Prognostic Value of p53 Status in Endometrial Cancer: Real-World Evidence from a Tertiary Center

Background: p53 immunohistochemistry is widely used as a surrogate marker for molecular classification in endometrial cancer and is generally associated with aggressive tumor behavior. However, its independent prognostic value in real-world clinical settings remains uncertain. Methods: This retrospective cohort study included patients with histologically confirmed endometrial cancer treated at a tertiary center between 2015 and 2023. Patients with available p53 immunohistochemical results were classified as p53 wild-type or p53-abnormal status. Clinicopathologic characteristics were compared between groups. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), were analyzed using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards models were used to identify independent prognostic factors. Sensitivity analyses were performed to assess the impact of treatment-related variables. Results: A total of 132 patients were included. p53-abnormal tumors were associated with older age, high-grade non-endometrioid histology, and more frequent use of adjuvant therapy. In Kaplan-Meier analysis, p53-abnormal status was associated with poorer OS (5-year OS: 54.8% vs. 77.1%, p = 0.029), with a similar trend observed for PFS. However, in multivariable analysis, p53 status was not independently associated with survival. Instead, advanced stage and residual disease remained significant prognostic factors. Sensitivity analyses incorporating treatment-related variables yielded consistent results, confirming the lack of independent prognostic impact of p53. Conclusions: Although p53-abnormal status was associated with adverse clinicopathologic features and worse unadjusted survival, it was not an independent prognostic factor after adjustment. These findings suggest that the prognostic impact of p53 is context-dependent and largely mediated by established clinical factors, particularly tumor burden. Integrated clinicopathologic and molecular assessment remains essential for accurate risk stratification in endometrial cancer.