Search Results (376)

Background/Objectives: Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) function as effectors in the Hippo pathway and have attracted attention due to their association with tumor formation. Glucose transporter (GLUT) proteins also contribute to the proliferation of cancer cells. In this study, we investigated the effect of YAP/TAZ on GLUT1 expression in endometrial carcinoma, as well as the clinical relevance and prognostic value of YAP/TAZ. Methods: The effects of YAP and TAZ knockdown and YAP overexpression on GLUT1 expression in human endometrial carcinoma-derived HHUA and Ishikawa cells were evaluated using RT-qPCR. In addition, we performed immunohistochemical expression of 100 tissue samples of diagnosed endometrial carcinoma. Based on staining intensity and the percentage of positively stained tumor cells, the immunoreactivity score was calculated, which ranged from 0 to 12. Results: YAP/TAZ were identified as important factors in the regulation of GLUT1 expression in HHUA and Ishikawa cells. In addition, a significant correlation (progression-free survival p < 0.05) was observed between TAZ and GLUT1 expression in tissues from endometrial carcinoma patients, and nuclear expression of TAZ was associated with poor prognosis (p < 0.05). Conclusions: YAP/TAZ promote tumor growth via GLUT1. Therapeutic targeting of YAP/TAZ could therefore be useful in the development of future treatments. Full article

Rationale: The ProMisE molecular classification improves risk assessment in endometrial cancer (EC), but 3–11% of cases exhibit overlapping molecular features, complicating clinical decisions. We analyzed the prevalence and clinicopathological profiles of multiple-classifier ECs in a large Polish cohort. Methods: In this retrospective study (2022–2025), 1075 ECs from four institutions were classified by MMR and p53 immunohistochemistry and POLE exon sequencing. Tumors showing ≥2 molecular features (e.g., MMRd–p53abn, POLEmut–p53abn) were categorized as multiple-classifier ECs. Results: Multiple-classifier ECs comprised 6.9% (74/1075), with MMRd–p53abn (3.9%) being most common. These tumors exhibited more aggressive features vs. MMRd-only: G3 (28.57% vs. 11.79%, p = 0.002), non-endometrioid histology (11.9% vs. 2.85%, p = 0.018), and high–intermediate/high-risk (HIR/HR) groups (59.52% vs. 37.80%, p = 0.001). POLEmut–p53abn (N = 4) and POLEmut–MMRd–p53abn (N = 10) tumors showed advanced stages (75% and 40% FIGO III–IV, respectively), in contrast to classical POLEmut tumors (6.7% FIGO III–IV), and higher rates of nodal metastases. Conclusions: Co-occurrence of molecular classifiers, including triple-classifier tumors, correlates with more adverse profiles and may undermine current stratification paradigms. This study emphasizes the need to further investigate and refine molecular risk models to account for overlapping profiles. Full article

Endometrial carcinoma (EC) is the most common gynaecological malignancy in developed nations, exhibiting significant molecular heterogeneity that impacts prognosis and treatment response, particularly in advanced or recurrent settings. Traditional classification is increasingly supplemented by molecular subtyping (POLE-ultramutated, MSI-high/dMMR, NSMP, p53-mutated/CNH), which provides crucial prognostic information and predicts benefit from immunotherapy. This review summarizes the landscape of predictive biomarkers for immune checkpoint inhibitor (ICI) therapy in EC, emphasizing a new therapeutic scenario for advanced and recurrent EC. Mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H), leading to high tumor mutational burden (TMB) and increased neoantigen production, is the most established predictor, resulting in FDA approvals for pembrolizumab and dostarlimab in this subgroup. POLE mutations also confer hypermutation and high immunogenicity, predicting a favorable ICI response. Other biomarkers, including PD-L1 expression and TMB, show variable correlation with response and require further standardization. The tumor immune microenvironment, including tumor-infiltrating lymphocytes (TILs), also influences treatment outcomes. Clinical trials have demonstrated significant survival benefits for ICIs combined with chemotherapy (e.g., dostarlimab/pembrolizumab + carboplatin/paclitaxel) in first-line settings, especially for dMMR/MSI-H EC, and for ICI combinations with targeted agents (e.g., lenvatinib + pembrolizumab) in previously treated patients. Integrating molecular classification and validated biomarkers is essential for optimizing patient selection and developing personalized immunotherapy strategies for EC. Full article

