Search Results (184)

Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Risk factors for EC include metabolic alterations (obesity, metabolic syndrome, insulin resistance), hormonal imbalance, age at menopause, reproductive factors, and inherited conditions, such as Lynch syndrome. For the inherited forms, several genes had been implicated in EC occurrence and development, such as POLE, MLH1, TP53, PTEN, PIK3CA, PIK3R1, CTNNB1, ARID1A, PPP2R1A, and FBXW7, all mutated at high frequency in EC patients. However, gene function impairment is not necessarily caused by mutations in the coding sequence of these and other genes. Gene function alteration may also occur through post-transcriptional control of messenger RNA translation, frequently caused by microRNA action, but transcriptional impairment also has a profound impact. Here, we review how chromatin modifications change the expression of genes whose impaired function is directly related to EC etiopathogenesis. Chromatin modification plays a central role in EC. The modification of chromatin structure alters the accessibility of genes to transcription factors and other regulatory proteins, thus altering the intracellular protein amount. Thus, DNA structural alterations may impair gene function as profoundly as mutations in the coding sequences. Hence, its central importance is in the diagnostic and prognostic evaluation of EC patients, with the caveat that chromatin alteration is often difficult to identify and needs investigations that are specific and not broadly used in common clinical practice. The different phases of the healthy endometrium menstrual cycle are characterized by differential gene expression, which, in turn, is also regulated through epigenetic mechanisms involving DNA methylation, histone post-translational modifications, and non-coding RNA action. From a medicolegal and policy-making perspective, the implications of using epigenetics in cancer care are briefly explored as well. Epigenetics in endometrial cancer is not only a topic of biomedical interest but also a crossroads between science, ethics, law, and public health, requiring integrated approaches and careful regulation. Full article

Background: Endometrial cancer (EC) is the sixth most common cancer among women globally, with an estimated 420,000 new cases diagnosed annually. Methods: This study comprised patients with endometrial cancer (EC) (n = 17), hyperplasia (HY) (n = 17), and controls (CO) (n = 20). Tissue was collected from the endometrium of all 54 patients, including patients with HY, EC, and CO, who underwent total hysterectomy. EC and HY diagnoses were confirmed based on histological examination. Untargeted metabolomics profiling was conducted using LC-HRMS. The partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models were used for univariate and multivariate statistical analysis. The fitness of the model (R2Y) and predictive ability (Q2) were used to create OPLS-DA models. ROC analysis was carried out, followed by network analysis using Ingenuity Pathway Analysis. Results: The top metabolites that can discriminate EC and HY from CO were identified. This revealed a decrease in the levels of the lipid species, specifically phosphatidic acid (PA) (PA (14:1/14:0), PA(10:0/17:0), PA(18:1-O(12,13)/12:0)), PG(a-13:0/a-13:0), ganglioside GA1 (d18:1/18:1), PS(14:1/14:0), TG(20:0/18:4/14:1), and CDP-DG(PGF2alpha/18:2), while the levels of 3-Dehydro-L-gulonate, Uridine diphosphate-N-acetylglucosamine, ganglioside GT2 (d18:1/14:0), gamma-glutamyl glutamic acid and oxidized glutathione were increased in cases of EC and HY as compared to CO. Bioinformatics analysis, specifically using Ingenuity Pathway Analysis (IPA), revealed distinct pathway enrichments for EC and HY. For EC, the most highly scored pathways were associated with cell-to-cell signaling and interaction, skeletal and muscular system development and function, and small-molecule biochemistry. In contrast, HY cases showed the highest scoring pathways related to inflammatory disease, inflammatory response, and organismal injury and abnormalities. Conclusions: Developing sensitive biomarkers could improve diagnosis and guide treatment decisions, particularly in identifying which patients with HY may safely avoid hysterectomy and be managed with hormonal therapy. Full article

