Analysis of ultrasonic imaging changes and factors related to malignant transformation in postmenopausal patients with endometrial polyps.

OBJECTIVE: To examine the ultrasonic changes in postmenopausal endometrial polyps and analyze factors related to their malignant transformation. METHODS: This retrospective study analyzed clinical data from 200 postmenopausal patients with endometrial polyps treated at Jinan Maternity and Child Care Hospital and Pingyin Hospital of Traditional Chinese Medicine from December 2020 to December 2023. All patients underwent pathological biopsies to diagnose the nature of the endometrial polyps. This study compared the clinical and ultrasonic imaging features of these patients and analyzed factors influencing the malignant transformation of postmenopausal endometrial polyps. RESULTS: Pathological findings classified 160 patients (80.00%) into the benign group and 40 patients (20.00%) into the malignant group. Significant differences were noted in endometrial thickness, polyp diameter, heterogeneity of lesion echogenicity, and vascularization between the groups (all P<0.05). The malignant group exhibited notably higher blood flow (Grade II+III constituted 70.00% compared to 29.38% in the benign group, P<0.05). The time average velocity (TAV), pulse index (PI), and resistance index (RI) were significantly lower in the malignant group (all P<0.05). The area under curve (AUC) values for TAV, PI, and RI in diagnosing malignant endometrial polyps were 0.754, 0.713, and 0.771, respectively. Increased body mass index (BMI), irregular premenopausal menstruation, and ≥2 occurrences of postmenopausal bleeding were identified as risk factors for malignant transformation (all P<0.05). These six indicators were used to create a predictive model for malignant transformation, achieving an AUC of 0.942. CONCLUSION: Malignancy in postmenopausal endometrial polyps is uncommon, yet distinct differences exist in the transvaginal color Doppler ultrasound characteristics between benign and malignant cases. Factors such as increased BMI, irregular premenopausal menstruation, and ≥2 occurrences of postmenopausal bleeding significantly contribute to the risk of malignant transformation. These findings, combined with ultrasound features, provide a robust basis for screening and monitoring these patients.

Endometrial Clear Cell Carcinoma with Non-Gestational Uterine Choriocarcinoma Differentiation.

Choriocarcinoma is a rare and highly malignant tumor that primarily occurs in women of reproductive age. Choriocarcinoma can be classified as gestational or nongestational, based on its pathogenetic origin. Although primary nongestational choriocarcinoma has been described in the ovaries, it is very rare in the uterus, especially in postmenopausal women. It is crucial to differentiate between gestational and non-gestational choriocarcinoma, as it affects the choice of treatment and prognosis. Endometrial clear cell carcinoma is an aggressive subtype of endometrial cancer, accounting for less than 10% of all uterine carcinomas. Trophoblastic differentiation in uterine cancer is unusual and very rare, with only three examples of the subtype of clear cell endometrial cancer with gestational choriocarcinoma reported in the literature, including only one with nongestational choriocarcinoma. Here, we present an example of clear cell carcinoma with nongestational uterine choriocarcinoma differentiation in a postmenopausal woman.

Identification of a disulfidptosis-related prognostic signature for prediction of the effect of treatment in patients with endometrial carcinoma.

Background: Disulfide, an essential compounds family, has diverse biological activity and can affect the dynamic balance between physiological and pathological states. A recently published study found that aberrant accumulation of disulfide had a lethal effect on cells. This mechanism of cell death, named disulfidptosis, differs from other known cell death mechanisms, including cuproptosis, apoptosis, necroptosis, and pyroptosis. The relationship between disulfidptosis and development of cancer, in particular endometrial carcinoma, remains unclear. Methods: To address this knowledge gap, we performed a preliminary analysis of samples from The Cancer Genome Atlas database. The samples were divided equally into a training group and a test group. A total of 2308 differentially expressed genes were extracted, and 11 were used to construct a prognostic model. Results: Based on the risk score calculated using the prognostic model, the samples were divided into a high-risk group and a low-risk group. Survival time, tumor mutation burden, and microsatellite instability scores differed significantly between the two groups. Furthermore, a between-group difference in treatment effect was predicted. Comparison with other models in the literature indicated that this prognostic model had better predictive anility. Conclusion: The results of this study provide a general framework for understanding the relationship between disulfidptosis and endometrial cancer that could be used for clinical evaluation and selection of appropriate personalized treatment strategies.

