Endometrial Cancer Research Articles

Role of HOXA10 in pathologies of the endometrium.

HOXA10 belongs to the homeobox gene family and is essential for uterine biogenesis, endometrial receptivity, embryo implantation, and stromal cell decidualization. Available evidence suggests that the expression of HOXA10 is dysregulated in different endometrial disorders like endometrial hyperplasia, endometrial cancer, adenomyosis, endometriosis, recurrent implantation failure, and unexplained infertility. The downregulation of HOXA10 occurs by genetic changes in the HOXA10 gene, methylation of the HOXA10 locus, or selected miRNAs. Endocrine disruptors and organic pollutants also cause the reduced expression of HOXA10 in these conditions. In vivo experiments in mouse models and in vitro studies in human cell lines demonstrate that downregulation of HOXA10 leads to endometrial epithelial cell proliferation, failure of stromal cell decidualization, altered expression of genes involved in cell cycle regulation, immunomodulation, and various signaling pathways. These disruptions are speculated to cause infertility associated with the disorders of the endometrium.

Germline copy number variants and endometrial cancer risk.

Known risk loci for endometrial cancer explain approximately one third of familial endometrial cancer. However, the association of germline copy number variants (CNVs) with endometrial cancer risk remains relatively unknown. We conducted a genome-wide analysis of rare CNVs overlapping gene regions in 4115 endometrial cancer cases and 17,818 controls to identify functionally relevant variants associated with disease. We identified a 1.22-fold greater number of CNVs in DNA samples from cases compared to DNA samples from controls (p = 4.4 × 10-63). Under three models of putative CNV impact (deletion, duplication, and loss of function), genome-wide association studies identified 141 candidate gene loci associated (p < 0.01) with endometrial cancer risk. Pathway analysis of the candidate loci revealed an enrichment of genes involved in the 16p11.2 proximal deletion syndrome, driven by a large recurrent deletion (chr16:29,595,483-30,159,693) identified in 0.15% of endometrial cancer cases and 0.02% of control participants. Together, these data provide evidence that rare copy number variants have a role in endometrial cancer susceptibility and that the proximal 16p11.2 BP4-BP5 region contains 25 candidate risk gene(s) that warrant further analysis to better understand their role in human disease.

The Accuracy of Arterial Phase of Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Predicting Cervical Stromal Invasion in Patients with Endometrial Carcinoma

Background: Endometrial cancer is the most common gynecological cancer. Cervical stromal invasion in patients with endometrial carcinoma is associated with local recurrence and overall survival, making accurate preoperative evaluation essential. Currently, the delayed phase of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is recommended for diagnosing cervical stromal invasion. However, this approach is time-consuming, and diagnostic interpretations can vary across observers and institutions. Objectives: To compare the diagnostic accuracy of arterial-phase and delayed-phase DCE-MRI for detecting cervical stromal invasion in endometrial carcinoma. Patients and Methods: This cross-sectional study retrospectively collected data from 445 patients with endometrial cancer. Two radiologists jointly evaluated cervical stromal invasion using histopathology as the gold standard reference. The McNemar test was used to compare the sensitivity and specificity of cervical stromal invasion detection between the arterial and delayed phases of DCE-MRI. Logistic regression analysis was conducted to assess the impact of tumor location and cervical lesions on diagnostic accuracy for cervical stromal invasion using DCE-MRI. Results: The mean age of the study population was 53.5 years [standard deviation (SD) = 3.1]. Dynamic contrast-enhanced magnetic resonance imaging images of the cervix demonstrated distinct enhancement characteristics. For detecting cervical stromal invasion, arterial-phase DCE-MRI showed a sensitivity of 66.4% [95% confidence interval (CI): 60.0 - 74.6%] and a specificity of 87.9% (95% CI: 83.9 - 91.0%). In the delayed phase, sensitivity was 69.1% (95% CI: 60.0 - 77.1%) and specificity was 88.2% (95% CI: 84.3 - 91.2%). There was no statistically significant difference between the arterial and delayed phases (P = 1.00). Factors influencing the assessment of cervical stromal invasion included the cluster distribution of Nabothian cysts and lesions located in the lower uterine segment or the internal os (P = 0.01, P &lt; 0.01). Conclusion: The arterial phase of DCE-MRI is a feasible, time-saving, and effective approach for detecting cervical stromal invasion in endometrial carcinoma.

Efficacy and safety of immune checkpoint inhibitors combined with chemotherapy or tyrosine kinase inhibitors in advanced endometrial cancer: A systematic review and meta-analysis.