Background: Endometrial cancer (EC) remains a major gynecologic malignancy with limited biomarkers for risk stratification. While killer cell lectin-like receptor G2 (KLRG2) exhibits oncogenic properties in other cancers, its clinical significance and mechanistic roles in EC are unknown. This study aims to systematically characterize KLRG2 expression in EC, evaluate its prognostic significance, decipher underlying molecular mechanisms, and explore its role in tumor immune microenvironment regulation. Methods: We performed integrated multi-omics analyses using TCGA-UCEC (n = 552), GTEx, and GEO cohorts (GSE106191), complemented by qPCR validation (14 EC vs. 14 normal samples). Prognostic models were constructed via Cox regression and time-dependent ROC analysis. Epigenetic regulation was assessed through methylation profiling (UALCAN/MethSurv), and immune correlations were evaluated using TIMER/ESTIMATE algorithms. Results: KLRG2 was significantly overexpressed in EC tissues compared to normal endometrium (p < 0.001), validated by immunohistochemistry and qPCR. High KLRG2 expression independently predicted worse overall survival (HR = 3.08, 95% CI = 1.92–4.96) and progression-free interval (HR = 1.98, 95% CI = 1.37–2.87). Furthermore, elevated KLRG2 levels were significantly associated with advanced-stage disease (p < 0.001), deep myometrial invasion (p < 0.05), and high-grade histology (p < 0.001). Mechanistically, promoter hypomethylation was associated with KLRG2 overexpression (p < 0.001), while hypermethylation at three CpG sites (cg04915254, cg04520485, cg23104233) correlated with poor prognosis. Functional enrichment linked KLRG2 to cell cycle checkpoints and G Protein-Coupled Receptor signaling. Immune profiling revealed cytotoxic lymphocyte depletion (CD8+ T cells: Spearman’s ρ = −0.247, p < 0.001; NK CD56bright cells: Spearman’s ρ = −0.276, p < 0.001) and Th2 polarization (Spearman’s ρ = 0.117, p = 0.006). Conclusions: This comprehensive EC study establishes KLRG2 as a dual diagnostic/prognostic biomarker and immunomodulatory target. These findings provide a rationale for developing KLRG2-directed therapies to counteract tumor-intrinsic proliferation and microenvironmental immune suppression. Future single-cell analyses are warranted to dissect KLRG2-mediated tumor-immune crosstalk. 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

Background/Objectives: This study aimed to investigate oncologic and obstetrical outcomes of patients conservatively treated for atypical hyperplasia (AH), endometrial intraepithelial neoplasm (EIN), and early endometrial cancer (EC), as well as factors that influence these outcomes. Methods: This study included 87 women conservatively treated due to AH/EIN and well-differentiated endometrioid EC confined only to the endometrium during past 10 years. Therapy type, course, and duration were registered. The response totherapy after 12 months (remission vs. disease persisting or progressing) was considered as the oncologic outcome. All attempted and achieved pregnancies, along with conception method, gestational week, and delivery type, were recorded. The obstetrical outcomes were classified as adverse (miscarriage) or successful (healthy child). Results: All patients received LNG-IUD along with GnRHa and, if indicated, metformin. Complete remission was achieved in 74.7% of patients. The disease was persisting in 17.2% and progressing in 3.5% of patients, while recurrence was registered in 4.6% of patients. Radical surgery during follow-up was indicated in 15% of patients due to condition deterioration. Pregnancy was attempted by 29.9% of patients, out of which nine succeeded (34.6%). There were two early miscarriages, while the remaining seven pregnancies ended in a term delivery of a healthy child, mostly by planned cesarean section. The only predictor of long-term disease remission was malignancy-free control histological findings. Better therapy response and achieving remission in shorter time were predictors of good obstetrical outcome. Conclusions: This study proved the efficacy and safety of current protocols for AH/EIN/EC conservative treatment and indicated that adequate early (6-month) response totherapy has the most importance for long-term remission and pregnancy achievement. Full article

