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); I² = 88%) and disease progression (HR, 1.63; 95% CI, 1.42–1.88; I² = 2%) compared with patients with wildtype p53 G3 endometrial cancer. The global pooled prevalence of abnormal p53 was 30% (95% CI, 25–34%; tau² = 0.02; I² = 74%), with the highest prevalence being found in studies conducted in Asia (95% CI, 27–41%; tau² = 0.01; I² = 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.

Endometrial cancer of no specific molecular profile (NSMP) represents the most prevalent molecular subtype of endometrial cancer, comprising over 50 % of all diagnoses. Although studies have explored the prevalence of the NSMP subtype, to our knowledge, no systematic review or meta-analysis has specifically targeted grade 3 (G3, high-grade) tumors. We aimed to determine the prevalence of G3 endometrioid endometrial cancer of NSMP and assess regional variations in this prevalence. We also sought to synthesize available data concerning oncologic outcomes, including overall survival, progression-free survival, and disease-specific survival. We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO No: CRD42024544247). We searched the electronic databases: PubMed/Medline, Scopus, Web of Science, Cochrane Library, and EMBASE. To estimate the overall prevalence of the NSMP subtype, we performed a meta-analysis using the proportions method with the Freeman-Tukey (arcsine) transformation. For estimating oncologic outcomes, we conducted a meta-analysis using hazard ratios (HRs) when available. In the absence of HRs, we utilized Kaplan-Meier curves. All pooled estimates and their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model with the inverse variance method and restricted maximum likelihood estimator. We analyzed 31 studies, encompassing 2,660 patients. The pooled prevalence of NSMP within G3 endometrioid endometrial cancer was 0.29 (95 %CI: 0.23-0.34, I² = 80.8 %). This prevalence was highest in North America (0.43, 95 %CI: 0.17-0.71) and lowest in Europe (0.23, 95 %CI: 0.19-0.28). The random-effects pooled estimate indicated that the NSMP subtype was associated with intermediate oncologic outcomes compared to other molecular subtypes. The pooled prevalence of G3 endometrioid endometrial cancer of NSMP is 29 %. The oncologic outcomes for this molecular subtype seem intermediate, though further refinement and research are needed for a more precise understanding.

The treatment of recurrent ovarian cancer has been based on systemic therapy. The role of secondary cytoreductive surgery has been addressed recently in several trials. Imaging plays a key role in helping the surgical team to decide which patients will have resectable disease and benefit from surgery. The role of staging laparoscopy and several imaging and clinical scores has been extensively debated in the field. In other surgical fields there have been reports of using 3D imaging software and 3D printed models to help surgeons better plan the surgical approach. To the best of our knowledge, we report the first case of a patient with recurrent ovarian cancer undergoing 3D modeling before secondary cytoreductive surgery. The 3D modeling was of most value to evaluate the extension of the disease in our patient who underwent a successful secondary cytoreductive surgery and is currently free of the disease.

Endometrial cancer incidence is markedly rising globally, posing an urgent need to elucidate the molecular mechanisms driving disease characterization and progression. Endometrial cancer evolution is driven by canonical Wnt and p53 pathway alterations, yet the mechanisms orchestrating the transition from localized proliferation to stromal invasion, the proliferation–invasion dichotomy, remain poorly understood. While long non-coding RNAs (lncRNAs) are emerging as critical correlates of divergent tumor phenotypes, their coordination with the broader ubiquitin–proteasome system (UPS), specifically E3 ligase and deubiquitinase (DUB) networks, during endometrial cancer progression is largely unexplored. Whole-transcriptome RNA sequencing was performed on formalin-fixed paraffin-embedded (FFPE) tissue from a clinical cohort of 38 patients, comprising 34 primary endometrial carcinomas across distinct molecular subtypes (MSI, POLE, p53abn, and NSMP) and four pre-cancerous endometrial intraepithelial neoplasia (EIN) lesions. To stringently control for baseline patient-specific confounding, differential gene expression and principal component analyses were executed using a strict, intra-patient, matched-pair design (Tumor vs. Adjacent Normal). A principal component analysis of the batch-corrected transcriptome revealed a profound divergence between tumor and paired adjacent normal phenotypes. This spatial divergence was heavily characterized by lncRNA signatures (including SOCS2-AS1) strongly associated with extracellular matrix (ECM) remodeling. Concurrently, we identified a critical, malignancy-specific transcriptomic dysregulation across the broader UPS network. Within this altered transcriptional landscape, the ubiquitin C-terminal hydrolase (UCHL) family emerged as a highly significant node. UCHL5 displayed robust, global upregulation across the pan-cancer cohort compared with matched controls (log₂FC = 0.83, padj < 0.001). Strikingly, UCHL3 exhibited global upregulation (log₂FC = 1.23, padj = 0.002) that was highly concentrated within the microsatellite instability (MSI) and polymerase epsilon (POLE) hypermutated subtypes, highlighting a potential compensatory transcriptomic response to the predicted cellular stress inherent to high mutational burdens. In an exploratory subset of pre-cancerous EIN lesions (n = 4), neither the invasive lncRNA networks nor profound UPS/UCHL dysregulation were observed, suggesting a preliminary trend that requires validation in larger precursor cohorts. Our paired transcriptomic mapping reveals that endometrial cancer progression is characterized by divergent transcriptomic programs: specific lncRNA networks are tightly coupled to the invasive remodeling of the ECM, while concurrent dysregulation of broad UPS networks reflects the altered proteostasis associated with this phenotypic shift. The pronounced upregulation of critical UPS nodes, such as UCHL3 in MSI/POLE tumors, highlights a landscape of novel, enzymatically targetable vulnerabilities in hypermutated endometrial cancers.