The objective of this meta-analysis was to conduct a comprehensive assessment of the therapeutic effectiveness and safety profile of the combination of immune checkpoint inhibitors (ICIs) with either chemotherapy or tyrosine kinase inhibitors (TKIs) in the treatment of advanced-stage endometrial cancer (EC). This meta-analysis conducted a thorough literature search across PubMed, Cochrane Library, Embase, and Web of Science databases from their earliest records up to November 18th, 2023, identifying qualified randomized controlled trials (RCTs), cohort studies, and single-arm trials for inclusion in the analysis. The meta-analysis were performed to quantify and analyzed the evidence from the existing literature, focusing on outcomes including the objective response rate (ORR), disease control rate (DCR), duration of response (DOR), overall survival (OS), progression-free survival (PFS), and adverse events (AE). A total of 13 studies were included. In terms of ICI combined with chemotherapy, the single-arm trials showed that ICI combined with chemotherapy was effective in improving the ORR, but the overall rate of AE was higher. The results based on RCT suggested that ICI combined with chemotherapy resulted in a longer PFS of 12-24 months and OS of 18-month compared to the control group in advanced EC. In terms of ICI combined with TKI, the pooled ORR was 39.0%, the pooled DCR was 79.9%, the pooled OS rate was 50.4%, and the pooled overall AE rate was 95.8%, the pooled grade ≥3 AE rate was 73.8%, the pooled median progression-free survival (mPFS) was 6.126 months, and pooled OS was 15.099 months in advanced EC. The integrative therapeutic approach combining (ICIs) with chemotherapy or (TKIs demonstrates notable clinical efficacy in advanced EC, which can prolong the survival and help to disease control. Nevertheless, it is imperative for clinicians to be vigilant regarding the potential for adverse reactions to emerge. In addition, more RCTs are needed to solidify this study's efficacy and safety further.

Thyroid cancer in a child with Cowden syndrome

Cowden disease (Cowden syndrome) refers to PTEN-associated hamartoma tumor syndromes. It arises due to a mutation in the phosphatase and tensin homolog gene, one of the main functions of which is cell cycle regulation. The presence of a mutation in the gene leads to uncontrolled cell growth, and patients have a lifelong increased risk of neoplasms of various degrees of malignancy. This article presents a clinical case of Cowden syndrome with an early debut at the age of 7 years. The combination of macrocephaly (SDS of head circumference &gt;2) with various skin manifestations (facial trichilemmomas, acral keratosis, papillomatous papules) and the presence of benign and/or malignant neoplasms are pathognomonic for Cowden syndrome. Of the malignancies, breast and thyroid cancer, colorectal cancer, renal cell carcinoma, and endometrial cancer are the most common. Thyroid carcinoma has been shown to have an earlier age of manifestation and often occurs already in childhood. This determines the need to screen patients with a proven mutation in the PTEN gene for nodal neoplasms from an early age. If surgical treatment is necessary, thyroidectomy remains preferable due to the frequent recurrence of nodules, as well as the uncertain potential for malignancy due to the low study of thyroid nodules in patients with mutations in the PTEN gene.

Retracted] Stimulation of peroxisome proliferator‑activated receptor γ inhibits estrogen receptor α transcriptional activity in endometrial carcinoma cells.

Following the publication of this paper, after having performed an independent analysis of the data shown in the various of the figures in the Editorial Office, it was identified that, in Fig. 5A and B on p. 1232 showing the results of Transwell invasion and migration experiments, the majority of the data panels exhibited overlapping sections of data, such that the affected panels, which were intended to show the results of differently performed experiments, had all apparently been derived from the same original sources. Owing to the large number of duplications of data that have been identified in this paper, the Editor of Oncology Reports has decided that it should be retracted from the Journal on account of a lack of confidence in the presented data. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 33: 1227‑1234, 2015; DOI: 10.3892/or.2015.3729].

NEDD4 Knockdown Suppresses Human Endometrial Stromal Cell Growth and Invasion by Regulating PTGS2-Mediated Ferroptosis in Endometriosis.