Endometriosis, a complex inflammatory disease, affects a significant proportion of women of reproductive age, approximately 10–15%. The disease involves the growth of endometrial glands and stroma outside the uterine cavity, leading to tissue remodeling and fibrosis. Hormonal imbalances, accompanied by local and general inflammation and pain, are key features of endometriosis. Endometriotic lesions are associated with the overproduction of cytokines, metalloproteinases, prostaglandins, reactive oxygen radicals, and extracellular vesicles. Genetic predisposition and cytokine gene polymorphisms have been documented. Macrophages, dendritic cells, mast cells, Th1 in the early phase, Th2 in the late phase, and T regulatory cells play a crucial role in endometriosis. Reduced NK cell function and impaired immune vigilance contribute to endometrial growth. The strong inflammatory condition of the endometrium poses a barrier to the proper implantation of the zygote, contributing to the infertility of these patients. Cytokines from various cell types vary with the severity of the disease. The role of microbiota in endometriosis is still under study. Endometriosis is associated with autoimmunity and ovarian cancer. Hormonal treatments and surgery are commonly used; however, recent interest focuses on anti-inflammatory and immunomodulatory therapies, including cytokine and anti-cytokine antibodies. Modulating the immune response has proven critical; however, more research is needed to optimize treatment for these patients. Full article

Endometriosis is a gynecological disease characterized by the presence of endometrium-like cells located outside the uterus. The most widely accepted theory for endometriosis development, retrograde menstruation, does not account for extra-pelvic lesions or ones found on other organs in the peritoneal cavity. Similar to ovarian cancer, endometriosis cells can interact with the mesothelial cells of the peritoneal cavity. In ovarian cancer metastasis, ovarian cancer cell spheroids attach and push away the mesothelial cells lining the peritoneal cavity, clearing the mesothelial layer. Since endometriosis cells are known to interact with the mesothelium, we hypothesized that endometriosis cells would be able to form spheroids capable of undergoing mesothelial clearance. To test this, we designed an in vitro mesothelial clearance assay using endometriosis spheroids and a mesothelial cell monolayer. Our results demonstrate that normal and endometriotic epithelial cell spheroids can perform mesothelial clearance similar to ovarian cancer spheroids, though normal endometrial cells do not clear as well as endometriosis cells. Additionally, we demonstrated that our mesothelial clearance assay can test potential pharmacological therapies for endometriosis prior to clinical trials. These results give insight into the development of endometriosis lesions, but further research is needed to determine the mechanisms behind mesothelial clearance in endometriosis. Full article

Background/Objectives: To evaluate the association between endometrial tissue stiffness, as measured by shear wave elastography (SWE), and the presence of specific gene mutations in patients diagnosed with endometrial cancer. Methods: Peripheral blood samples were collected for DNA extraction and next-generation sequencing (NGS) to identify gene mutations. Preoperative SWE was performed to measure endometrial stiffness, with values expressed in kilopascals (kPa). Statistical analyses were conducted to assess the correlation between SWE measurements and genetic findings. Results: Genetic mutations were detected in 66% (n = 31) of cases, with TTN, PLEC, and PRSS1 being the most frequently mutated genes. The median SWE measurement was 36.5 kPa (range: 19.1–70.4 kPa). No statistically significant correlation was found between SWE values and the presence of gene mutations (p > 0.05). Cases with metastasis exhibited higher median SWE values (40.1 kPa) compared to non-metastatic cases (34.7 kPa), though this difference was not statistically significant. Conclusions: While no significant association was observed between endometrial stiffness and specific gene mutations, higher SWE values in metastatic cases suggest that increased tissue stiffness may be linked to tumor aggressiveness. Further large-scale studies are warranted to validate these findings and explore the potential of SWE as a non-invasive tool in assessing endometrial cancer characteristics. Full article

