TCGA molecular groups of endometrial cancer: Pooled data about prognosis

Antonio Raffone; Antonio Travaglino; Massimo Mascolo; Luigi Carbone; Maurizio Guida; Luigi Insabato; Fulvio Zullo

doi:10.1016/j.ygyno.2019.08.019

TCGA molecular groups of endometrial cancer: Pooled data about prognosis

Gynecol Oncol. 2019 Nov;155(2):374-383. doi: 10.1016/j.ygyno.2019.08.019. Epub 2019 Aug 29.

Authors

Antonio Raffone¹, Antonio Travaglino², Massimo Mascolo³, Luigi Carbone¹, Maurizio Guida¹, Luigi Insabato³, Fulvio Zullo¹

Affiliations

¹ Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples Federico II, Naples, Italy.
² Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy. Electronic address: antonio.travaglino@unina.it.
³ Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy.

PMID: 31472940
DOI: 10.1016/j.ygyno.2019.08.019

Abstract

Background: After The Cancer Genome Atlas (TCGA) findings, four novel prognostic groups may direct the management of endometrial cancer (EC): POLE-mutated/ultramutated (POLEmt), microsatellite-instable/hypermutated (MSI), copy-number-low/p53-wild-type (p53wt), and copy-number-high/p53-mutated (p53mt). However, data about prognosis in each group are different across the studies, and definitive pooled estimates are lacking after validation series. Such data may be crucial in directing clinical study design and establishing the optimal tailored management of patients.

Aim: To provide pooled estimates of hazard ratio (HR) for overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS) in each prognostic group.

Materials and methods: A systematic review and meta-analysis was performed by searching 7 electronic databases, from their inception to April 2019, for studies assessing prognosis in each TCGA EC group. Both univariable and multivariable HR analysis was performed for OS, DSS and PFS in each group, using p53wt as reference group.

Results: Six studies with 2818 patients were included. Regarding OS, pooled HRs were 3.179 and 1.986 for p53mt group, 1.522 and 1.192 for MSI group, and 0.589 and 0.795 for POLEmt group at univariable and multivariable analyses, respectively. Regarding DSS, pooled HR were 5.052 and 2.133 for p53mt group, 1.965 and 1.068 for MSI group, and 0.552 and 0.325 for POLEmt group at univariable and multivariable analyses, respectively. Regarding PFS, pooled HR were 3.512 and 1.833 for p53mt group, 1.354 and 0.817 for MSI group, and 0.287 and 0.217 for POLEmt group at univariable and multivariable analyses, respectively.

Conclusions: Prognosis of p53mt group is consistently the worst one and is further worsened by unfavorable clinicopathological factors. Prognosis of MSI group overlaps with p53wt group but is worsened by unfavorable clinicopathological factors. Prognosis of POLEmt group is the best one and does not seem to be significantly affected by clinicopathological factors.

Keywords: Endometrium; PROMISE; Prognosis; Risk assessment; Treatment.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Adult
Aged
Aged, 80 and over
Endometrial Neoplasms / genetics
Endometrial Neoplasms / mortality*
Epidemiologic Methods
Female
Genome, Human
Humans
Microsatellite Instability
Middle Aged
Mutation / genetics
Prognosis
Tumor Suppressor Protein p53 / metabolism

Substances

TP53 protein, human
Tumor Suppressor Protein p53