Impact of p53 status on recurrence patterns and oncologic outcomes in non-invasive high-grade endometrial cancer.

OBJECTIVE: This retrospective study evaluated the impact of p53-abnormal (p53abn) status on recurrence patterns and outcomes among patients with non-invasive, high-grade endometrial cancer (EC) treated at the Brazilian National Cancer Institute (INCA) between 2010 and 2025. METHODS: Eligible patients had high-grade histologies-including endometrioid grade 3 (ECG3), serous (USC), clear cell (CC), carcinosarcoma (CS), mixed, or undifferentiated tumors-without myometrial invasion. Clinical, surgical, and pathological characteristics, as well as recurrence and survival data, were reviewed. Immunohistochemical analysis of p53 expression was performed, and p53 status was correlated with clinical outcomes, particularly recurrence rate. RESULTS: Fifty-nine patients met the inclusion criteria, with a mean age of 65 years. Most underwent total hysterectomy with or without bilateral salpingo-oophorectomy (59.3%); 40.7% also received lymphadenectomy or omentectomy. Histologic distribution was mainly endometrioid (39.0%) and serous (39.0%). Forty-six (78%) and 13 (22%) had p53 abnormal and normal tumors. Seven patients (11.9%) received chemotherapy and 15 (25.4%) received radiotherapy. Three patients had already disease outside uterus. Among 56 patients with FIGO stage IC disease, recurrence occurred in 16.1%, predominantly at extra-pelvic sites (33.3% abdominal, 22.2% distant). Five-year recurrence was 23.2% for p53abn tumors versus 0% for wild-type, and 12.5% of patients died-mostly within the p53abn subgroup. CONCLUSION: The findings suggest that even in non-invasive high-grade EC, p53 abnormalities confer higher recurrence risk and poorer outcomes, while wild-type tumors show excellent prognosis. These results support individualized treatment approaches and highlight the need for larger, prospective validation studies.