Background/Objectives: Despite advancements in treatment options, endometrial cancer remains a significant threat to women, underscoring the importance of early detection of atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN), the widely accepted histological precursor to endometrial carcinoma. Even with refinements in morphological criteria for the diagnosis of AH/EIN, accurate diagnosis remains challenging for pathologists, particularly in cases with secretory changes. Morphological alterations resulting from secretory-related changes further complicate the application of diagnostic criteria, emphasizing the need for reliable biomarkers. Previous studies have demonstrated that a panel consisting of three immunohistochemical markers, PAX2, PTEN, and β-catenin, can be effectively utilized for the identification of AH/EIN in various non-secretory scenarios. Methods: In this study, a total of 69 AH/EIN within secretory endometrium were analyzed using this panel. Benign interval endometrium (n = 57) and secretory phase endometrium (n = 71) were also analyzed for PAX2, PTEN, and β-catenin expression as controls. Results: The 3-marker panel successfully identified 93% of secretory AH/EIN, comparable to its performance in identifying non-secretory bona fide AH/EIN (92.8%) and AH/EIN within endometrial polyps (92.4%). Of note, β-catenin expression in benign interval endometrium commonly displayed weak nuclear staining (67%), which could pose a diagnostic pitfall when using the 3-marker panel. Overall, the results demonstrate the diagnostic utility of the 3-marker panel in clinical practice in identifying AH/EIN within challenging secretory phase endometrium cases. Conclusions: Combined with previous research highlighting its effectiveness in other challenging contexts—such as AH/EIN in polyps, small-sized EIN (subdiagnostic EIN), and progestin-treated EIN—this study provides strong evidence supporting the panel’s broad applicability in resolving major diagnostic challenges related to the precise diagnosis of AH/EIN. Full article

Endometrial cancer (EC) is the fourth-most frequent cancer among the female population and a leading cause of death. Multiple factors are susceptible to causing tumorigenesis, including obesity, lack of physical activity, diabetes mellitus, high concentration of estrogen during menopause, unopposed exposure to estrogen, duration of menses, nulliparity and infertility. Human papillomavirus (HPV) is a double-stranded DNA virus, with certain genotypes exclusively human. HPV plays a major role in some cancers (cervical cancer, head and neck cancer, lung cancer, and anogenital cancers). Given the intricate correlation between HPV and cervical cancer, the scientific community conjectured that HPV may be implicated in the carcinogenesis of the endometrium. In this review, we will direct our interest towards previous studies that focused on the expression of HPV on EC samples and cover how both conditions might connect to each other. Full article

Background: Ultrasonography is essential for diagnosing endometrial pathologies, such as hyperplasia, polyps, and endometrial cancer. The International Endometrial Tumor Analysis (IETA) group provides guidelines for using ultrasound to assess endometrial thickness, texture, and irregularities, aiding in the diagnosis of these conditions. The aim of this study was to evaluate the utility of various endometrial morphological features, as assessed by gray-scale ultrasound, and endometrial vascular features, as assessed by power Doppler ultrasound, in differentiating benign and malignant endometrial pathologies. A secondary objective was to compare the effectiveness of these ultrasound techniques in assessing myometrial invasion. Methods: A total of 162 women, both pre- and postmenopausal, with or without abnormal vaginal bleeding were enrolled in a prospective study. All participants underwent transvaginal gray-scale and color Doppler ultrasound examinations, conducted by examiners with over 15 years of experience in gynecological ultrasonography. Endometrial morphology and vascularity characteristics were evaluated based on the IETA group criteria, which include parameters such as endometrial uniformity, echogenicity, the three-layer pattern, regularity of the endometrial–myometrial border, Doppler color score, and vascular pattern (single dominant vessel with or without branching, multiple vessels with focal or multifocal origin, scattered vessels, color splashes, and circular flow). Sonographic findings were compared with histopathological results for comprehensive assessment. Results: The mean age of the study population was 56.46 ± 10.84 years, with a range from 36 to 88 years. Approximately 53.08% of the subjects were postmenopausal. The mean endometrial thickness, as measured by transvaginal ultrasonography, was 18.02 ± 10.94 mm with a range of 5 to 64 mm (p = 0.028), and it was found to be a significant predictor of endometrial malignancy. The AUC for the ROC analysis was 0.682 (95% CI: 0.452–0.912), with a cut-off threshold of 26 mm, yielding a sensitivity of 62.5% and a specificity of 89%. Vascularization was absent in 68.4% of patients with polyps. Among the cases with submucosal myomas, 80% exhibited a circular flow pattern. Malignant lesions were identified in 22.84% of the cases. Subjective ultrasound assessment of myometrial invasion, categorized as <50% or ≥50%, corresponded in all cases with the histopathological evaluation, demonstrating the effectiveness of ultrasound in evaluating myometrial invasion in endometrial cancer. Conclusions: In this study, cystic atrophic endometrium was identified as the most prevalent cause of postmenopausal bleeding. The most significant ultrasound parameters for predicting malignancy included heterogeneous endometrial echogenicity, increased endometrial thickness, and the presence of multiple vessels with multifocal origins or scattered vascular patterns. Additionally, color Doppler blood flow mapping was demonstrated to be an effective diagnostic tool for the differential diagnosis of benign intrauterine focal lesions. Full article

