Impact of <i>TP53</i> somatic mutations on prognosis in endometrial cancer: A systematic review and meta-analysis.

Abstract

e17618 Background: Endometrial cancer (EC) is the sixth most common cancer affecting women globally and is projected to become the fourth leading cause of cancer-related mortality among women by 2040. Mutations in the TP53 gene and aberrant expression of the p53 protein are strongly associated with aggressive histological subtypes and poor prognosis. These molecular alterations are linked to reduced overall survival (OS), disease-free survival (DFS), and higher recurrence rates (RR). Despite advancements in targeted therapies, the prognostic implications of p53 mutations have not been thoroughly explored. In this study, we conducted a systematic review and meta-analysis to evaluate the impact of TP53 -mutation and aberrant-p53 on OS, DFS, and RR in patients with EC. Methods: A literature search was conducted using the Medline, Embase, and Cochrane Library databases to investigate studies evaluating the impact of somatic TP53 mutation or abnormal expression of the p53 protein on prognosis in patients with endometrial cancer. Hazard ratios (HR) and odds ratios (OR) with 95% confidence intervals (CI) were estimated using a random-effects model. The meta-analysis was performed using RStudio version 4.4.1, and heterogeneity was assessed using the I² statistic. Statistical significance was defined as p &lt; 0.05. Results: Our meta-analysis included 21 studies, comprising a total of 6030 patients. The analysis of OS demonstrated significantly worse survival in the TP53 -mutation group (HR 3.4812; 95% CI 1.6971–7.1406; P &lt; 0.001; I² = 92.9%) and the aberrant-p53 group (HR 6.2784; 95% CI 2.4972–15.7847; P &lt; 0.001; I² = 71.3%). For DFS, statistically significant differences were observed, favoring TP53 -normal over TP53 -mutation (HR 3.8205; 95% CI 1.6479–8.8572; P = 0.002; I² = 77.5%) and normal-p53 over aberrant-p53 (HR 2.1723; 95% CI 1.2680–3.7214; P = 0.005; I² = 0%). Additionally, RR was significantly higher in the TP53 -mutation group (OR 0.2520; 95% CI 0.1711–0.3712; P &lt; 0.0001; I² = 0%) and in the aberrant-p53 group (OR 0.1969; 95% CI 0.0469–0.8264; P = 0.026; I² = 51.5%). Conclusions: This meta-analysis indicates that patients with EC and TP53 -mutation or aberrant-p53 have a significantly worse prognosis, with increased mortality, lower DFS, and higher recurrence rates than EC and TP53 -normal or p53-normal.