Endometriosis (EM) is a gynecological disease characterized by the benign growth of endometrial tissue outside the uterus. Upregulation of neuronally expressed developmentally downregulated 4 (NEDD4) has been reported to accelerate endometrial cancer progression. We explored whether abnormal expression of NEDD4 is correlated with EM. Endometrial tissue in patients without endometriosis was used to develop the original generation of endometrial stromal cells (ESCs). Different types of endometrial tissue of patients with endometriosis were used to measure the expression of NEDD4 by immunohistochemistry (IHC) and western blotting. Its biological functions in ESCs were investigated using a cell counting kit-8 assay, fluorescein diacetate (FDA) staining, and Transwell invasion assays. Additionally, its involvement in ferroptosis was assessed by measuring Fe2+, malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) levels and the expression of ferroptosis markers. Compared with normal controls, NEDD4 levels were significantly elevated in the endometrial tissue of patients with EM. Furthermore, NEDD4 expression was higher in the ectopic endometrium than in the eutopic endometrium. NEDD4 knockdown reduced the viability and invasive capacity of ESCs, increased Fe2+, MDA, and ROS levels, and decreased GSH content. Further analysis revealed that NEDD4 knockdown promoted ferroptosis in ESCs by increasing the expression of prostaglandin-endoperoxide synthase 2 (PTGS2). As an E3 ubiquitin ligase, NEDD4 reduced PTGS2 protein levels by accelerating its ubiquitination and subsequent proteasomal degradation. These findings suggest that inhibiting NEDD4 reduces ESC growth and invasion in EM by regulating PTGS2-dependent ferroptosis.

The causal relationship between anti-CD20 antibodies and endometrial cancer: a Mendelian randomization study

PurposeTo determine the effects of anti-B cell surface marker CD20 antibody on the occurrence and progression of endometrial cancer to provide insights into clinical treatment in the future.MethodsWe performed a two-sample Mendelian randomization analysis (MR) to analyze the causal relationship between EC and immune cell markers. The genome-wide association study (GWAS) data of MS4A1 single nucleotide polymorphism encoding gene of CD20 were collected, and a drug target MR analysis was performed to detect the causal relationship between anti-CD20 antibody and the risk of EC. The risk of follicular lymphoma was used as a positive control, and EC was used as the outcome.ResultsEC exerted an effect on 28 immunophenotypes, predominantly on CD20. CD20 in immunoglobulin D+ CD38− B cells, memory B cells, and unsw memory B cells increased after EC onset. In addition, we detected one immunophenotype that exerted a dangerous effect on EC, i.e., CD3/TD CD4+ (mature stage of the T cell group). Simultaneously, CD20 could be used as both a risk factor and a protective factor for EC (P > 0.05). Anti-CD20 antibodies significantly reduced the risk of follicular lymphoma, including two GWAS pooled datasets. In addition, anti-CD20 antibodies exerted a protective effect on EC in two GWAS pooled datasets (P > 0.05).ConclusionOur study confirms the close relationship between CD20 and EC. Anti-CD20 antibodies may exert a protective effect on EC and reduce the risk of EC morbidity, providing a reference for future clinical diagnosis and treatment. However, further clinical verification of our results is warranted.

Association between cholelithiasis, cholecystectomy, and risk of breast and gynecological cancers: Evidence from meta-analysis and Mendelian randomization study.

Observational studies have shown that cholelithiasis and cholecystectomy are associated with the risk of breast cancer (BC) and gynecological cancers, but whether these relationships are causal has not been established and remains controversial. Our study began with a meta-analysis that synthesized data from prior observational studies to examine the association between cholelithiasis, cholecystectomy, and the risk of BC and gynecological cancers. Subsequently, a two-sample Mendelian randomization (MR) analysis was conducted utilizing genetic variant data to investigate the potential causal relationship between cholelithiasis, cholecystectomy, and the aforementioned cancers. The results of the meta-analysis demonstrated a significant association between cholecystectomy and the risk of BC (risk ratio [RR]=1.04, 95% confidence interval [CI]: 1.01-1.06, p=0.002) and endometrial cancer (EC) (RR=1.26, 95% CI: 1.02-1.56, p=0.031). Conversely, no significant association was observed between cholelithiasis and the risk of BC, EC, and ovarian cancer. The MR analysis revealed no discernible causal connection between cholelithiasis and overall BC (p=0.053), as well as BC subtypes (including estrogen receptor-positive/negative). Similarly, there was no causal effect of cholecystectomy on BC risk (p=0.399) and its subtypes. Furthermore, no causal associations were identified between cholelithiasis, cholecystectomy, and the risk of gynecological cancers (ovarian, endometrial, and cervical cancer [CC]) (all p>0.05). This study does not support a causal link between cholelithiasis and cholecystectomy and an increased risk of female cancers such as breast, endometrial, ovarian, and CC.

A Multicenter Cohort Study on DNA Methylation for Endometrial Cancer Detection in Cervical Scrapings.

