Abnormal P53 High-Grade Endometrioid Endometrial Cancer: A Systematic Review and Meta-Analysis

Overview

Journal Cancers (Basel)

Publisher MDPI

Date 2025 Jan 11

PMID 39796669

Authors

Joao Casanova

Alexandru Babiciu

Goncalo S Duarte

Ana Gomes da Costa

Sofia Silverio Serra

Teresa Costa

Ana Catarino

Mario M Leitao Jr

Jorge Lima

Affiliations

Soon will be listed here.

Abstract

Objective: Our primary objective was to evaluate the oncologic outcomes of patients with abnormal p53 FIGO grade 3 (high-grade) endometrioid endometrial cancer. As secondary objectives, we determined the global prevalence of abnormal p53 in grade 3 endometrioid endometrial carcinomas and the geographical variations.

Methods: The following electronic databases were searched: PubMed/Medline, EMBASE, Cochrane Library, Scopus, and Web of Science. We followed the Meta-Analysis for Observational Studies in Epidemiology guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. This review was preregistered with PROSPERO (no: CRD42023495192). Bias was assessed using the Quality in Prognosis Studies tool. For time-to-event data, the effect of p53 status on grade 3 endometrial cancer was described using hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). Overall survival and progression-free survival were analyzed using one- and two-stage approaches, the Kaplan-Meier method, and Cox proportional hazards models.

Results: Fifty-seven studies with 2528 patients were included. Patients with abnormal p53 had an increased risk of death (HR, 1.29 (95% CI, 1.11-1.48); I = 88%) and disease progression (HR, 1.63; 95% CI, 1.42-1.88; I = 2%) compared with patients with wildtype p53 G3 endometrial cancer. The global pooled prevalence of abnormal p53 was 30% (95% CI, 25-34%; tau = 0.02; I = 74%), with the highest prevalence being found in studies conducted in Asia (95% CI, 27-41%; tau = 0.01; I = 52%).

Conclusions: Abnormal p53 grade 3 endometrioid endometrial cancer is more common in Asia, and it is associated with decreased overall survival and progression-free survival.

References

Inaba F, Kawamata H, Teramoto T, Fukasawa I, Inaba N, Fujimori T . PTEN and p53 abnormalities are indicative and predictive factors for endometrial carcinoma. Oncol Rep. 2004; 13(1):17-24. View

Nout R, Bosse T, Creutzberg C, Jurgenliemk-Schulz I, Jobsen J, Lutgens L . Improved risk assessment of endometrial cancer by combined analysis of MSI, PI3K-AKT, Wnt/β-catenin and P53 pathway activation. Gynecol Oncol. 2012; 126(3):466-73. DOI: 10.1016/j.ygyno.2012.05.012. View

Yamauchi N, Sakamoto A, Uozaki H, Iihara K, Machinami R . Immunohistochemical analysis of endometrial adenocarcinoma for bcl-2 and p53 in relation to expression of sex steroid receptor and proliferative activity. Int J Gynecol Pathol. 1996; 15(3):202-8. DOI: 10.1097/00004347-199607000-00003. View

Mazurek A, Kuc P, Mazurek-Wadolkowska E, Laudanski T . A role of thymidine phosphorylase and P53 tissue protein expression in biology of endometrial cancer. Neoplasma. 2008; 55(3):261-5. View

Rios-Doria E, Momeni-Boroujeni A, Friedman C, Selenica P, Zhou Q, Wu M . Integration of clinical sequencing and immunohistochemistry for the molecular classification of endometrial carcinoma. Gynecol Oncol. 2023; 174:262-272. PMC: 10402916. DOI: 10.1016/j.ygyno.2023.05.059. View

Tresa A, Sambasivan S, Rema P, Dinesh D, Sivaranjith J, Nair S . Clinical Profile and Survival Outcome of Endometrial Cancer with p53 Mutation. Indian J Surg Oncol. 2022; 13(3):580-586. PMC: 9515295. DOI: 10.1007/s13193-022-01523-9. View

Jones M, Kounelis S, Hsu C, Papadaki H, Bakker A, Swalsky P . Prognostic value of p53 and K-ras-2 topographic genotyping in endometrial carcinoma: a clinicopathologic and molecular comparison. Int J Gynecol Pathol. 1998; 16(4):354-60. DOI: 10.1097/00004347-199710000-00010. View