Background: The glucocorticoid receptor (GR) regulates the transcription of thousands of genes. In cancer, both oncogenic and tumor suppressive roles of GR have been proposed. Methods: A tissue microarray containing 18,527 samples from 147 tumor (sub-)types and 608 samples from 76 normal tissue types was analyzed for GR expression by immunohistochemistry. Results: GR positivity was found in 76.4% of 14,349 interpretable cancers, including 18.5% with weak, 19.6% with moderate, and 38.3% with strong positivity. GR positivity appeared in all 147 tumor types, with at least one strongly positive tumor in 136 types. Of out tumor entities, 77 of the 147 showed GR positivity in 100% of the cases analyzed. Only six tumor types had less than 50% GR-positive cases, including adenomas with low-/high-grade dysplasia (32.5%/21.7%), adenocarcinomas (17%) and neuroendocrine carcinomas (45.5%) of the colorectum, endometrial carcinomas (25.6%), and rhabdoid tumors (25%). Reduced GR staining was associated with grade progression in pTa (p < 0.0001) and with nodal metastasis in pT2-4 (p = 0.0051) urothelial bladder carcinoma, advanced pT stage (p = 0.0006) in breast carcinomas of no special type (NST), and high grade (p = 0.0066), advanced pT stage (p < 0.0001), and distant metastasis (p = 0.0081) in clear cell renal cell carcinoma. GR expression was unrelated to clinico-pathological parameters in gastric, pancreatic, and colorectal adenocarcinoma, and in serous high-grade carcinoma of the ovary. Conclusions: GR expression is frequent across all cancer types. Associations between reduced GR expression and unfavorable tumor features in certain cancers suggest that the functional importance of GR-regulated genes in cancer progression depends on the cell of tumor origin. Full article

Background: Following the results of the Laparoscopic Approach to Carcinoma of the Cervix (LACC) trial, doubts have arisen about the safety of laparoscopy in the treatment of endometrial cancer. Methods: A retrospective multicenter cohort study which included all endometrial cancer (EC) patients who underwent a hysterectomy in Emilia Romagna hospitals from 2000 to 2019. All cases were revised and classified according to the 2009 International Federation of Gynaecology and Obstetrics (FIGO) staging system. The different impacts of the surgical approach on survival were stratified according to the recurrence risk from the 2016 European Society for Medical Oncology (ESMO)–European Society of Gynaecological Oncology (ESGO) classification system. The clinical characteristics and oncological outcome of patients treated by laparoscopy were compared with those treated by laparotomy. Results: A total of 2402 EC patients were included in the study. The use of laparoscopy has increased over the years, reaching 81% of procedures in 2019. Laparoscopy reduced complications and hospital stay. Laparoscopy was preferred to treat low, intermediate, and intermediate/high-risk patients. Laparoscopy showed no adverse effects on overall survival (OS) in any recurrence risk class. Particularly in high-risk EC patients, laparoscopy was associated with an increased OS in comparison with women treated by laparotomy regardless of the use of adjuvant therapy. Conclusions: Laparoscopy should always be chosen to treat EC of any risk class. The goal is to ensure correct treatment and oncological safety regardless of the surgical approach. Full article

Background/Objectives: Osteopontin (OPN) is a 34 kDa protein that is extensively phosphorylated and rich in aspartic acid, produced by a single-copy gene, and altered by post-translational processes. In several diseases, OPN has been discovered to play a direct role in immunological and inflammatory responses. It is also important in kidney stone disease, preeclampsia, cardiovascular disease, endometriosis, and cancer, among other pathological conditions. It is a crucial extracellular matrix molecule involved in oncology, due to its ability to bridge the gap between inflammation and carcinogenesis. Methods: Our systematic review has as PICO “Does Osteopontin have possible etiological and prognostic correlations in patients affected by endometrial carcinoma?” Based on online data collected from PubMed, Scholar, Embase, Scopus, and other sources, a preliminary analysis was conducted. A keyword search for “Osteopontin” AND “tumors”, “endometrial cancer”, and other related terms was used to identify the publications. The relevance of scientific research was used to select articles in English. Results: For our systematic review, the citation search yielded nine articles on the topic. At the endometrial level, OPN plays a role in a variety of biological processes, including angiogenesis, metastasis, altered tissue remodeling, immunological responses, cell adhesion, and migration. Conclusions: With established direct correlations and a potential role in the assessment of the diagnosis and prognosis of the disease, OPN participates in endometrial cancer, drawing more and more attention from researchers. Full article

