Clinical features of ProMisE groups identify different phenotypes of patients with endometrial cancer

Abstract

Background The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) groups has identified four molecular prognostic groups of endometrial cancer (EC): POLE-mutated (POLE-mt), mismatch repair-deficient (MMR-d), p53-abnormal (p53-abn), p53-wild-type (p53-wt). These groups might have different pathogenesis and risk factors, and might occur in different phenotypes of patients. However, these data are still lacking. Objective To provide a clinical characterization of the ProMisE groups of EC. Methods A systematic review and meta-analysis was performed by searching seven electronic databases from their inception to December 2020, for all studies reporting clinical characteristics of EC patients in each ProMisE group. Pooled means of age and BMI and pooled prevalence of FIGO stage I and adjuvant treatment in each ProMisE group were calculated. Results Six studies with 1, 879 women were included in the systematic review. Pooled means (with standard error) and prevalence values were: in the MMR-d group, age = 66.5 ± 0.6; BMI = 30.6 ± 1.2; stage I = 72.6%; adjuvant treatment = 47.3%; in the POLE-mt group, age = 58.6 ± 2.7; BMI = 27.2 ± 0.9; stage I = 93.7%; adjuvant treatment = 53.6%; in the p53-wt group, age = 64.2 ± 1.9; BMI = 32.3 ± 1.4; stage I = 80.5%; adjuvant treatment = 45.3%; in the p53-abn group, age = 71.1 ± 0.5; BMI = 29.1 ± 0.5; stage I = 50.8%; adjuvant treatment = 64.4%. Conclusion The ProMisE groups identify different phenotypes of patients. The POLE-mt group included the youngest women, with the lower BMI and the highest prevalence of stage I. The p53-wt group included patients with the highest BMI. The p53-abn group included the oldest women, with the highest prevalence of adjuvant treatment and the lowest prevalence of stage I. The MMR-d group showed intermediate values among the ProMisE groups for all clinical features.

Identification of Distinct Molecular Subtypes of Endometrioid Adenocarcinoma

“…For example, subtype I cases identified in our study had a high percentage of stage I and grade I–II, and less tumor invasion with favorite prognosis. These characteristics were similar to these EC cases in p53wt group identified in ProMisE, which also had the high prevalence of stage I and low-grade and low prevalence of lymphovascular space invasion with the good to moderate prognosis ( Raffone et al, 2020 , 2021a ). While the subtype II cases in our study had an analogous molecular features with the group5 EC cases named “TP53 mutated/Non-homologous End-Joining positive” group defined in Trans PORTEC ( Auguste et al, 2018 ), as both of them had high expression of DNA damage and PARP-1 expression with the worst prognosis.…”

“…ProMisE group contained the different molecular signatures compared to other methods, and could improve the ability to discern outcomes when it combined with the addition of select parameters. Moreover, a series of studies were conducted to analysis the clinical and histopathological characterization of ProMisE molecular groups, and revealed that ProMisE groups could identify different phenotypes of patients, and a great percentage of patients are currently under-or over treated (Raffone et al, 2020(Raffone et al, , 2021a. They also found that tumorinfiltrating lymphocytes might be considered in an integrate algorithm to identify POLE-mutated ECs when sequencing is unavailable (Raffone et al, 2021b).…”

New Pathological and Clinical Insights in Endometrial Cancer in View of the Updated ESGO/ESTRO/ESP Guidelines

“…The emphasis linked to the TCGA molecular groups has led to the hypothesis that molecular data might completely replace the traditional histopathological assessment [ 79 ]. However, the four TCGA groups may vary with regard to clinical and pathological features [ 22 , 80 ]; these factors may have a different prognostic impact across the several groups. For instance, the POLEmut group might be the least affected by other clinicopathological features.…”

Molecular Classification to Prognosticate Response in Medically Managed Endometrial Cancers and Endometrial Intraepithelial Neoplasia

“…Other studies have also reported that copy number-high/p53abn endometrioid tumors demonstrate increased biologic aggressiveness [31][32][33][34][35]. Cosgrove et al molecularly classified 982 endometrioid adenocarcinomas from NRG/GOG210 after completion of definitive surgery and adjuvant therapy [32].…”