Search Results (483)

Endometrial cancer (EC) is the most common gynecological cancer in developed countries, with approximately 417,000 new cases reported worldwide in 2020. Its incidence has been rising for the past 30 years, primarily due to population aging, obesity, and type 2 diabetes; obesity accounts for almost half of cases due to excessive estrogen production. The classic division into types I and II was replaced in 2013 by the molecular TCGA classification, which distinguishes four subtypes: POLE-ultramutated (best prognosis), MSI-hypermutated, copy-number low, and copy-number high (worst prognosis). This classification (refined in ProMisE and TransPORTEC) enables precise treatment: immunotherapy (pembrolizumab, dostarlimab) works excellently in dMMR/MSI-H tumors, PI3K/AKT/mTOR inhibitors and trastuzumab deruxtecan in selected molecular subtypes, and hormone therapy in ER-positive tumors. ctDNA monitoring supports therapeutic decisions. Integrating the molecular profile with FIGO allows for truly personalized treatment, although MMRp/MSS tumors remain a challenge. The future lies in multi-omics, new biomarkers, and combination therapies. Full article

Recurrent endometrial cancer (EC) has limited therapeutic options beyond platinum-based chemotherapy, highlighting the need to identify exploitable molecular vulnerabilities. Tumors with high genomic instability, including microsatellite instability-high (MSI-h) or copy-number-high (CNH) ECs, rely on the ATR-CHK1 signaling pathway to tolerate replication stress and maintain genome integrity, making this pathway an attractive therapeutic target. However, acquired resistance to ATR and CHK1 inhibitors (ATRi/CHK1i) often develops, and the transcriptomic basis of this resistance in EC remains unknown. Here, we established isogenic ATRi- and CHK1i-resistant cell line models from MSI-h (HEC1A) and CNH (ARK2) EC lineages and performed baseline transcriptomic profiling to characterize stable resistance-associated states. MSI-h-derived resistant clones adopted a unified transcriptional state enriched for epithelial-mesenchymal transition, cytokine signaling, and interferon responses, while ATRi-resistant models showing additional enrichment of developmental and KRAS/Notch-associated pathways. In contrast, CNH-derived resistant clones diverged by inhibitor class, with ATRi resistance preferentially enriching proliferation-associated pathways and CHK1i resistance inducing interferon signaling. Notably, THBS1, EDN1, and TENM2 were consistently upregulated across all resistant models relative to parental lines. Together, these findings demonstrate that acquired resistance to ATRi and CHK1i in EC is shaped by both lineage and inhibitor class and provide a transcriptomic framework that may inform future biomarker development and therapeutic strategies. Full article

Background: Precursor endometrial lesions and endometrial cancer are strongly influenced by lifestyle-related risk factors, including obesity, low physical activity, and unfavorable dietary patterns. Identifying these factors is essential for early prevention and for improving health literacy among women. Objective: The objective of this study was to evaluate the influence of modifiable lifestyle factors on the likelihood of developing EIN and endometrial cancer in comparison with leiomyoma. Materials and Methods: A cross-sectional analytical study was conducted among 50 women, divided into three groups: leiomyoma (n = 20), EIN (n = 15), and endometrial cancer (n = 15). BMI, physical activity, dietary habits, sleep duration, stress levels, and smoking status were assessed. Statistical analysis included the Kruskal–Wallis test, correlation analysis, and logistic regression. Results: BMI was identified as an independent predictor of EIN/EC (OR = 1.29; p = 0.015). Women with EIN/EC demonstrated significantly lower levels of physical activity (p = 0.018). A clustering of behavioral risks was observed: higher BMI was associated with higher stress and shorter sleep duration. Conclusions: Modifiable lifestyle factors play a key role in the development of precursor and malignant endometrial conditions. Targeted interventions focusing on weight management, increased physical activity, and improved health literacy may reduce risk and improve quality of life among peri- and postmenopausal women. Full article

