# Loss of GATA2 promotes invasion and predicts cancer recurrence and survival in uterine serous carcinoma

## TL;DR

Low GATA2 expression in early-stage uterine serous carcinoma is linked to higher cancer recurrence and worse survival, suggesting it could guide personalized treatment decisions.

## Contribution

Loss of GATA2 expression is shown to promote invasion and predict recurrence and survival in uterine serous carcinoma.

## Key findings

- Patients with high GATA2 expression had 100% recurrence-free and cancer-related survival, compared to lower survival in low GATA2 patients.
- GATA2 depletion in USC cells increased invasion in vitro.
- Routine GATA2 IHC identifies a subset of stage I patients with reduced recurrence risk.

## Abstract

A 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.

GATA2 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.

Patients 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.

Routine 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.

NIH 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.

Loss of GATA2 expression leads to uterine serous carcinoma invasion and metastasis. Routine GATA2 immunohistochemistry predicts cancer recurrence and patient survival in FIGO stage I uterine serous carcinoma.