Loss of GATA2 promotes invasion and predicts cancer recurrence and survival in uterine serous carcinoma.
| Publication Type | Academic Article |
| Authors | Polaki U, Gilpin T, Patil A, Chiu E, Baker R, Liu P, Pavletich T, Seifi M, Mañán-Mejías P, Morrissey J, Port J, Welch Schwartz R, Ong I, El-Rayes D, Khalifa M, Hui P, Horner V, Virumbrales-Muñoz M, Erickson B, Barroilhet L, McGregor S, Bresnick E, Matson D |
| Journal | JCI Insight |
| Volume | 10 |
| Issue | 9 |
| Date Published | 04/01/2025 |
| ISSN | 2379-3708 |
| Keywords | GATA2 Transcription Factor, Uterine Neoplasms, Neoplasm Recurrence, Local, Cystadenocarcinoma, Serous |
| Abstract | 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. |
| DOI | 10.1172/jci.insight.187073 |
| PubMed ID | 40168074 |
| PubMed Central ID | PMC12128953 |