Background/Objectives: Endometrial cancer (EC) is the sixth most common cancer among women worldwide, and its global incidence has significantly increased over the past three decades. Despite its substantial burden, comprehensive reviews of EC-related research remain limited. This study employs topic modeling to analyze and classify recent research trends in EC. Methods: We identified studies related to endometrial carcinoma published between 2019 and 2023 in PubMed, Web of Science, and the Cochrane Library. The search was conducted using the following terms: endometr* AND (neoplasm* OR cancer* OR carcinoma*) NOT endometriosis. Word clouds were constructed and topic modeling was performed to analyze research activity. Results: A total of 2188 studies were selected, and 11,552 terms were extracted. High-frequency and TF-IDF-weighted keywords included ‘cancer’, ‘risk’, ‘survival’, ‘stage’, ‘tumor’, ‘surgery’, and ‘OS.’ Topic modeling analysis identified ten clusters, categorized as follows: ‘Gynecologic cancer’, ‘Surgical staging’, ‘Therapeutic efficacy’, ‘Diagnosis’, ‘Surgical management’, ‘Multimodal treatment’, ‘Molecular treatment’, ‘Risk factors’, ‘Survival’, and ‘Hormonal regulation.’ Conclusions: This study highlights that recent research on EC has primarily focused on surgical decision making, outcome prediction, and patient survival. Future studies should place greater emphasis on multimodal treatment and prevention—particularly through the identification of risk factors—as well as on improving patients’ quality of life. Full article

Endometrial carcinosarcoma (ECS) is a rare and aggressive histological subtype of endometrial cancer that is associated with a dismal prognosis. It is a biphasic metaplastic carcinoma with a monoclonal origin comprising epithelial and mesenchymal components. The ECS originates from the epithelial components of the tumor, which undergoes an epithelial-to-mesenchymal transition. Approximately half of patients are diagnosed at the early stage of the disease, whereas the other half are diagnosed at the advanced stage. More than one-third of women present with metastatic lymph nodes, and approximately 10% will have distant metastases. Therefore, ECS is the deadliest type of endometrial cancer compared to other high-grade endometrial carcinomas. Surgical resection with adjuvant therapy remains the standard of care in most cases. The rarity of this disease hinders conducting prospective clinical trials to establish the optimal treatment regimens and increase overall survival. There are no specific guidelines for managing these rare and aggressive tumors despite the increasing interest in ECS in the gynecologic oncology community. The present review focuses on all new insights into ECS regarding its epidemiology, pathology, prognosis, and treatment. Furthermore, the molecular characteristics and new treatment regimens for primary (early and advanced stages) and recurrent ECS are discussed in detail. Full article

Background/Objectives: High-grade endometrial cancer, including non-endometrioid and grade 3 endometrioid histologies, is associated with poor prognosis despite early-stage diagnosis. This study assessed the prognosis of early-stage high-grade endometrial cancer, identified prognostic factors, and evaluated the optimal candidates for adjuvant therapy. Methods: We retrospectively analyzed 106 patients with 2018 FIGO stage I–II high-grade endometrial cancer who underwent hysterectomies between 2008 and 2022. Adjuvant therapy was determined by a multidisciplinary team. Survival outcomes were evaluated using the Kaplan–Meier method and Cox regression model. Results: Of 106 patients, 60 had non-endometrioid, and 46 had grade 3 endometrioid carcinoma; 69 (65.1%) received adjuvant therapy. After a median follow-up of 48.8 months, 37 patients experienced disease progression, and 21 died. Non-endometrioid histology was significantly associated with worse overall survival (p = 0.002). Lack of lymph node dissection, deeper invasion, and the omission of adjuvant therapy were additional adverse prognostic factors. Adjuvant therapy improved the overall survival (p = 0.009), disease-free survival (p = 0.021), and locoregional recurrence-free survival (p = 0.034) in patients with one or two risk factors. Conclusions: Non-endometrioid histology, deep invasion, and the lack of lymph node dissection are associated with worse survival in early-stage high-grade endometrial cancer. Adjuvant therapy should be considered in patients with these risk factors. Full article