Introduction: Endometrial cancer is the most common malignancy of the female genital tract in high-income countries. A prompt diagnosis of this condition is of utmost importance in ensuring that patients receive the best treatment strategy. The new FIGO 2023 molecular classification of endometrial cancer radically changes the current landscape of this disease’s treatment and follow-up. Among the various diagnostic techniques used to identify endometrial lesions, hysteroscopy and vacuum biopsy techniques are the most employed in clinical practice. The aim of this systematic literature review is to compare the efficacy, sensitivity, specificity, and safety of these methods when employed to diagnose endometrial cancer, as well as to assess the feasibility of endometrial cancer molecular profiling on biopsy specimens. Methods: A systematic literature search of studies evaluating hysteroscopy and VABRA biopsy performance in diagnosing endometrial cancer was conducted using the main online databases (PubMed, EMBase, Cochrane Library). An additional literature search was conducted, focusing on the feasibility of endometrial cancer molecular profiling on hysteroscopic biopsy and VABRA samples, as well as on the diagnostic concordance of biopsy and final surgery specimens. Two authors performed the literature search independently, while other two authors assessed the retrieved publications’ risk of bias using Begg’s and Egger’s tests. Twenty-four studies were included in the final report. Results: Both techniques have shown high effectiveness in diagnosing endometrial cancer, although with important differences. Hysteroscopy provides direct visualization of the endometrium and allows clinicians to perform biopsies of suspicious lesions, but it also entails important limitations, as in the case of diffused lesions or technical difficulties, especially in nulliparous and elderly women. VABRA and other vacuum biopsy techniques, on the other hand, offer a wider sampling of endometrial tissue and are less operator-dependent but may be associated with a higher risk of failed diagnosis when compared to hysteroscopy. Discussion: Hysteroscopy, especially when combined with targeted biopsies, has been proven to be a valid technique, especially in pre-surgical diagnostic workup of early-stage endometrial cancer. Vacuum techniques, although less invasive and providing larger tissue samples, do not seem to be able to completely replace hysteroscopy in diagnosing endometrial cancer but remain a valid alternative in selected cases, especially when endometrial lesions prove harder to reach and/or to identify. They may also prove useful in low resource countries in which hysteroscopy is not widely available. Conclusions: Based on our findings, early assessment of endometrial cancer should be carried out through hysteroscopic evaluation and targeted endometrial biopsies, ideally including molecular assessment on biopsy specimens to further guide treatment decisions. Other biopsy techniques, such as vacuum-assisted biopsy, should be reserved for specific settings in which hysteroscopy is not readily available. The ideal diagnostic approach to endometrial cancer should take multiple factors into account, such as the location and extension of the disease, patient characteristics, clinical skills, and resource availability. Further studies are needed to assess the feasibility of molecular cancer profiling on biopsy specimens, as well as cost-containment strategies which would allow equal access to targeted treatment modalities for all endometrial cancer patients worldwide. Full article