KIF2A correlates with lymphovascular invasion and higher tumor stage, and can be used to predict worse prognosis in patients with endometrial carcinoma.

Kinesin family protein 2A (KIF2A) is a microtubule depolymerase that participates in the progression of various cancers; however, its clinical utility in endometrial carcinoma (EC) remains unclear. The aim of the present study was to assess KIF2A expression and its relationship with prognosis in patients with EC. Data from 230 patients with EC who underwent tumor resection were reviewed in the current, retrospective study. KIF2A expression was measured in 230 formalin-fixed paraffin-embedded (FFPE) specimens of tumor tissue and 50 FFPE specimens of non-tumor tissue using immunohistochemistry (IHC). KIF2A expression was elevated in EC tumor tissue vs. non-tumor tissue (P<0.001). Furthermore, tumor KIF2A expression was linked with lymphovascular invasion (P=0.004) and higher International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.001). High tumor KIF2A expression (IHC score>3) was correlated with shorter disease-free survival (DFS; P=0.014) and overall survival (OS; P=0.012). Moreover, the time-dependent receiver operating characteristic curves revealed that tumor KIF2A expression had an acceptable use for estimating the relapse and death risks at each timepoint within 6 years, with each area under the curve remaining stable at ≥0.7. Notably, tumor KIF2A expression (high vs. low) independently forecast shorter DFS (hazard ratio, 2.506; P=0.013), but not OS (P>0.05). Furthermore, information from The Human Protein Atlas database indicated that high tumor KIF2A expression was associated with worse OS in patients with EC (P=0.027). Tumor KIF2A is not only associated with lymphovascular invasion and higher FIGO stage, but also reflects unfavorable survival in patients with EC.

Metastatic endometrial carcinoma presenting as a scapular mass: A case report and literature review.

Bone metastases of endometrial cancers are quite rare, especially in the scapula. Only two previous reports of such cases were found in the literature, and in each case a different approach to diagnosis was used. There are no established recommendations for screening for bone metastases at diagnosis or after initial treatment of endometrial cancers. In the present case, a 55-year-old woman with progressive abdominal distension was diagnosed with a cystic mass. Histopathological analysis revealed grade II synchronous endometrioid carcinoma in both the endometrium and the ovaries. The patient received three cycles of combined paclitaxel and carboplatin chemotherapy. Seven months after the last chemotherapy cycle, a palpable lump was found in the right shoulder, suggesting a lesion in the right scapula. A bone scan revealed heightened radioactivity uptake, highlighting the unpredictable nature of the disease progression. The choice of diagnostic imaging modality remains challenging. This case emphasises the need for ongoing investigation of the mechanisms of distant metastasis and for the development of standardised diagnostic and therapeutic strategies.

The impact of estrogen receptor and L1 cell adhesion molecule expression on endometrial cancer outcome correlates with clinicopathological risk group and molecular subgroup.

OBJECTIVE: To assess the risk stratification of clinicopathologically and molecularly classified endometrial cancer based on estrogen receptor (ER) and L1 cell adhesion molecule (L1CAM) expression. METHODS: This was a retrospective study of patients who underwent primary treatment at a single tertiary center. Carcinomas were classified into 5 clinicopathological risk groups, as per European guidelines. Immunohistochemistry and polymerase-ϵ sequencing were conducted for molecular classification and determination of ER and L1CAM expression. RESULTS: Data from 1044 patients were analyzed. The median follow-up was 67.5 months. In univariable analyses, ER expression correlated with improved disease-specific survival (DSS) in the "no specific molecular profile" (NSMP) (P < 0.001) and mismatch repair deficient (MMRd) (P = 0.002) subgroups. Negative L1CAM expression was associated with enhanced DSS in the NSMP subgroup alone (P < 0.001). ER (hazard ratio [HR] 0.18), but not L1CAM, exhibited prognostic significance within NSMP when controlling for parameters available at the time of diagnosis (tumor histotype, grade, age). ER and L1CAM were not independently associated with DSS within NSMP when controlling for parameters available after surgery (clinicopathological risk groups, age, adjuvant therapy). However, in high-risk-advanced-metastatic cases, both ER (HR 0.26) and L1CAM (HR 3.9) independently correlated with DSS. Similarly, within MMRd, ER was associated with improved DSS in high-risk-advanced-metastatic carcinomas (HR 0.42). CONCLUSION: The prognostic significance of ER and L1CAM varies across clinicopathological risk groups and molecular subgroups of endometrial cancer. Notably, risk assessment for high-risk-advanced-metastatic NSMP and MMRd subtype carcinomas can be refined by ER status.