Malignancies of the female upper reproductive tract, especially endometrial and ovarian cancers, generate a significant burden for women worldwide. The possible etiopathogenetic role of chronic human papillomavirus (HPV) infection in the carcinogenesis of the female upper genital tract is neither clearly established not completely understood. Therefore, we performed a literature review, using the PubMed and SCOPUS electronic databases, of the prevalence of HPV DNA in endometrial, primary fallopian tube, ovarian, and primary peritoneal cancers, as well as uterine sarcomas. The present investigation covered 35 studies from different countries on various continents. Overall, the prevalence of HPV was approximately 15% in all the above cancers. HPV DNA was isolated from 11%, 0%, 0%, and 14% of endometrial carcinomas, uterine sarcomas, primary fallopian tube cancers, and ovarian malignant neoplasms, respectively. No relevant studies on primary peritoneal cancers were retrieved. The predominant HPV strain from tumors of the upper female reproductive tract, regardless of the tumor site, was HPV-16, followed by HPV-18. The HPV DNA identified was exclusively from subtypes HPV-6, HPV-11, HPV-16, HPV-18, and HPV-33, which are responsible for the development of not only cervical cancer, but also condylomata acuminata. The findings of the present review indicate that HPV vaccination might prove to be a useful strategy in the prevention of HPV-related carcinomas of the upper genital tract in women. Full article

In 2023, the Polish Society of Gynecologic Oncology (PSGO) published clinical recommendations for the diagnosis, treatment, and care of women with endometrial cancer (EC), developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. A 2025 update was initiated in response to new evidence, particularly regarding systemic therapies for metastatic, advanced, or recurrent EC, and the introduction of an updated FIGO classification. A targeted literature review identified relevant phase III clinical trials and systematic reviews, including RUBY, GY-018, AtTend, and DUO-E. These trials were critically assessed by an Expert Panel in accordance with the AGREE II methodology. Updated recommendations were formulated based on this evidence, with a comparative analysis of the old and new FIGO staging systems and visual updates to treatment pathways. Key changes include the addition of immunotherapy (I/O) plus chemotherapy (CHTH) as first-line treatment for all molecular subtypes of high-grade endometrioid and non-endometrioid carcinomas, replacing chemotherapy alone. For MMRp-positive cases, the 2025 version introduces the use of Olaparib alongside Durvalumab and CHTH. HER2-positive MMRp serous carcinoma remains eligible for trastuzumab in combination with CHTH. Second-line treatment guidance remains unchanged for patients who did not receive I/O plus CHTH initially. However, options for those previously treated with this combination are still under evaluation. This update ensures alignment with the latest international standards and reinforces evidence-based, personalized care for EC patients. Full article

(1) Background and Objectives: Endometriosis is defined as the presence of endometrial glands and stroma outside the uterine cavity. It affects 5–15% of women of reproductive age. Ovarian cancer develops in approximately 1% of patients with endometriosis. Prediction of those with endometriosis who will develop ovarian cancer is among the current research topics. (2) Materials and Methods: With this study, we aimed to reveal the role of miRNA 200b and miRNA 21 in endometriosis-associated ovarian carcinoma (EAOC). Thirteen patients diagnosed as having EAOC between 2015 and 2023 were included, with their endometriosis and eutopic endometrium tissues (Group 3: 13 patients, 39 tissue samples). Two separate groups were then detected to compare with these cases: Group 2 composed of tuba-ovarian endometriosis with its eutopic endometrium (10 patients, 20 tissue samples) and Group 1 composed of eutopic endometrium only (10 patients, 10 tissue samples). The foci marked on H&E sections were determined from the area on the relevant paraffin blocks and small tissue samples were taken in tubes to be studied with real-time PCR. (3) Results: No significant difference was detected for miRNA 21 and miRNA 200b expression levels among eutopic endometrium, endometriosis, and cancer foci in Group 3. However, miRNA 21 and miRNA 200b expression levels in the eutopic endometrial tissue of cases with ovarian cancer were significantly higher than in the eutopic endometrial tissues of cases with (Group 2) and without endometriosis (Group 1). (4) Conclusions: This study suggests that increased miRNA 200b and miRNA 21 expression levels detected in eutopic endometrial tissue of patients with endometriosis may contribute to identifying cases that may develop EAOC. Full article

