Search Results (1,787)

Endometrial carcinoma is a biologically and clinically heterogeneous neoplasm, for which molecular classification now plays a central role in determining prognosis and guiding treatment. The aim of this study was to develop and apply an in-house multi-gene NGS panel to expand the molecular characterization of endometrial tumors beyond the markers required for surrogate classification. Seventy primary endometrial carcinomas were selected and analyzed by immunohistochemistry for p53, mismatch repair proteins, ARID1A, and PTEN, and by NGS on DNA extracted from FFPE samples using a panel comprising 28 genes. Molecular classification was assigned according to the WHO algorithm into the subgroups POLE-mutated, MMR-deficient, p53-abnormal, and NSMP (No Specific Molecular Profile). Sixty-eight cases were evaluable by sequencing, and in 93% at least one pathogenic, likely pathogenic, or variant of uncertain significance was identified. The most frequent alterations involved PTEN, PIK3CA, ARID1A, and TP53. POLE-mutated tumors showed the highest mutational burden, while CTNNB1 alterations were predominantly associated with the NSMP subgroup. Overall, the proposed panel proved to be a useful tool for complementing conventional molecular classification and for highlighting additional genomic differences that may be biologically and clinically relevant. Full article

Cancer-associated thrombosis (CAT) is defined as venous or arterial thrombotic events occurring in patients with active malignancy or during anticancer treatment, most commonly presenting as venous thromboembolism and representing a leading cause of morbidity and mortality in oncology. Hormone-sensitive malignancies, including breast, ovarian, and endometrial cancers, are characterized by a complex interaction among tumor biology, endocrine signaling, inflammation, endothelial dysfunction, and coagulation activation. In these malignancies, venous thromboembolism (VTE) risk is influenced not only by intrinsic tumor-related mechanisms but also by patient-specific factors and anticancer therapies, particularly endocrine treatments, chemotherapy, targeted agents, and extensive surgical procedures. Breast cancer is generally associated with an intermediate thrombotic risk, although endocrine therapy—especially tamoxifen—significantly increases VTE incidence. Ovarian cancer represents one of the most thrombogenic solid tumors because of elevated tissue factor expression, inflammatory activation, advanced-stage presentation, and aggressive multimodal treatment strategies. Endometrial cancer exhibits a strong association with obesity, metabolic syndrome, prolonged estrogen exposure, and perioperative thrombotic complications. Emerging evidence highlights the role of immune-thrombosis, extracellular vesicles, inflammatory cytokines, and sex-specific coagulation pathways in cancer-associated hypercoagulability. Current guidelines increasingly support individualized thromboprophylaxis based on tumor biology, patient-specific risk factors, and bleeding risk assessment. This review summarizes the biological mechanisms linking hormones and thrombosis in breast and gynecologic cancers, discusses current evidence regarding VTE risk factors and treatment-related thrombotic complications, and explores modern approaches to biomarkers, risk stratification, and personalized thromboprophylaxis. Full article

Cancer remains one of the leading causes of global mortality, with its incidence continuing to rise due to population growth, aging, lifestyle factors, and environmental exposures. Despite significant advances in early diagnosis and therapeutic strategies, the clinical management of cancer is still hindered by drug resistance, limited selectivity, and treatment-related toxicity. Consequently, increasing attention has been directed toward natural products as sources of novel anticancer agents with improved efficacy and reduced adverse effects. Pogostemon cablin (patchouli), a medicinal plant widely used in traditional medicine, has emerged as a promising candidate owing to its diverse bioactive constituents and broad pharmacological properties. This review systematically summarizes and critically evaluates current evidence on the anticancer potential of patchouli leaves, with particular emphasis on molecular mechanisms and translational relevance. Based on available experimental and preclinical studies, patchouli and its major phytochemicals exhibit notable anticancer activity against a wide range of malignancies, including endometrial, ovarian, liver, skin, nasopharyngeal, prostate, hematological, colorectal, and lung cancers. Mechanistically, these effects are primarily associated with the modulation of apoptosis, cell cycle regulation, oxidative stress, and key oncogenic signaling pathways, as well as potential synergistic interactions with conventional chemotherapeutic agents. Overall, this review highlights the therapeutic promise of patchouli leaves as a source of anticancer agents, identifies current knowledge gaps, and outlines future research directions to facilitate their development and clinical translation. Full article

