Overexpression of the orphan nuclear receptor NR2F6 is associated with improved survival across molecular subgroups in endometrial cancer patients

INTRODUCTION: NR2F6 (nuclear receptor subfamily 2 group F member 6, also called Ear-2) is known to be an orphan nuclear receptor that has been characterized as an intracellular immune checkpoint in effector T cells and, therefore, may control tumor development and growth. The prognostic impact of NR2F6 in endometrial cancers is evaluated in this study. MATERIALS AND METHODS: Expression analysis of NR2F6 in 142 endometrial cancer patients was performed by immunohistochemistry of primary paraffin‑embedded tumor samples. Staining intensity of positive tumor cells was automatically assessed semi-quantitatively, and results were correlated with clinicopathological characteristics and survival. RESULTS: Forty five of 116 evaluable samples (38.8%) showed an overexpression of NR2F6. This leads to an improvement of the overall survival (OS) and progression-free survival (PFS). In NR2F6-positive patients, the estimated mean OS was 156.9 months (95% confidence interval (CI) 143.1–170.7) compared to 106.2 months in NR2F6-negative patients (95% CI 86.2–126.3; p = 0.022). The estimated PFS differed by 63 months (152 months (95% CI 135.7–168.4) vs. 88.3 months (95% CI 68.5–108.0), p = 0.002). Furthermore, we found significant associations between NR2F6 positivity, MMR status, and PD1 status. A multivariate analysis suggests NR2F6 to be an independent factor influencing the OS (p = 0.03). CONCLUSION: In this study, we could demonstrate that there is a longer progression-free and overall survival for NR2F6-positive patients with endometrial cancer. We conclude that NR2F6 might play an essential role in endometrial cancers. Further studies are required to validate its prognostic impact. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00432-023-04632-2.