Background/Objectives: Early and accurate characterization of endometrial cancer (EC) is crucial for patient management, but current imaging modalities lack in diagnostic accuracy and ability to assess molecular profiles. The aim of this study is to evaluate hybrid [¹⁸F]FDG PET/MRI’s diagnostic accuracy in EC staging and role in predicting tumor aggressiveness, molecular characterization, and recurrence. Methods: A prospective study (ClinicalTrials.gov, ID:NCT04212910) evaluating EC patients undergoing [¹⁸F]FDG PET/MRI before surgery (2018–2024). Histology, immunohistochemistry, and patients’ follow-up (mean FU time: 3.13y) were used as the reference standard. [¹⁸F]FDG PET/MRI, PET only, and MRI only were independently reviewed to assess the diagnostic accuracy (ACC), sensitivity (SN), specificity (SP), and positive/negative predictive value (PPV, NPV). Imaging parameters were extracted from [¹⁸F]FDG PET and pcT1w, T2w, DWI, and DCE MRI. Spearman’s correlations, Fisher’s exact test, ROC-AUC analysis, Kaplan–Meier survival curves, log-rank tests and Cox proportional hazards models were applied. Results: Eighty participants with primary EC (median age 63 ± 12 years) were enrolled, with 17% showing LN involvement. [¹⁸F]FDG PET/MRI provided ACC = 98.75%, SN = 98.75%, and PPV = 100% for primary tumor detection, and ACC = 92.41%, SN = 84.62%, SP = 93.94%, PPV = 73.33%, and NPV = 96.88% for LN detection. PET/MRI parameters predicted LN involvement (AUC = 79.49%), deep myometrial invasion (79.78%), lymphovascular space invasion (82.00%), p53abn (71.47%), MMRd (74.51%), relapse (82.00%), and postoperative administration of adjuvant therapy (79.64%). Patients with a tumor cranio-caudal diameter ≥ 43 mm and MTV ≥ 13.5 cm³ showed increased probabilities of recurrence (p < 0.001). Conclusions: [¹⁸F]FDG PET/MR showed exceptional accuracy in EC primary tumor and LN detection. Derived parameters demonstrated potential ability in defining features of aggressiveness, molecular alterations, and tumor recurrence. Full article

Introduction: Endometrial carcinoma (EC) is the most prevalent gynecological cancer. It is characterized by a clinical, pathological, and prognostic trajectory that has become inextricably linked to the disease’s molecular profile. Therefore, it is imperative to examine its relevance across all facets associated with the disease. Methods: This is a single-center retrospective study to assess tumor molecular profile concordance between EC diagnosis and recurrence. All patients who underwent hysterectomy for EC between 2016 and 2020 were included. Results: In total, 221 cases of EC were collected. In total, 18 recurrences were found. In two cases, there was a molecular classification (MC) change: an MMR-deficient endometrioid EC shifted to a “multiple classifier” subtype. The second, an NSMP subtype, at second recurrence revealed a switched MC to an aberrant mutated p53 profile. This discordance rate was non-significant in our cohort. However, considering the lack of evidence, it opens new insights to be revealed. Conclusions: This is the first study focusing on the discordance rate of MCs in EC relapses compared to the initial diagnosis. Future large-scale retrospective and prospective multicenter studies are essential for exploring this aspect. Full article

Background: As a newly recognized type of cell death implicated in cancer, ferroptosis plays multiple roles in tumor biology. Here, we sought to construct a prognostic framework for EC on the basis of ferroptosis-related long non-coding RNAs (FerlncRNAs), microRNAs (FermiRNAs), and mRNAs (FRGs) for endometrial cancer (EC). Methods: Transcriptomic profiles of tumors and matched clinical data for 544 EC patients were retrieved from TCGA-UCEC. A prognostic framework was generated through Cox regression, integrating ferroptosis-linked lncRNAs, miRNAs, and mRNAs. EC cases were stratified into groups with high or low predicted risk based on ferroptosis-related gene expression. The model’s prognostic utility was examined through Kaplan–Meier (K–M) analysis and receiver operating characteristic curves. Results: A prognostic model based on 16 RNAs, including 10 FerlncRNAs, 2 FermiRNAs, and 4 FRGs, was developed. Analysis using K–M plots showed that high-risk patients experienced shorter overall survival than their low-risk counterparts (p < 0.001). The model’s area under curve (AUC) values were 0.731, 0.749, and 0.768 at 1-, 3-, and 5-year time points, surpassing those of standard clinical parameters. Furthermore, in an external validation cohort, these signature RNAs were associated with EC prognosis. Conclusions: The novel ferroptosis-related lncRNA–miRNA–mRNA prognostic model provides a basis to assess clinical prognosis in EC patients. Full article