Background/Objectives: Endometrial cancer (EC) is a prevalent gynecological malignancy with an increasing incidence, particularly in developed countries. Recent research has demonstrated the significant involvement of gut and endometrial microbiomes in the pathogenesis and progression of EC. This review provides a comprehensive overview of the existing knowledge on the interactions between these microbial communities and their influence on EC. Methodology: A literature review was conducted using electronic databases including Google Scholar, Scopus, and PUBMED, covering the period from 2017 to 2024. The following keywords were used for the literature search: (1) gut microbiome and endometrial cancer, (2) endometrium microbiome and endometrial cancer, and (3) endometrial cancer and microbial dysbiosis. The selected articles were chosen based on inclusion and exclusion criteria. Scale for Assessment of Narrative Review Articles (SANRA) was used for evaluating and assessing the quality of articles. Results: The gut microbiome modulates systemic inflammation, immune responses, and estrogen metabolism, all of which are crucial factors in EC development. Dysbiosis is an imbalance in the composition of microbes that can cause chronic inflammation and hormonal imbalances, which can contribute to the EC. Similarly, the endometrial microbiome, while less extensively studied, has been implicated in EC through mechanisms involving local immune modulation and the production of harmful metabolites. Probiotics, prebiotics, fecal microbiota transplantation (FMT), and personalized microbiota-based therapies can be used as clinical interventions for EC management. This review emphasizes the need for further research to explore the gut–endometrium axis and its potential for innovative therapeutic approaches. Understanding these complex interactions will become a novel strategy to prevent and treat EC, ultimately enhancing patient outcomes. Full article

Endometrial cancer is the fourth most common cancer in women in Europe. Its carcinogenesis is a complex process and requires further research. In our study, we focus on finding new and easy-to-diagnose markers for detecting endometrial cancer. For this purpose, we compared the levels of miR-21-5p, miR-205-5p, and miR-222-3p in endometrial cancer tissues with the levels of these miRs in the serum of patients using the dPCR method. Our study is preliminary and consists of comparing the changes in miRNA expression in serum to the changes in miRNA in tissue of patients with endometrial cancer. The study included 18 patients with EC and 19 patients undergoing surgery for pelvic organ prolapse or uterine fibroids as a control group without neoplastic lesions. Endometrial tissue and serum were collected from all patients. The analyses showed an increased expression of miR-205-5p in endometrial cancer tissue and decreased expression of miR-222-3p in tissue and serum samples. These results suggest that miR-205-5p and miR-222-3p may be potential endometrial cancer biomarkers. Only miR-222-3p confirmed its decreased expression in serum, making it a potential and easily accessible marker in the diagnosis of endometrial cancer. This pilot study requires further investigation in a larger group of patients. Its advantages include the possibility of a comparison between miRNA expression in tissue and serum, as well as conducting the study using dPCR. Full article

Background and Clinical Significance: This study presents a case of a 43-year-old female with a long history of infertility, treated for uterine leiomyoma and endometrial hyperplasia, over a total observation period of 42 months. Case Presentation: Levonorgestrel intrauterine device (LNG-IUD) therapy, as a first and subsequent line of treatment, was introduced. The patient also received medroxyprogesterone acetate oral treatment. Finally, she underwent surgery for an ovarian tumor that appeared to be an ovarian adenocarcinoma concurrent with endometrial cancer. After the removal of the reproductive organ, the patient was diagnosed with synchronous low-grade endometrioid adenocarcinoma in the endometrium and a concurrent grade 2 (G2) endometrioid adenocarcinoma in the left ovary. Conclusions: The prognosis and further management largely depend on whether these are two individual neoplasms or one metastatic tumor. Considering the young age of the patients, an early disease stage, a low grade of both cancers, and favorable prognosis, most synchronous endometrial and ovarian cancers are identified as two independent primary tumors. The diagnosis of a multi-focal neoplasm is important, as in patients with endometrial cancer and ovarian metastasis, the 5-year survival rate is 30–40%, whereas in the case of individual neoplasms, it is 75–80%. Full article