The increasing incidence of endometrial cancer (EC) has highlighted the need for improved early detection methods. This study aimed to develop and validate a novel DNA methylation classifier, EMPap, for EC detection using cervical scrapings. EMPap incorporated the methylation status of BHLHE22 and CDO1, along with age and body mass index (BMI), into a logistic regression model to calculate the endometrial cancer methylation (EM) score for identifying EC in cervical scrapings. We enrolled 1297 patients with highly suspected EC, including 196 confirmed EC cases, and assessed the EMPap performance in detecting EC. EMPap demonstrated robust diagnostic accuracy, with an area under the curve of 0.93, sensitivity of 90.3%, and specificity of 89.3%. It effectively detected EC across various disease stages, grades, and histological subtypes, and consistently performed well across patient demographics and symptoms. EMPap correctly identified 87.5% of the type II ECs and 53.8% of premalignant lesions. Notably, compared with transvaginal ultrasonography (TVS) in patients with postmenopausal bleeding, EMPap exhibited superior sensitivity (100% vs. 82.0%) and specificity (85.2% vs. 38.5%). In asymptomatic postmenopausal women, EMPap maintained high sensitivity (89.5%) and negative predictive value (NPV) (98.3%). This study demonstrated the potential of EMPap as an effective tool for EC detection. Despite the limited sample size, EMPap showed promise for identifying type II EC and detecting over 50% of premalignant lesions. As a DNA methylation classifier, EMPap can reduce unnecessary uterine interventions and improve diagnosis and outcomes.

Causal effect of breast cancer on endometrial cancer risk: A two-sample Mendelian randomization study

BackgroundObservational studies have indicated a higher incidence of endometrial cancer in individuals with breast cancer. However, to date, there is a dearth of Mendelian randomization studies that explore the causal relationship between breast cancer and the risk of endometrial cancer. Material and methodsWe conducted Mendelian randomization (MR) to investigate the causal relationship between breast cancer and endometrial cancer risk in European populations. ResultsA total of 112 valid instrumental variables were included in the analysis. Our research has revealed a compelling causal association between genetic predisposition for breast cancer and an augmented likelihood of developing endometrial cancer (Inverse variance weighted (IVW) method, odds ratio (OR) = 1.105, 95 % confidence interval (CI): 1.025 to 1.181, p = 0.003; Weighted median method, OR = 1.109, 95 % CI: 1.020 to 1.205, p = 0.015; Weighted mode method: OR = 1.101, 95 % CI: 1.013 to 1.195, p = 0.025). ConclusionTo our knowledge, this study is the first to report a causal association between breast cancer and endometrial cancer risk. Robust results were obtained through rigorous testing for heterogeneity and pleiotropy. Our findings indicate a causal effect of breast cancer on the risk of endometrial cancer.

Diagnostic value of transvaginal contrast-enhanced ultrasound in identifying benign and malignant endometrial lesions and assessing myometrial invasion.

The objective of this study was to evaluate the diagnostic value of transvaginal contrastenhanced ultrasound (CEUS) in differentiating benign from malignant endometrial lesions and assessing the extent of myometrial invasion. A total of 70 patients who underwent surgery for endometrial lesions at the authors' hospital were selected. Transvaginal ultrasound examination and CEUS were performed for quantitative and qualitative analysis. Based on the CEUS results, an International Federation of Gynecology and Obstetrics (FIGO) disease grade was assigned and compared with pathological findings. Postmenopausal vaginal bleeding is a key clinical manifestation of endometrial carcinoma. Among the patients with endometrial carcinoma, compared with normal myometrium, the lesion areas exhibited a greater rate of rise (defined as enhanced intensity divided by enhancement time) and a shorter half-clearance time (P<0.05). These findings suggest that in endometrial carcinoma, the contrast agent displays a "fast-in/fast-out/hyperenhancement" perfusion pattern. In contrast, the characteristic perfusion pattern for benign endometrial lesions is low enhancement (P<0.05). The diagnostic accuracy of CEUS in detecting myometrial invasion was 88% (22 of 25 cases). Transvaginal CEUS is a practical and effective diagnostic imaging method for distinguishing between benign and malignant endometrial lesions. It can also be used to evaluate the depth of myometrial invasion in patients with early-stage endometrial carcinoma.