Background and Objectives: Endometriosis is associated with chronic inflammation, immune dysregulation, oestrogen-dependent growth, oxidative stress, altered steroid hormone metabolism, compromised epithelial barrier integrity, and the production of bioactive microbial metabolites. These interconnected alterations have been proposed to create, in principle, a permissive local microenvironment for malignant transformation. This narrative review examines whether endometriosis-associated dysregulation of the gut and reproductive tract microbiota may act as a hypothetical biological modulator linking these multi-axis changes to endometrial carcinogenesis, with attention to immunological, endocrine, metabolic, microbial–metabolite, oxidative, and barrier-related pathways. Material and Methods: We narratively integrated current evidence on gut and reproductive tract microbiota alterations relevant to endometrial homeostasis, with emphasis on the estrobolome, low-biomass uterine microbial communities, inflammatory and immune signaling, microbial metabolites, and pathways implicated in carcinogenesis. Results: Available data suggest that dysbiosis may influence endometrial carcinogenesis through interconnected endocrine, inflammatory, metabolic, and immune mechanisms. Attention has been given to loss of Lactobacillus dominance, enrichment of anaerobic and pro-inflammatory taxa, altered estrogen recirculation, progesterone resistance, Toll-like receptor activation, NF-κB/STAT3 signaling, COX-2/PGE2 activity, PI3K/AKT/mTOR pathway activation, oxidative stress, macrophage polarization, and impaired natural killer cell surveillance. These alterations may contribute to a permissive microenvironment characterized by persistent inflammation, defective immune control, and disrupted endometrial homeostasis. However, the current literature remains limited by small and heterogeneous cohorts, predominantly cross-sectional designs, contamination risk, and marked methodological variability, particularly in low-biomass uterine samples. Conclusions: Current evidence supports the view that microbiome dysregulation is a context-dependent biological modulator that intersects with endocrine, inflammatory, metabolic, immune, oxidative, and barrier-related pathways relevant to endometrial carcinogenesis. Microbiome dysbiosis should be regarded as a hypothetical contributory factor rather than as an established causal driver. Its near-term translational relevance appears greater for biomarker development and risk stratification than for immediate microbiome-directed therapy. Longitudinal, standardized, and functionally integrated studies are needed to clarify whether microbiome-associated signatures can be translated into clinically meaningful prevention and management strategies in endometrial cancer. Full article

Endometrial cancer is one of the most rapidly increasing gynaecological malignancies worldwide. The clinically adapted molecular classification of endometrial carcinoma, derived from The Cancer Genome Atlas, comprises four major subtypes: POLE-mutated, mismatch repair-deficient, p53-abnormal expression, and no specific molecular profile. Its clinical implementation has improved prognostic stratification, risk assessment, and treatment decision-making in patients with endometrial carcinoma. However, current workflows rely on immunohistochemistry and targeted sequencing, which increase costs, turnaround times, and infrastructure requirements, thereby limiting their universal adoption in routine clinical practice. Recent advances in artificial intelligence (AI), particularly deep learning models capable of predicting molecular features directly from H&E-stained whole-slide images, have emerged as promising tools for precision oncology. In addition to reproducing established molecular classification, these approaches may reveal previously unrecognised biomarker-defined histologic patterns that are difficult to detect using conventional methods. This article synthesises the current evidence on AI-based molecular classification in endometrial carcinoma from a pathologist-centred perspective, emphasising the biological rationale, methodological limitations, and future directions for clinical translation. Full article

