Impact of TP53 somatic mutations on prognosis in endometrial cancer: a systematic review and meta-analysis

Endometrial cancer (EC) is the sixth most common female cancer and may rank fourth in cancer mortality by 2040. TP53 mutations and aberrant p53 expression are associated to aggressive tumor subtypes and poor prognosis, reducing overall survival (OS), disease-free survival, recurrence rates (RcR) and Mortality Risk (MR). The prognostic impact of TP53 mutations in EC remains unclear.

A systematic search was conducted in PubMed, Embase, and the Cochrane Library. Hazard ratios (HR) and Risk Ratios (RR) with 95% confidence intervals (CI) were combined using random-effects models. Analyses were conducted in RStudio (v4.4.1), and heterogeneity was evaluated using the I² statistic, with p < 0.05 considered significant.

Twenty-four studies comprising 5462 EC patients were included. TP53 mutations and aberrant p53 expression were associated with poorer outcomes. For OS, TP53 mutations had an HR of 2.27 (95% CI 1.47-3.49) and aberrant p53 had an HR of 5.01 (95% CI 2.44-10.30). For DFS, TP53 mutations had an HR of 4.20 (95% CI 1.79-9.86), while aberrant p53 had an HR of 2.17 (95% CI 1.27-3.72). TP53 mutations also increased RcR (RR: 2.88; 95% CI 2.18-3.80) and MR (RR: 2.33; 95% CI 1.11-4.88). Aberrant p53 showed a non-significant trend for recurrence (RR: 3.54; 95% CI 0.95-13.10).

TP53 mutations and abnormal p53 expression in EC patients predict a poorer prognosis, characterized by increased RcR and MR, as well as lower DFS and OS.