The clinicopathological characteristics of POLE-mutated/ultramutated endometrial carcinoma and prognostic value of POLE status: a meta-analysis based on 49 articles incorporating 12,120 patients

Abstract

Objective: This study was designed to investigate the frequency and clinicopathological characteristics of POLE-mutated/ultramutated (POLEmut) in endometrial carcinoma (EC) and assess the prognostic values of POLE status. Methods: Electronic databases were screened to identify relevant studies. Meta-analysis was used to yield the pooled frequency of POLEmut and prognostic parameters by 95% confidence interval (CI), odd ratio (OR), and hazard ratio (HR). Results: Totally, 12,120 EC patients from 49 studies were included. The pooled frequency of POLEmut was 7.95% (95% CI: 6.52–9.51%) in EC, 7.95% (95% CI: 6.55–9.46%) in endometrioid endometrial carcinoma, and 4.45% (95% CI: 2.63–6.61%) in nonendometrioid endometrial carcinoma. A higher expression occurred in grade 3 (OR = 0.51, 95% CI: 0.36–0.73, P = 0.0002), FIGO stage I-II (OR = 1.91, 95% CI: 1.29–2.83, P = 0.0013), and myometrial invasion< 50% (OR = 0.66, 95% CI: 0.50–0.86, P = 0.0025). Survival analyses revealed favorable OS (HR = 0.68, 95% CI: 0.55–0.85, P = 0.0008), PFS (HR = 0.74, 95% CI: 0.59–0.93, P = 0.0085), DSS (HR = 0.61, 95% CI: 0.44–0.83, P = 0.0016), and RFS (HR = 0.47, 95% CI: 0.35–0.61, P < 0.0001) for POLEmut ECs. Additionally, the clinical outcomes of POLEmut group were the best, but those of p53-abnormal/mutated (p53abn) group were the worst, while those of microsatellite-instable (MSI)/hypermutated group and p53-wild-type (p53wt) group were medium. Conclusions: The POLEmut emergered higher expression in ECs with grade 3, FIGO stage I-II, and myometrial invasion< 50%; it might serve as a highly favorable prognostic marker in EC; the clinical outcomes of POLEmut group were the best one among the four molecular subtypes.