Backgroundand Objectives: Endometrial cancer ranks among the most prevalent gynecologic malignancies in high-income countries, with increasing incidence and mortality driven by the global obesity epidemic. Evidence suggests that women with early-stage disease face a greater risk of death from obesity-related comorbidities than from cancer recurrence and that weight reduction is associated with improvements in quality of life and in the long-term burden of obesity-related morbidity and mortality. Minimally invasive (MIS) metabolic/bariatric surgery is the most effective treatment for achieving significant, sustained weight loss and comorbidities resolution/improvement. Advances in MIS (laparoscopic, robotic, and endoscopic) techniques have reduced perioperative morbidity and mortality. Novel pharmacotherapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), have recently received regulatory approval for weight management and ongoing studies are investigating their therapeutic impact on endometrial carcinogenesis and tumor biology. This review synthesizes and critically appraises evidence on metabolic interventions, including innovative bariatric techniques and pharmacologic agents, with the aim of informing their integration into multidisciplinary, risk-adapted management strategies for patients with severe obesity and endometrial cancer. Materials and Methods: A comprehensive review was conducted in accordance with SANRA (Scale for the Assessment of Narrative Review Articles) criteria. Results: Emerging evidence indicates that MIS metabolic/bariatric surgery combined with hysterectomy is feasible and may be integrated into the multidisciplinary management of selected patients with severe obesity and endometrial hyperplasia or carcinoma. GLP-1RAs may modulate both the obesogenic systemic milieu and selected tumor-associated pathways, although definitive clinical evidence of direct antitumor effect and oncologic benefit in endometrial cancer has not been established. Conclusions: Obesity is a modifiable risk factor for endometrial cancer. Metabolic/bariatric interventions represent a promising component of the comprehensive, patient-centered management of this disease. Prospective studies are essential to clarify the association between these interventions and longitudinal oncologic outcomes, the feasibility and potential benefits of combined approaches, and their differential impact according to the molecular classification of endometrial cancers. Although weight reduction is associated with a lower risk of endometrial cancer, a direct improvement in cancer-specific survival has not yet been demonstrated; weight-loss management therefore represents a promising component of care in the severely obese population, and its incorporation into formal guidelines requires confirmation in prospective studies. Full article

Background/Objectives: The 2023 revision of the International Federation of Gynecology and Obstetrics (FIGO) staging system redefines endometrial cancer staging by integrating histopathological and molecular parameters into conventional anatomic assessment. We aimed to quantify stage migration following reclassification from FIGO 2009 to FIGO 2023, to evaluate its impact on survival, and to identify independent prognostic determinants within this restaged cohort. Methods: In this two-center retrospective cohort study, 291 patients with histologically confirmed endometrial cancer were restaged according to both FIGO 2009 and FIGO 2023 systems. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan–Meier method, and independent prognostic determinants were identified through multivariable Cox proportional hazards modeling. Results: Application of FIGO 2023 resulted in stage migration in 32.0% of patients, with 30.6% upstaged and 1.4% downstaged. Upstaged patients demonstrated significantly worse PFS and OS compared with downstaged patients and patients without stage change (p < 0.001 for both). Notably, among patients initially classified as FIGO 2009 stage I, 38% were reassigned to a higher stage and exhibited a marked survival disadvantage (p < 0.001). In multivariable analysis, advanced age and positive surgical margins independently predicted both poorer PFS and OS, while lymphovascular space invasion (LVSI) independently predicted inferior PFS. The association with positive surgical margins, however, likely reflected concurrent advanced-stage disease. Conclusions: The FIGO 2023 staging system results in substantial stage redistribution in endometrial cancer and provides clearer survival discrimination, particularly by identifying previously unrecognized high-risk subgroups within early-stage disease. The significant survival disadvantage observed among upstaged patients indicates that the revised system may more accurately reflect biologically driven risk stratification. However, stage migration was not independently associated with survival after adjustment for its constituent pathological factors. Full article