Endometrial serous carcinoma with a corded and hyalinized pattern: a clinicopathological and molecular analysis.

A corded and hyalinized pattern has been described in endometrial endometrioid carcinoma. Herein, we describe a clinicopathological and molecular analysis of the first reported case of endometrial serous carcinoma with a corded and hyalinized pattern.A 64-year-old woman underwent hysterectomy and bilateral salpingo-oophorectomy due to a 5.5 cm endometrial lesion. Histologically, the tumor was composed of a minor (20%) serous carcinoma component and a predominant corded component embedded in a hyaline-to-myxoid matrix. This component showed diffuse and strong p53 and p16 expression, heterogeneous positivity for epithelial markers and WT1, focal positivity for estrogen and progesterone receptors, retained MMR, SMARCA4/BRG1, and SMARCB1/INI1 expression, and negativity for smooth muscle, germ cell, sex cord, neuroendocrine, endothelial, and melanocytic markers and GATA3. Next-generation sequencing showed a mutation of uncertain significance in APC and no mutations in MLH1, MSH2, MSH6, PMS2, MUTYH, POLE, POLD1, EPCAM, or CTNNB1. The patient had a recurrence on the vaginal stump after 15 months.In conclusion, endometrial serous carcinoma can show a corded and hyalinized pattern, which may represent a diagnostic challenge.

Comparative effects of different treatments based on the levonorgestrel intrauterine system in endometrial carcinoma and endometrial hyperplasia patients: a network meta-analysis.

OBJECTIVE: Levonorgestrel intrauterine system (LNG-IUS) has been widely used in patients with endometrial carcinoma (EC), endometrial hyperplasia without atypical (EH), and atypical endometrial hyperplasia (AEH). The purpose of our Network meta-analysis (NMA) is to evaluate the efficacy of the treatments based on the LNG-IUS in patients with EC and EH with or without atypical. METHODS: We examined PubMed, EMBASE, Web of Science and the Cochrane Library up to 22 April 2024 to determine studies reporting treatment outcomes in EC and EH patients receiving LNG-IUS therapy, LNG-IUS + metformin (MET), oral progestins (OP), etc. We used EndNote 9 to select studies, Jadad scale and NOS scale to assess quality, stata(16.0) and R (4.3.1) to analysis the data. RESULTS: Overall, 28 studies involving 3752 patients were included in our NMA. As for EH patients, LNG-IUS (RR 1.21; 95% CrI [1.11, 1.34]) and LNG-IUS + MET (RR 323.57; 95% CrI [1.61, 214,223,188.1])] significantly increased CR rate in comparison with OP. Based on SUCRA, LNG-IUS + OP was the best treatment to improve CR(SUCRA = 67.2%) in patients with EC, whereas LNG-IUS + MET was superior in increasing CR (SUCRA = 99.8%) than any other treatments for EH patients. Besides, the ranking based on SUCRA illustrated that LNG-IUS alone was the best choice to raise CR rates (SUCRA = 76.7%) for AEH patients. In head-to-head meta-analysis, OP has a higher progression rate (RR 4, 95% CI 1.89-8.46, p = 0.062; I2 = 71.3%), a higher nausea rate (RR 1.93, 95% CI 1.24-3.01, p = 0.187; I2 = 40.4%) than LNG-IUS in patients with EH. In contrast, LNG-IUS had a irregular vaginal bleeding rates (RR 0.76, 95% CI 0.64-0.90, p = 0.034; I2 = 77.7%) than OP in EH patients. In addition, as for AEH patients, OP has a higher persistence rate (RR 4.31, 95% CI 1.43-13.00, p = 0.93; I2 = 0.0%) than LNG-IUS. CONCLUSION: According to the NMA, LNG-IUS related studies are feasible for conservative therapy in patients with EC and EH with or without atypical. Therefore, concerning the curative effect, we recommend LNG-IUS-based treatments as the best conservative therapy for EC and EH patients. However, future studies require large sample sizes and more outcomes to further evaluate the differences of treatment selections based on LNG-IUS.