Background/Objectives: Currently, no non-invasive detection method for endometrial cancer (EC) is recommended in clinical practice worldwide. This study aimed to evaluate the clinical value of detecting DNA methylation of CDO1 and CELF4 (CDO1m/CELF4m) in exfoliated cervical cells for the detection of EC in women with suspected endometrial lesions. Methods: A total of 2164 patients scheduled for hysteroscopic surgery due to suspected endometrial lesions at the Obstetrics and Gynecology Hospital of Fudan University between July 2023 and May 2024 were prospectively enrolled. Preoperative exfoliated cervical cells were collected for dual-gene methylation testing. Clinical data and endometrial thickness measured by transvaginal sonography (TVS) were recorded. Hysteroscopic histopathological diagnosis served as the gold standard to evaluate the performance of methylation testing alone and in combination with TVS. Results: This study included 2164 patients, comprising 33 EC cases, 31 cases of endometrial intraepithelial neoplasia (EIN), and 2100 cases of non-endometrial lesions, with mean ages of 51.7 ± 6.4, 49.5 ± 8.9, and 44.7 ± 9.8 years, respectively (p < 0.001). For EC detection, CDO1m/CELF4m positivity showed a sensitivity of 93.94% (95% CI: 79.77–99.26%), specificity of 96.7% (95% CI: 95.92–97.47%), positive predictive value (PPV) of 31.0% (95% CI: 25.96–36.53%), and negative predictive value (NPV) of 99.90% (95% CI: 99.63–99.98%). For EIN detection, the sensitivity was 83.87%, specificity 97.95%, PPV 37.68%, and NPV 99.76%. Combining TVS with DNA methylation detection further improved the sensitivity and NPV for both EC and EIN detection. Conclusions: DNA methylation detection in exfoliated cervical cells demonstrates high sensitivity and specificity for EC detection. The combination with TVS further enhances sensitivity and NPV, offering a simple and non-invasive triage strategy for patients with suspected endometrial lesions. This study was registered in China Clinical Trial Registry (ChiCTR2200055991) on 30 January 2023. Full article

Background: Mismatch repair (MMR) and microsatellite instability (MSI) testing have become essential biomarkers in the molecular classification of endometrial cancer (EC), guiding adjuvant treatment decisions and eligibility for immune checkpoint inhibition. Although international guidelines recommend universal testing, real-world implementation remains heterogeneous. This study aimed to evaluate trends in MMR and MSI testing and associated molecular diagnostics in Germany between 2018 and 2022. Methods: A retrospective multicenter analysis was conducted across German tertiary care centers. Data from patients with histologically confirmed EC between 2018 and 2022 were extracted from standardized electronic pathology records. Annual testing rates for MSI, MMR, POLE, TP53, and L1CAM were analyzed using descriptive statistics and trend analysis (Chi-square test for trend, p < 0.05). Therapeutic data were collected to assess the use of immune checkpoint inhibitors. Results: There was a significant increase in the annual rates of molecular testing for MSI, POLE, TP53, and L1CAM over the five-year observation period (all p < 0.05). TP53 testing showed the highest increase (13.1% → 78.6%), while MSI testing rose from 82.9% to 97.4%. Both POLE and L1CAM testing were virtually absent in 2018 (0% and 1.6%) but reached 15.7% by 2022. Conclusions: This study demonstrates a rapid and substantial implementation of MMR and MSI testing in German clinical practice, reflecting successful translation of trial results into routine care. However, implementation of testing in guidelines appeared time-shifted. For bridging this gap, annual guideline updates seem to be necessary. Full article