Background/Objectives: Under the current molecular classification of endometrial cancer, the p53-abnormal group is defined as having the worst prognosis, but the clinicopathological position of low-grade endometrial cancer with p53-abnormal expression relative to high-grade endometrial cancer remains unclear. We previously showed that low-grade endometrial cancer with p53-abnormal expression more closely resembles low-grade endometrial cancer with p53 wild-type expression than high-grade endometrial cancer and that the ERBB2 gene, encoding Human Epidermal Growth Factor Receptor 2 (HER2) protein, is more highly expressed in high-grade endometrial cancer. This study compared HER2 immunohistochemical expression (IHC) among low-grade endometrial cancer with wild-type p53 expression (EC^lop53^wt), low-grade endometrial cancer with p53-abnormal expression (EC^lop53^ab), and high-grade endometrial cancer (EC^hi), in order to characterize EC^lop53^ab. Methods: We retrospectively analyzed 70 endometrial cancer cases treated at Kyushu University Hospital in 1992–2022. Tumors were classified as EC^lop53^wt, EC^lop53^ab, and EC^hi based on histopathology and p53 immunohistochemistry, with EC^hi corresponding to conventional uterine serous carcinoma. HER2 expression was evaluated immunohistochemically using a standardized scoring system (0, 1+, 2+, 3+), and its distribution was compared across the three groups, together with clinicopathological parameters and patient outcomes. Results: EC^hi showed the highest frequency and intensity of HER2 expression, with a substantially larger proportion of HER2 IHC 3+ cases than EC^lop53^wt and EC^lop53^ab (p < 0.0001 and p = 0.0146, respectively). Meanwhile, there was no significant association between EC^lop53^wt and EC^lop53^ab (p = 0.3794). In addition, HER2 IHC 3+ had significant associations with older age (≥60 years) and substantial lymphovascular space invasion (p = 0.0003 and 0.0174, respectively). Conclusions: EC^lop53^ab exhibits HER2 profiles and clinical behavior more similar to EC^lop53^wt, supporting the more nuanced application of molecular classification and HER2-targeted therapy in endometrial cancer. Full article

Endometrial and cervical cancers can recur from subclinical disease not evident on routine surveillance. This narrative review critically evaluates liquid biopsy for minimal residual disease (MRD) assessment and recurrence monitoring. Post-treatment human papillomavirus (HPV) circulating tumor DNA (ctDNA) in cervical cancer has the strongest disease-specific prospective evidence of clinical validity; persistent detection is strongly associated with recurrence, but moderate sensitivity and false-negative results do not support treatment de-escalation on negativity alone. With regard to endometrial cancer, perioperative ctDNA has prognostic support from an 11-study, 1298-patient meta-analysis and additional cohorts, although assay heterogeneity and limited independent replication constrain clinical readiness. Postoperative positivity generally shows stronger associations than preoperative detection. Cervicovaginal and urine DNA-methylation studies provide preliminary evidence for detecting established recurrence, especially local recurrence, but not prospective molecular lead time or clinical utility. Digital PCR, disease-specific fixed panels, tumor-informed assays, and error-corrected sequencing serve distinct settings; broad pan-cancer plasma profiling remains mainly an advanced-disease tool. Circulating tumor cells, extracellular vesicles, microRNAs, tumor-educated platelets, and fragmentomics remain exploratory. Liquid biopsy should remain an investigational adjunct until prospective trials show that acting on molecular findings improves outcomes. Full article

Background/Objectives: The prognostic and predictive values of biomarkers in fertility-sparing management of atypical hyperplasia (AH) and endometrial cancer (EC) remain ill-defined. We aimed to identify the impact of tumour profiles on oncologic and reproductive outcomes to inform clinical decision-making. Methods: We conducted a systematic review and meta-analysis by searching MEDLINE, PubMed, Embase, Cochrane Library, Scopus, Google Scholar, and ClinicalTrials.gov, up to July 2026. We intended to include comparative studies or clinical trials, in English or French, assessing outcomes according to molecular or hormonal profiles in reproductive-aged women diagnosed with AH or EC. The primary outcome was the best overall complete remission (CR). Pooled odds ratios (ORs) were calculated using a random-effects model with logit transformation and restricted maximum likelihood estimation. Risk of bias was assessed using the Newcastle–Ottawa scale (NOS). The study protocol was registered in PROSPERO (CRD42025632885). Results: Eighteen retrospective studies comprising 965 patients were included. No specific molecular profile (NSMP) tumours demonstrated significantly higher odds of CR (OR 2.04, 95% CI 1.33–3.11). p53-abnormal (p53abn) and deficient mismatch repair (dMMR) tumours were significantly less likely to achieve CR compared to NSMP (OR 3.87, 95% CI 1.80–8.29 and OR 2.48, 95% CI 1.44–4.29, respectively). POLE-mutated (POLEmut) tumours showed CR comparable to NSMP (OR 1.39, 95% CI 0.60–3.24). Progesterone receptor (PR) positivity was strongly associated with CR (OR 7.73, 95% CI 2.77–21.63). Conclusions: NSMP and PR-positivity represented a favourable prognosis and potential prediction of CR. POLEmut tumours demonstrated CR rates comparable to NSMP, whereas p53abn and dMMR demonstrated unfavourable outcomes. These findings support a biologically tailored approach to patient selection for fertility-sparing management. Full article