Multiparameter MRI-based radiomics analysis for preoperative prediction of type II endometrial cancer.

Objectives: This study aimed to develop and validate a radiomics nomogram based on multiparameter MRI for preoperative differentiation of type II and type I endometrial carcinoma (EC). Methods: A total of 403 EC patients from two centers were retrospectively recruited (training cohort, 70 %; validation cohort, 30 %). Radiomics features were extracted from T2-weighted imaging, dynamic contrast-enhanced T1-weighted imaging at delayed phase(DCE4), and apparent diffusion coefficient (ADC) maps. Following dimensionality reduction, radiomics models were developed by logistic regression (LR), random forest (RF), bootstrap aggregating (Bagging), support vector machine (SVM), artificial neural network (ANN), and naive bayes (NB) algorithms. The diagnostic performance of each radiomics model was evaluated using the ROC curve. A nomogram was constructed by incorporating the optimal radiomics signatures with significant clinical-radiological features and immunohistochemistry (IHC) markers obtained from preoperative curettage specimens. The diagnostic performance and clinical value of the nomogram were evaluated using ROC curves, calibration curves, and decision curve analysis (DCA). Results: Among the radiomics models, the NB model, developed from 12 radiomics features derived from ADC and DCE4 sequences, exhibited strong performance in both training and validation sets, with the AUC values of 0.927 and 0.869, respectively. The nomogram, incorporating the radiomics model with significant clinical-radiological features and IHC markers, demonstrated superior performance in both the training (AUC = 0.951) and the validation sets (AUC = 0.915). Additionally, it exhibited excellent calibration and clinical utility. Conclusions: The radiomics nomogram has great potential to differentiate type II from type I EC, which may be an effective tool to guide clinical decision-making for EC patients.

Blood Vessel Invasion Is an Independent Prognostic Factor in Endometrial Endometrioid Carcinoma Compared to Lymph Vessel Invasion and Myometrial Invasion Pattern.

We studied 115 cases of EEC diagnosed on hysterectomy specimens. Double immunohistochemical staining (D2-40/CD31) was performed in all 115 cases to show LVI and BVI on the same slide. MELF pattern invasion was present in 24/115 (21%) cases. MELF-positive tumors had a higher frequency of LVI than MELF-negative tumors (58% and 23%, respectively); the frequency of BVI was twice as high in MELF-positive tumors in comparison to MELF-negative tumors (25% and 12%, respectively). These differences were significant (p ˂ 0.0001). All tumors with positive BVI also had a concomitant LVI. The presence of MELF invasion had no impact on overall survival, confirming previous studies. 5-year survival rates were almost equal in cases with negative LVSI and cases with positive isolated LVI (98% vs. 97%). However, in cases where BVI was also present, the 5-year survival rate was significantly lower, 63% (p ˂ 0.0001). Furthermore, BVI proved to be an independent prognostic factor for overall survival, disease-free survival, and recurrence in the multivariate analysis. In conclusion, MELF pattern invasion is a good predictor of lymphatic and blood vessel invasion but has no prognostic value. Our results suggest that BVI in EEC has greater clinical value than isolated LVI or myometrial invasion patterns, and the therapeutic approach should be guided by BVI presence. Therefore, we hope this study will promote the routine evaluation of BVI in the context of EEC diagnostic procedures.

Risk of endometrial malignancy in women treated for breast cancer: the BLUSH prediction model - evidence from a comprehensive multicentric retrospective cohort study.

