tatiana S, Seifi Morteza, Mañán-Mejías Paula M, Morrissey Jordan, Port Jenna, Welch Schwartz Rene, Ong Irene M, El-Rayes Dina, Khalifa Mahmoud A, Hui Pei, Horner Vanessa L, Virumbrales-Muñoz María, Erickson Britt K, Barroilhet Lisa, McGregor Stephanie M, Bresnick Emery H, Matson Daniel R
Department of Pathology and Laboratory Medicine and.
Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, Wisconsin USA.
JCI Insight. 2025 Apr 1;10(9). doi: 10.1172/jci.insight.187073. eCollection 2025 May 8.
BACKGROUNDA priori knowledge of recurrence risk in patients with nonmetastatic (International Federation of Gynecology and Obstetrics [FIGO] stage I) uterine serous carcinoma (USC) would enable a risk-stratified approach to the use of adjuvant chemotherapy. This would greatly reduce treatment-related morbidity and be predicted to improve survival.METHODSGATA2 expression was scored by IHC across a retrospective multiinstitutional cohort of 195 primary USCs. Associations between GATA2 levels and clinicopathologic metrics were evaluated using Student's t test, Fisher's exact test, Kaplan-Meier method, and Cox proportional hazard ratio. Invasion in patient-derived USC cells was assessed by Student's t test. RNA-Seq, anti-GATA2 ChIP-Seq, and confirmatory Western blotting enabled identification of GATA2 targets.RESULTSPatients with FIGO stage I GATA2hi USCs had 100% recurrence-free and 100% cancer-related survival, which was significantly better than patients with GATA2lo USCs. In patients for whom adjuvant chemotherapy was omitted, patients with GATA2hi USC had 100% recurrence-free 5-year survival compared with 60% recurrence-free survival in patients with GATA2lo USC. Depletion of GATA2 in patient-derived USC cells increased invasion in vitro.CONCLUSIONRoutine GATA2 IHC identifies 33% of patients with FIGO stage I USC who have a greatly reduced risk of posthysterectomy USC recurrence. Our results suggest that a GATA2-guided personalized medicine approach could be rapidly implemented in most hospital settings, would reduce treatment-related morbidity, and would likely improve outcomes in patients with USC.FUNDINGNIH grants R01 DK068634, P30 CA014520, S10 OD023526, K08 DK127244, T32 HL007899, the UW-Madison Department of Pathology and Laboratory Medicine, the UW-Madison Centennial Scholars Program, the Diane Lindstrom Foundation, the American Cancer Society, the V Foundation, The Hartwell Foundation, and the UMN Department of Obstetrics, Gynecology, and Women's Health.
背景
对于非转移性（国际妇产科联盟[FIGO] I期）子宫浆液性癌（USC）患者复发风险的先验知识，将有助于采用风险分层方法使用辅助化疗。这将大大降低与治疗相关的发病率，并有望提高生存率。
方法
通过免疫组化（IHC）对195例原发性USC的回顾性多机构队列进行GATA2表达评分。使用学生t检验、Fisher精确检验、Kaplan-Meier方法和Cox比例风险比评估GATA2水平与临床病理指标之间的关联。通过学生t检验评估患者来源的USC细胞中的侵袭情况。RNA测序、抗GATA2染色质免疫沉淀测序（ChIP-Seq）和验证性蛋白质免疫印迹法能够鉴定GATA2靶点。
结果
FIGO I期GATA2高表达（GATA2hi）USC患者的无复发生存率和癌症相关生存率均为100%，显著优于GATA2低表达（GATA2lo）USC患者。在未接受辅助化疗的患者中，GATA2hi USC患者的5年无复发生存率为100%，而GATA2lo USC患者为60%。在患者来源的USC细胞中耗尽GATA2会增加体外侵袭。
结论
常规GATA2 IHC可识别出33%的FIGO I期USC患者，这些患者子宫切除术后USC复发风险大大降低。我们的结果表明，GATA2指导的个性化医疗方法可在大多数医院环境中迅速实施，将降低与治疗相关的发病率，并可能改善USC患者的预后。
资助
美国国立卫生研究院（NIH）资助项目R01 DK068634、P30 CA014520、S10 OD023526、K08 DK127244、T32 HL007899，威斯康星大学麦迪逊分校病理学与检验医学系、威斯康星大学麦迪逊分校百年学者计划、黛安·林德斯特伦基金会、美国癌症协会、V基金会、哈特韦尔基金会，以及明尼苏达大学妇产科与妇女健康系。