Mismatch repair deficiency (MMRd) is a critical biomarker in endometrial cancer (EC) for prognostication, Lynch syndrome screening, and immunotherapy eligibility. This study aimed to determine the prevalence of MMRd and its correlation with clinicopathological characteristics in EC. This prospective observational cohort included 93 patients with EC undergoing primary surgical treatment, managed as per the European Society of Gynaecological Oncology (ESGO) guidelines. MLH1, PMS2, MSH2, and MSH6 expression was assessed through immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded hysterectomy specimens. Associations between mismatch repair (MMR) status and histology, grade, lymphovascular space invasion (LVSI), myometrial invasion, FIGO 2023 stage, nodal status, recurrence, and survival were analyzed. The median age was 66 years. Most tumors were endometrioid (86%), 29% were grade 3, 45.2% showed deep myometrial invasion, and 23.7% had substantial LVSI. MMRd was identified in 41.9% of cases, with MLH1 and PMS2 loss being most frequent, and was significantly associated with endometrioid histology (p = 0.027) and deep myometrial invasion (p = 0.011). No significant correlations were found with grade, LVSI, FIGO stage, nodal involvement, recurrence, or overall survival. Routine MMR assessment may refine risk stratification and guide individualized treatment decisions. Full article

Background/Objectives: Numerous innovations have changed diagnosis and treatment of endometrial cancer in recent years, with molecular classification being a major factor. Limited data exist on how molecular classification changes in recurrence or metastasis and what effect this may have on therapy. This retrospective study aimed to compare the molecular classification and other histopathological parameters of the primary tumor with those of recurrence or metastasis and to discuss their implications. Methods: A total of 43 patients with primary endometrial cancer and histologically confirmed recurrence treated at the Tuebingen University Women’s Hospital between January 2003 and January 2017 were identified within a cohort of 964 cases. Immunohistochemistry for mismatch-repair status, estrogen receptor, p53 and L1CAM, as well as next-generation sequencing of the POLE genes were performed. Further histopathological and clinical data were collected and statistical analyses were performed. Results: No POLE-mutated patients were found. A higher proportion of high-grade tumors was observed in the recurrence (30% vs. 46%). All p53-mutated patients remained p53-mutated, while a changed molecular profile of the NSMP and MMRd subtypes was observed in nine patients (21%). L1CAM remained stable in 70% of the patients. A change in molecular profile was not associated with altered prognosis. Conclusions: Our study underlines the importance of additional histopathological analysis in case of recurrence or metastasis for individualized therapy planning. Further studies with larger case numbers are necessary to validate our findings. Full article