Background and Objectives: Sentinel lymph node (SLN) mapping is an established alternative to systematic lymphadenectomy for early-stage endometrial cancer (EC). While retroperitoneal vNOTES affords direct access to pelvic nodes without abdominal incisions, data regarding its oncologic validity remain sparse. This study evaluates the SLN detection rates, perioperative outcomes, and 12-month oncologic outcomes oncologic results of retroperitoneal vNOTES mapping in presumed early-stage EC. Materials and Methods: This single-center retrospective cohort study analyzed consecutive patients undergoing retroperitoneal vNOTES staging (hysterectomy, BSO, and SLN mapping) for presumed EC between February 2023 and January 2024. Eligible patients had radiologically uterine-confined disease and were candidates for transvaginal surgery. Following cervical methylene blue injection, SLN mapping was executed via the retroperitoneal vNOTES route. Mapped and suspicious nodes were excised, with side-specific lymphadenectomy performed for failed mapping per algorithm. While perioperative outcomes were assessed for the full cohort, oncologic analyses (FIGO 2023 staging, nodal metastasis) were restricted to patients with confirmed carcinoma. Results: Of 98 patients (median age 54; BMI 31 kg/m²), final pathology confirmed carcinoma in 78 (73 endometrioid, 5 serous) and EIN in 20. Bilateral SLN mapping succeeded in 87.8% (86/98), necessitating side-specific lymphadenectomy in the remaining 12.2%. The obturator fossa was the predominant nodal basin (43.9%). Within the carcinoma cohort (n = 78), 57.7% were Grade 1 and 74.4% FIGO Stage I. Nodal metastases (FIGO IIIC1) were identified in 12.8% (10/78), all prompting adjuvant therapy. At a median follow-up of 12 months, no disease recurrences were observed. The complication rate was 6.1% (5.1% Clavien–Dindo ≥ III), with no conversions required. At 12-month follow-up, no recurrences were detected, though the absence of systematic lymphadenectomy precluded formal sensitivity analysis. Conclusions: Retroperitoneal vNOTES represents a feasible and safe strategy for SLN mapping in early-stage EC, demonstrating high bilateral detection with minimal morbidity. However, reliance on methylene blue and limited follow-up necessitate caution. Broader implementation requires validation through prospective, comparative trials utilizing indocyanine green and long-term oncologic surveillance. Full article

Endometrial carcinoma (EC) continues to represent a major cause of gynecologic cancer–related mortality among women worldwide. Its multifactorial etiopathogenesis and underlying molecular heterogeneity have been the focus of extensive investigation. While traditional histological classification provides essential diagnostic insight, it is limited in predicting prognosis and therapeutic response due to significant interobserver variability. Recent advances in molecular biology and cancer genomics have profoundly enhanced understanding of EC pathogenesis. The Cancer Genome Atlas (TCGA) project delineated four distinct molecular subtypes of EC, POLE ultra-mutated, microsatellite instability hypermutated (MSI-H), copy number low (CNL) and copy number high (CNH), each defined by unique genomic alterations, histopathologic features, and clinical behaviors. These molecular groups demonstrate significant prognostic and therapeutic implications, correlating with differential outcomes and treatment responses. This review summarizes current evidence on the genomic landscape of endometrial carcinoma and underscores the pivotal role of molecular classification in improving diagnostic accuracy, prognostic stratification, and personalized therapy. Ongoing research into molecular biomarkers holds promise for refining patient management and optimizing clinical outcomes. Full article

