Researchers at the Instituto Nacional de Câncer evaluated the status of the p53 tumor suppressor protein in 59 patients diagnosed with high-grade endometrial cancer without myometrial invasion, finding that all documented disease recurrences clustered exclusively within patients exhibiting abnormal p53 expression. The retrospective analysis, covering cases treated at the Brazilian institution between 2010 and 2025, utilized immunohistochemistry to investigate how p53 mutations influence patient relapse and survival trajectories in early-stage aggressive uterine tumors.
Patient Cohort and Histological Breakdown
The study cohort comprised 59 patients diagnosed with high-grade endometrial tumors who lacked invasion into the myometrium. The analyzed pathology encompassed several aggressive histological subtypes, including grade 3 endometrioid carcinoma, serous carcinoma, clear cell carcinoma, carcinosarcoma, and mixed or undifferentiated tumors. Within this group, 46 patients displayed abnormal p53 expression, while 13 patients demonstrated wild-type expression patterns. The vast majority of the cohort—specifically 94.9%—presented with Stage I disease, although three patients already exhibited disease dissemination outside the uterus at the time of evaluation.
Recurrence Patterns and Stage IC Concentration
Every single recurrence observed during the study period occurred within the abnormal p53 patient subset, whereas no patients with wild-type p53 experienced disease progression. Among 56 patients classified specifically under FIGO Stage IC, nine patients (equivalent to 16.1%) experienced a recurrence. The five-year recurrence estimate reached 23.2% for the abnormal p53 group compared to 0% for the wild-type group. Despite these clear distributional differences, variations in recurrence-free survival and overall survival curves did not reach statistical significance, a limitation researchers attributed to the small sample size.
Extrapelvic Relapse Locations and Mortality
Of the nine recurrences recorded in Stage IC patients, the physical distribution extended well beyond the pelvic cavity. Four recurrences remained pelvic, while three manifested in the abdomen and two presented as distant metastases. Consequently, five of the nine relapses occurred outside the pelvis, demonstrating that disease recurrence was not anatomically restricted to the pelvic region in this subset. By the final follow-up evaluation, seven patients in the Stage IC category had died. Six of those deaths occurred in the abnormal p53 group, and one death was recorded in the wild-type group.
Methodological Limitations and Future Validation Needs
Study authors emphasize that while p53 status holds clear potential for refining risk stratification in high-grade endometrial cancer without myometrial invasion, the current findings possess distinct methodological constraints. The retrospective design, small sample cohort, heterogeneity in surgical staging, and non-standardized administration of adjuvant therapy all limit immediate clinical application. The absence of uniform molecular testing beyond p53 also restricted a more comprehensive genomic classification. The research team stresses that these results require validation through larger prospective studies before they can alter definitive treatment guidelines.