Daniilidou K, Frangou-Plemenou M, Grammatikakis J, Grigoriou O, Vitoratos N, Kondi-Pafiti A . Prognostic significance and diagnostic value of PTEN and p53 expression in endometrial carcinoma. A retrospective clinicopathological and immunohistochemical study. J BUON. 2013; 18(1):195-201. View

Da Cruz Paula A, DeLair D, Ferrando L, Fix D, Soslow R, Park K . Genetic and molecular subtype heterogeneity in newly diagnosed early- and advanced-stage endometrial cancer. Gynecol Oncol. 2021; 161(2):535-544. PMC: 8085053. DOI: 10.1016/j.ygyno.2021.02.015. View

10.

Schultheis A, Martelotto L, De Filippo M, Piscuglio S, Ng C, Hussein Y . TP53 Mutational Spectrum in Endometrioid and Serous Endometrial Cancers. Int J Gynecol Pathol. 2015; 35(4):289-300. PMC: 5087968. DOI: 10.1097/PGP.0000000000000243. View

11.

Kandoth C, Schultz N, Cherniack A, Akbani R, Liu Y, Shen H . Integrated genomic characterization of endometrial carcinoma. Nature. 2013; 497(7447):67-73. PMC: 3704730. DOI: 10.1038/nature12113. View

12.

Matsumoto N, Manrai P, Rottmann D, Wu X, Assem H, Hui P . Correlative Assessment of p53 Immunostaining Patterns and TP53 Mutation Status by Next-Generation Sequencing in High-Grade Endometrial Carcinomas. Int J Gynecol Pathol. 2023; 42(6):567-575. DOI: 10.1097/PGP.0000000000000930. View

13.

Donehower L, Soussi T, Korkut A, Liu Y, Schultz A, Cardenas M . Integrated Analysis of TP53 Gene and Pathway Alterations in The Cancer Genome Atlas. Cell Rep. 2019; 28(5):1370-1384.e5. PMC: 7546539. DOI: 10.1016/j.celrep.2019.07.001. View

14.

Shiozawa T, Xin L, Nikaido T, Fujii S . Immunohistochemical detection of cyclin A with reference to p53 expression in endometrial endometrioid carcinomas. Int J Gynecol Pathol. 1998; 16(4):348-53. DOI: 10.1097/00004347-199710000-00009. View

15.

Bokhman J . Two pathogenetic types of endometrial carcinoma. Gynecol Oncol. 1983; 15(1):10-7. DOI: 10.1016/0090-8258(83)90111-7. View

16.

Cuevas D, Valls J, Gatius S, Roman-Canal B, Estaran E, Dorca E . Targeted sequencing with a customized panel to assess histological typing in endometrial carcinoma. Virchows Arch. 2019; 474(5):585-598. DOI: 10.1007/s00428-018-02516-2. View

17.

Oreskovic S, Babic D, Kalafatic D, Barisic D, Beketic-Oreskovic L . A significance of immunohistochemical determination of steroid receptors, cell proliferation factor Ki-67 and protein p53 in endometrial carcinoma. Gynecol Oncol. 2004; 93(1):34-40. DOI: 10.1016/j.ygyno.2003.12.038. View

18.

Van den Heerik A, Horeweg N, Nout R, Lutgens L, van der Steen-Banasik E, Westerveld G . PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer. Int J Gynecol Cancer. 2020; 30(12):2002-2007. PMC: 7788476. DOI: 10.1136/ijgc-2020-001929. View

19.

Beinse G, Rance B, Just P, Izac B, Letourneur F, Saidu N . Identification of mutated group using a molecular and immunohistochemical classification of endometrial carcinoma to improve prognostic evaluation for adjuvant treatments. Int J Gynecol Cancer. 2020; 30(5):640-647. DOI: 10.1136/ijgc-2019-000871. View

20.

Casanova J, Duarte G, da Costa A, Catarino A, Nave M, Antunes T . Prognosis of polymerase epsilon (POLE) mutation in high-grade endometrioid endometrial cancer: Systematic review and meta-analysis. Gynecol Oncol. 2024; 182:99-107. PMC: 11290341. DOI: 10.1016/j.ygyno.2024.01.018. View