Background/Objectives: Endometrial hyperplasia (EH) is a pathology of the uterus, which is a pathological overgrowth of the endometrial glands associated with the risk of progression to endometrial cancer (EC). The purpose of this study was to conduct a retrospective comparative analysis of the medical and social characteristics of women with endometrial hyperplasia (EH) across two time periods (2016–2017 and 2023–2024) in Almaty, the largest city in Kazakhstan. Methods: A retrospective comparative analysis included 376 women (188 per period) with histologically confirmed EH treated in public and private healthcare facilities. Data were extracted from electronic medical systems (Damumed, Avicenna). Group differences were evaluated using the χ² test, Fisher’s exact test, and Mann–Whitney U test. Odds ratios (OR) with 95% confidence intervals (CI) were calculated; significance was set at p < 0.05. Results: The proportion of postmenopausal women increased from 22.3% to 37.8% (OR: 2.11, 95% CI: 1.34–3.32, p < 0.001), and self-referrals to private clinics rose from 17.6% to 37.2% (OR: 2.79, 95% CI 1.73–4.49, p < 0.001). Women with higher education became more prevalent (from 26.1% to 43.6%, OR: 2.19, 95% CI: 1.42–3.39, p < 0.001), along with an increase in endocrine and metabolic disorders such as thyroid disease (from 4.8% to 12.2%, OR: 2.77, 95% CI: 1.25–6.16) and overweight status (from 51.6% to 65.4%, OR: 1.78, 95% CI: 1.17–2.69, p = 0.020). Asymptomatic cases were more frequently detected (from 18.6% to 28.2%, OR: 1.72, CI: 1.06–2.79, p = 0.028), and diagnostic approaches shifted from blind curettage (78.2% vs. 47.3%, OR: 0.25, CI: 0.16–0.39, p < 0.001) toward hysteroscopy with biopsy (from 21.3% to 53.7%, OR: 4.30, CI: 2.73–6.75, p < 0.001). Conclusions: Over seven years, the clinical and socio-demographic composition of women with EH in Almaty has changed toward older, more educated, and metabolically burdened populations, with broader access to minimally invasive diagnostic methods. The findings describe observable structural changes and risk group patterns, emphasizing the importance of prospective, registry-based, and molecularly oriented studies to refine clinical strategies for prevention and early detection. Full article

Endometrial cancer is the fourth most diagnosed cancer in U.S. women. Diabetes and obesity are established independent risk factors for EC, but their combined effect is less defined. This review investigates the literature on these comorbidities as risk factors and modifiers of EC. Multiple cohort and case–control investigations have shown an increased relative risk (RR) and odds ratio (OR) when diabetes and obesity coexist. In one prospective cohort, the RR of EC in diabetic women was 1.94 [95% CI, 1.23–3.08], but increased to 6.39 [95% CI, 3.28–12.06] with obesity; with low physical activity added, RR rose to 9.61 [95% CI, 4.66–19.83]. Case–control studies similarly show an OR of 1.4 [95% CI, 0.9–2.4] for diabetes alone, vs. 5.1 [95% CI, 3.0–8.7] with BMI > 30 and diabetes. Mechanistically, both conditions promote a pro-cancerous microenvironment through metabolic and inflammatory pathways. They also worsen treatment outcomes, with greater surgical complications, thromboembolic events (p < 0.01), prolonged hospitalizations 6.2 days versus 4.5 days (p < 0.03), and poorer survival with an elevated cancer-specific mortality (HR = 2.65, 95% CI 1.60–4.40). These findings underscore the urgent need for targeted interventions and translational research on how these comorbidities impact the pathophysiologic processes of EC. Full article

Objectives: This study aimed to evaluate the introduction of sentinel lymph node biopsy (SLNB) in early-stage endometrial cancer (EC), its learning curve, and factors influencing discrepancies between surgeons and pathologists. Methods: A single-centre retrospective observational study was conducted from June 2019 to December 2024 at the Department of Obstetrics and Gynecology, University Hospital Brno and Faculty of Medicine, Masaryk University. Patients with EC with complete preoperative staging and planned for extrafascial hysterectomy with bilateral salpingo-oophorectomy and SLNB were included. Bilateral detection rates were compared among two main surgeons—one senior fellow (A) and one junior fellow (B)—and other supervised fellows. Learning curves were assessed using detection rates and cumulative sum analysis. Risk factors for failed detection were analysed. Results: In 337 patients, overall bilateral detection rates ranged from 80–92%. Surgeon A achieved 80% success by the 30th procedure and 89% at the 74th. Surgeon B, trained under A’s supervision, reached 89% but later showed a decline after operating independently. The highest concordance with pathologists was noted for Surgeon A (94.6%), followed by B (92.2%) and others (84.9%). Discrepancies were mainly associated with the presence of fibroids (p = 0.005) and adenomyosis (p = 0.018). Conclusions: SNB in EC demonstrates an optimal learning curve that can be shortened through expert guidance. Extending supervised training to 30–35 procedures reduces post-independence decline and sustains high detection rates. Bilateral success, reflecting surgeon–pathologist concordance, is a strong indicator of the quality of a Gynecologic Oncology centre. Full article