Objective: Accurate preoperative differentiation between benign endometrial conditions and malignancies is essential for guiding therapeutic interventions. However, high-quality evidence regarding the diagnostic accuracy of endometrial sampling techniques remains insufficient. This study aimed to evaluate the diagnostic efficiency of hysteroscopically directed biopsy, Pipelle suction curettage, and dilatation and curettage (D&C) for detecting endometrial hyperplasia or carcinoma in premenopausal women and to identify associated risk factors. Methods: A retrospective single-center cohort analysis was conducted on 2054 premenopausal women. Demographic, clinical, and obstetric data, along with biopsy techniques and histopathological findings, were recorded. Diagnostic accuracy of biopsy methods was compared against definitive surgical pathology. Results: The prevalence of endometrial hyperplasia and carcinoma was 5.6% and 1.0%, respectively. Hysteroscopically directed biopsy demonstrated superior diagnostic accuracy (AUC 0.957) compared to D&C (AUC 0.909) and Pipelle suction curettage (AUC 0.858). Sensitivity was highest for hysteroscopically directed biopsy (91.3%), followed by D&C (82.0%) and Pipelle suction curettage (71.7%), while specificity remained excellent across all methods (p < 0.001). Elevated BMI increased the risk of hyperplasia or carcinoma by 1.05 times per unit increase (OR = 1.054, p = 0.005), while hypertension nearly doubled the risk (OR = 1.99, p = 0.009). Multiparity showed protective effects, reducing risk with each additional delivery (OR = 0.877, p = 0.029). Conclusions: Hysteroscopically directed biopsy provides superior diagnostic accuracy for detecting endometrial hyperplasia and carcinoma in premenopausal women. Hypertension and elevated BMI increase risk, while multiparity offers protective benefits. Full article

Background: Endometrial carcinoma (EC) is the most common gynecological malignancy, with increasing incidence contributing to a significant global health burden. Despite recent advancements, the molecular mechanisms underlying EC progression remain insufficiently understood, limiting the development of targeted therapies. This study aims to investigate the role of nucleoside diphosphate-linked moiety X motif 5 (NUDT5) in EC and evaluate its potential as a biomarker and therapeutic target. Methods: This study analyzed gene expression data from The Cancer Genome Atlas and performed tissue microarray validation to assess NUDT5 expression in EC samples. Immunohistochemistry was used to evaluate NUDT5 protein levels and their correlation with clinicopathological features. Functional assays, including cell proliferation, migration, invasion, and apoptosis analysis, were conducted to determine the oncogenic effects of NUDT5 in vitro. Weighted gene co-expression network analysis (WGCNA) and experimental validation were performed to explore the impact of NUDT5 on the PI3K-AKT signaling pathway, while tumor growth assays in xenograft models assessed the therapeutic potential of NUDT5 inhibition in vivo. Results: NUDT5 was significantly overexpressed in EC tissues and correlated with advanced histological grade and poor prognosis. Functional experiments demonstrated that NUDT5 promotes cell proliferation, migration, and invasion while inhibiting apoptosis. Mechanistically, NUDT5 activated the PI3K-AKT pathway, contributing to tumor progression. In vivo, NUDT5 knockdown suppressed tumor growth. Conclusions: These findings suggest that NUDT5 functions as an oncogene in EC, serving as a potential diagnostic and prognostic biomarker. Targeting NUDT5 may provide a novel therapeutic strategy for EC management. Full article