The prognostic value of p53 abnormal expression in non-myoinvasive endometrial cancer: a retrospective comparative study according to p53 status and myometrial invasion.

OBJECTIVE

This study aimed to assess oncologic outcomes associated with p53 abnormal expression in non-myoinvasive endometrial cancer and contextualize these outcomes by comparison with tumors showing limited (< 50%) myometrial invasion and/or p53 wild-type expression.

METHODS

We retrospectively evaluated patients with uterine-confined endometrial cancer and < 50% myometrial invasion, no cervical invasion, and known p53 status, who underwent complete surgical staging at Mayo Clinic Rochester (1999-2022). All histologic sub-types were included; molecular characterization beyond p53 (including mismatch repair and POLE status) was not systematically available. Adjuvant treatment was administered according to clinicopathological characteristics and institutional practice. Patients' tumors were classified into 4 groups according to p53 status and the presence of myoinvasion: p53 abnormal (p53abn) tumors non-myoinvasive, p53abn tumors with < 50% myoinvasion, p53 wild-type (p53wt) tumors non-myoinvasive, and p53wt with < 50% myoinvasion. Kaplan-Meier curves and log-rank tests were reported for 5-year recurrence-free and overall survival. Univariate and multi-variable Cox proportional hazards models were fitted to identify factors associated with death and recurrence in the overall population.

RESULTS

Of the 473 patients, the focus is on 81 patients with p53abn non-myoinvasive endometrial cancer. This group showed an 88.1% (95% confidence interval [CI] 80.5 to 96.3) 5-year recurrence-free survival, with most recurrences being distant (75%). Among patients with p53abn tumors, overall survival did not differ between those with and without myometrial invasion (p53abn non-myoinvasive and p53abn with < 50% myoinvasion pairwise log-rank p =.63), although recurrence-free survival was significantly worse in the p53abn with < 50% myoinvasion group (p53abn non-myoinvasive and p53abn with < 50% myoinvasion pairwise log-rank p =.02). When p53abn non-myoinvasive tumors were compared with p53wt tumors, no differences in overall or recurrence-free survival were observed in pairwise analyses; however, overall survival was significantly shorter for p53abn non-myoinvasive tumors when all p53wt cases were combined (log-rank p =.04), whereas recurrence-free survival remained similar (log-rank p =.59). Abnormal p53 expression was associated with recurrence (hazard ratio [HR] 1.93, 95% CI 1.12 to 3.32) and shorter survival (HR 1.80, 95% CI 1.004 to 3.24), whereas the presence of myometrial invasion was not predictive of either overall or recurrence-free survival.

CONCLUSION

This retrospective study confirms the aggressive nature of p53abn tumors, even in the absence of myometrial invasion, underscoring the importance of molecular assessment in endometrium-confined tumors. These results warrant validation in larger, prospective cohorts.