Background: The incidence of endometrial cancer (EC) is rising globally across all age groups. Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion that may progress to EC if untreated. A clinical model is needed to efficiently identify women requiring prompt evaluation while avoiding unnecessary invasive procedures. Obesity is a major risk factor, but whether Asian women require a lower body mass index (BMI) cutoff than the World Health Organization (WHO) definition remains debated. This study aimed to develop a multivariable risk prediction model to guide biopsy decisions and determine an appropriate BMI cutoff for predicting EIN/EC risk among Asian women. Methods: This study retrospectively reviewed 1192 women aged ≥18 years who underwent hysteroscopy between 2010 and 2023 at a tertiary hospital. Candidate predictors included patient age, parity, BMI, postmenopausal status, symptom of abnormal uterine bleeding (AUB), diabetes mellitus, hypertension, polycystic ovary syndrome (PCOS), use of oral contraceptives, intrauterine devices, or menopausal hormone therapy, tamoxifen treatment, presence of multiple polyps, and endometrial thickness (EMT) measured by transvaginal ultrasonography. Multivariable logistic regression with stepwise selection identified independent predictors, and model stability and calibration were assessed using 1000 bootstrap resamples. Results: EIN/EC was diagnosed in 55 patients (4.6%). Six independent predictors were identified: postmenopausal status (adjusted odds ratio [aOR] 5.93, 95% CI 2.92–12.04), AUB (aOR 4.07, 1.51–10.97), multiple polyps (aOR 2.49, 1.33–4.66), PCOS (aOR 2.37, 1.08–5.22), BMI (aOR 1.13 per kg/m²; 1.84 per +5 kg/m²), and EMT (aOR 1.07 per mm, 1.02–1.11). When using categorical cutoffs, Obese II (BMI ≥ 30 kg/m²) and markedly increased EMT (≥20 mm) remained significant. Predicted probabilities ranged from 0.3% with no risk factors to 90.9% with all six risk factors present. The final model demonstrated good discrimination (AUC 0.79, 95% CI 0.73–0.86) and excellent calibration on bootstrap validation (mean absolute error 0.005). Conclusions: This six-factor clinical model stratifies individual EIN/EC risk using readily available variables and may guide timely, risk-based biopsy decisions by identifying high-risk patients while minimizing unnecessary procedures in low-risk cases. BMI ≥ 30 kg/m² (WHO obesity threshold) was confirmed as a meaningful cutoff, but external validation is warranted to confirm its generalizability and clinical applicability. Full article

Endometrial cancers (ECs) are mainly adenocarcinomas arising from the uterine endometrium. In this work, we employed data-independent acquisition (DIA) mass spectrometry (MS)-based label-free quantification (LFQ-MS) proteomics to analyze the proteome of tissue washings collected from 25 control (CTRL) subjects, 25 patients with low-grade type 1 endometrial cancer (EC), and 24 patients with high-grade type 1 EC. Following quantification and statistical analysis, we identified 42 proteins able to discriminate CTRL from EC patients, and 151 proteins differentiating high-grade EC cases from low-grade EC cases. Notably, PRRC2A and SYDE2 effectively distinguished both EC patients from controls and advanced EC cases from low-grade EC cases. Validation by Western blot analysis in an independent cohort comprising 19 CTRL patients, 19 patients with low-grade EC, and 19 patients with high-grade EC confirmed the upregulation of PRRC2A and SYDE2. These proteins are implicated in the translocation of SLC2A4, the regulation of MECP2, and extracellular matrix (ECM) proteoglycan pathways, all of which are associated with tumor growth. Our results demonstrate that DIA-based proteomic analysis of tissue washings enables the identification of potential biomarkers for endometrial cancer (EC). Moreover, this study highlights tissue washings as a promising biological fluid for biomarker discovery in EC. Full article