Objective: Fertility-preserving therapies are a potential option for selected patients with early-stage endometrial cancer and atypical endometrial hyperplasia/endometrial intraepithelial neoplasia. This systematic review aims to evaluate the impact of fertility-preserving strategies according to molecular subtype. Methods: A comprehensive search was conducted in PubMed, Cochrane Library, EMBASE, and Web of Science for English-language studies published until June 2024, investigating fertility-sparing treatments using endocrine therapy in early-stage endometrial cancer, considering molecular classification. The PRISMA checklist was followed, and the protocol was registered in PROSPERO (CRD42025649342). Data on body mass index (BMI), age, and molecular classification (POLE-mutant, non-specific molecular profile [NSMP], p53-abnormal, and mismatch repair deficient [dMMR]) were extracted. The study assessed objective response rates (ORR), pregnancy outcomes, and survival outcomes. Statistical analyses were performed using R software. Results: The search identified 941 articles, and 10 studies with 457 patients were selected for final analysis. Pregnancy outcomes were reported in three studies, whilst all reported ORR data. Baseline median age (dMMR 35 years, POLE-mutant 38.2 years, p53-abnormal 33.9 years, and NSMP 31.6 years) and BMI (dMMR 24.3, POLE-mutant 27.9, p53-abnormal 26.2, and NSMP 29.8) differed by molecular subtype. Aggregated full-term delivery rates from the three studies reporting pregnancy outcomes were 36.4% (4/11) for POLE-mutant, 22.1% (27/122) for NSMP, 14.3% (1/7) for p53-abnormal, and 4.0% (1/25) for dMMR tumours, but statistical comparison was not feasible due to small sample size. Overall response rate was highest in NSMP (87.4%) and POLE-mutant tumours (84.6%), while dMMR (59.3%) and p53-abnormal (58.8%) had significantly lower ORR (compared to NSMP, p < 0.001 and p = 0.03, respectively). Conclusions: These findings support the potential role of molecular classification in refining patient selection for fertility-sparing treatment in early-stage endometrial cancer. Pregnancy-related outcomes should be interpreted with caution given the limited available evidence. Full article

Environmental exposure to pesticides is considered a risk factor for gynecological cancers, contributing to their onset and progression through various mechanisms. This narrative review investigates the role of different pesticides in the development and progression of ovarian, endometrial, and cervical cancers, and provides a comprehensive synthesis of epidemiological findings along with molecular mechanisms, highlighting carcinogenic pathways, conflicting findings, and potential therapeutic implications. Relevant epidemiological and experimental studies published between 2000 and 2025 were identified through searches of major scientific databases. Various pesticides, particularly organochlorines, contribute to gynecological cancers through mechanisms such as estrogen mimicry, DNA damage, oxidative stress, increased pro-inflammatory cytokines, and disruption of cellular signaling pathways. However, most studies found no significant association between certain pesticides, such as Triazines and Atrazine, and gynecological cancers. Furthermore, some pesticides, like Carbendazim, exhibit a dual role; while carcinogenic, they can also serve therapeutic purposes in cancer treatment when utilized with nanotechnology. Overall, pesticide exposure is a significant factor in the development and progression of women’s cancers, although the strength of the evidence varies across pesticide classes. Despite numerous studies, contradictory findings necessitate further research to clarify causal relationships. Full article

Objective: To examine survival outcomes and identify clinicopathological factors associated with survival in patients with advanced-stage endometrial cancer who received neoadjuvant chemotherapy before interval debulking surgery (NACT-IDS). Methods: A single-center retrospective cohort study was conducted of patients who were diagnosed with advanced-stage (2009 FIGO IIIB, IIIC, IV) endometrial cancer (2012–2024) and underwent NACT-IDS. Tumor response to NACT was determined with computed tomography and the RECIST criteria, and demographic, clinicopathologic, perioperative, and tumor molecular features (mismatch repair protein [MMR] status and p53 pattern) were collected from medical chart review. Association between tumor molecular features and response to NACT was determined. Primary endpoints were progression-free and overall survival, analyzed with univariate Cox and stratified Kaplan–Meier analysis. Results: Of 42 consecutive patients (median age of 68 years), the majority (n = 26; 61.9%) had a partial tumor response to NACT, with only five (11.9%) having a complete response, four (9.5%) having stable disease, and seven (16.7%) having progressive disease. Most cases had no residual tumor after IDS (n = 35; 83.3%). MMR protein status was associated with the tumor response to NACT (p = 0.013), but p53 status was not. During follow-up, 24 patients died (57.1%), and 31 (73.8%) died or had disease progression. Tumor response to NACT and resection margin status were associated with progression-free survival in unadjusted analyses, but no covariate adjustment was possible with limited sample size. Conclusions: This study highlights MMR-deficiency, response to NACT, and surgical resection status as clinicopathologic features of interest for future studies of prognostic factors and alternative therapies in advanced-stage endometrial cancer. Full article