Evolution of endometrial cancer incidence patterns in Hong Kong: A three-decade analysis with future projections

ObjectiveThis study provides a comprehensive analysis of endometrial cancer incidence trends in Hong Kong over the past three decades. It aims to evaluate the impact of demographic shifts and epidemiological factors, including age, birth cohort, and diagnosis period, on the incidence rates. The study also projects future trends in endometrial cancer cases up to 2030 and assesses the contributions of these factors using a detailed decomposition approach. Material and methodsThe analysis is based on endometrial cancer data obtained from the Hong Kong Cancer Registry. Age-period-cohort (APC) modeling was utilized to investigate the effects of different age groups, historical periods, and birth cohorts on the changing incidence patterns. The study projects future trends using a Bayesian APC framework, integrating historical data and expert insights for robust predictions. Additionally, a decomposition analysis was conducted to disentangle the contributions of demographic changes (aging and population growth) and epidemiological shifts (risk factors such as obesity and reproductive behaviors) to the increasing cases. ResultsBetween 1992 and 2021, there were 19,214 recorded cases of endometrial cancer in Hong Kong. Age-standardized and crude incidence rates showed consistent increases, rising from 7.4 per 100,000 person-years in 1992 to 31.0 per 100,000 in 2020. Incidence trends rose significantly across all age groups, with the highest increase seen in women aged 50–65. Projections indicate that the upward trend will continue, with an estimated 1718 cases by 2030. Demographic factors, particularly population aging, and evolving epidemiological trends contribute jointly to the incidence rise. ConclusionsThe findings reveal a steady increase in endometrial cancer incidence among Hong Kong women, primarily driven by demographic aging and shifts in risk factors. The study underscores the need for targeted public health measures and resource allocation for early detection and effective management strategies, emphasizing the importance of addressing modifiable risk factors such as obesity and reproductive health behaviors.

First-degree family history of cancer in women with stage I endometrial carcinoma: Prevalence and prognostic impact

First-degree family history of cancer in women with stage I endometrial carcinoma: Prevalence and prognostic impact

Excellent concordance of the molecular classification between preoperative biopsy and final hysterectomy in endometrial carcinoma

ObjectiveThe 2023 International Federation of Gynecology and Obstetrics classification with molecular classification shows superior discriminatory ability compared to staging systems lacking molecular data. However, the accuracy of endometrial biopsy data in molecular classification remains uncertain. This study aimed to assess the concordance of molecular classifications between preoperative biopsy and hysterectomy to predict prognosis before surgical staging. MethodsEndometrial biopsies and corresponding hysterectomy specimens were collected at the National Cancer Center Hospital between 2012 and 2023. Immunohistochemistry for p53 and mismatch repair (MMR) proteins and next-generation sequencing of all exons of polymerase epsilon (POLE) were performed. Given the limited number of POLE mut cases in prior studies, we prepared a POLE mut-enriched cohort. Cohen's kappa estimates were used to determine concordance for molecular and clinicopathological subgroup assignments. ResultsAmong 70 patients classified into four molecular subtype groups, 33 exhibited POLE mutations, 15 showed loss of MMR protein expression, 13 had p53-abnormality, and 9 had no specific molecular profile. Concordance between biopsy and hysterectomy specimens was 100% (κ = 1.000). In contrast, histological types and grades between biopsy and surgical specimens showed moderate and substantial agreement (κ = 0.420 and κ = 0.780, respectively). ConclusionsMolecular subtypes were completely consistent with those derived from surgical specimens, demonstrating high concordance between preoperative and postoperative molecular classifications. This suggests that endometrial biopsies could reliably predict prognosis. Future studies should investigate how biopsy-based molecular profiling influences treatment planning and patient outcomes.

Frequency and outcomes of co-mutations according to ProMisE classifiers in endometrial cancer

Frequency and outcomes of co-mutations according to ProMisE classifiers in endometrial cancer

Is presumed clinical stage I endometrial cancer in PET/CT and MRI truly stage I in surgical staging?

Is presumed clinical stage I endometrial cancer in PET/CT and MRI truly stage I in surgical staging?

Healthcare delivery in patients with endometrial cancer in Colombia: A national cohort study based on administrative claims data

Healthcare delivery in patients with endometrial cancer in Colombia: A national cohort study based on administrative claims data

Concurrent POLE hotspot mutations and mismatch repair deficiency in endometrial cancer: Defining cancer drivers

Concurrent POLE hotspot mutations and mismatch repair deficiency in endometrial cancer: Defining cancer drivers

Aberrant expression of progesterone receptor isoforms in endometrial hyperplasia and endometrial cancer

Aberrant expression of progesterone receptor isoforms in endometrial hyperplasia and endometrial cancer