OBJECTIVE: This study aimed to evaluate characteristics of endometrial surveillance in women treated for breast cancer to build a clinical prediction model. DESIGN: A multicentric retrospective cohort study was conducted at two tertiary-care university hospitals from January 2020 to June 2023. Perimenopausal and postmenopausal women treated for breast cancer were categorized into two groups: patients with and without diagnosis of endometrial malignancy (endometrial carcinoma) or premalignancy (atypical endometrial hyperplasia). Characteristics of breast cancer and ultrasonographic and hysteroscopic examinations were compared. A prediction model for endometrial malignancy was built using logistic regression. Predictive accuracy was assessed using the receiver operating characteristic (ROC) curve and goodness of fit using the Hosmer-Lemeshow test. RESULTS: One hundred and thirty-two (28 with premalignancy or malignancy and 104 without malignancy) women were analyzed. A nomogram was produced for prediction model development utilizing the presence and duration in months of abnormal uterine (BL)eeding, ultrasound (US) vascular pattern and echogenicity and (H)ysteroscopic appearance of endometrium (BLUSH) as determined by logistic regression. Sensitivity and specificity were 79.17% and 95.19%, respectively, with an area under ROC curve of 0.965, indicating good accuracy. Good goodness of fit and prediction stability were indicated by the calibration curve and Hosmer-Lemeshow test (χ2 = 26.36; p = 0.999). CONCLUSIONS: Breast cancer survivors undergoing endometrial surveillance might benefit from a potentially useful prediction model based on hysteroscopic appearance, ultrasonographic uniformity of endometrium, Doppler flow and presence of abnormal uterine bleeding.

LncRNA TRPM2-AS promotes endometrial carcinoma progression and angiogenesis via targeting miR-497-5p/SPP1 axis.

BACKGROUND: Anti-angiogenic therapy has become one of the effective treatment methods for tumors. Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and angiogenesis in EC. However, the underlying mechanisms of lncRNA TRPM2-AS in EC are still not clear. METHODS: We screened the differently expressed lncRNAs that were highly associated with poor prognosis and angiogenesis of EC by bioinformatics analysis, and constructed a ceRNA network based on the prognostic lncRNAs. The subcellular localization of TRPM2-AS was determined by fluorescence in situ hybridization (FISH) and nuclear cytoplasmic fractionation assay. CCK-8, EdU, transwell, western blot, qRT-PCR and endothelial tube formation assay were used to evaluate the effects of TRPM2-AS on the proliferation, invasion, migration of EC cells and angiogenesis. The targeted microRNA (miRNA) of TRPM2-AS was predicted by bioinformatic methods. The interaction between TRPM2-AS and miR497-5p, miR497-5p and SPP1 were analyzed by RNA immunoprecipitation and dual-luciferase reporter assay. A subcutaneous tumor model was used to explore TRPM2-AS's function in vivo. CIBERSORT was used to analyze the correlation between TRPM2-AS and immune cell immersion in EC. RESULTS: We found that the expression of TRPM2-AS and SPP1 was aberrantly upregulated, while miR-497-5p expression was significantly downregulated in EC tissues and cells. TRPM2-AS was closely correlated with the angiogenesis and poor prognosis in EC patients. Mechanistically, TRPM2-AS could sponge miR-497-5p to release SPP1, thus promoting the proliferation, invasion and migration of EC cells and angiogenesis of HUVECs. Knockdown of TRPM2-AS in xenograft mouse model inhibited tumor proliferation and angiogenesis in vivo. In addition, TRPM2-AS plays a vital role in regulating the tumor immune microenvironment of EC, overexpression of TRPM2-AS in EC cells stimulated the polarization of M2 macrophages and angiogenesis through secreting SPP1 enriched exosomes. CONCLUSION: The depletion of TRPM2-AS inhibits the oncogenicity of EC by targeting the miR-497-5p/SPP1 axis. This study offers a better understanding of TRPM2-AS's role in regulating angiogenesis and provides a novel target for EC treatment.

Corded and Hyalinized Endometrioid Endometrial Carcinoma: A Rare Case Treated With Robot-Assisted Surgery.

Endometrial carcinoma is the sixth most common cancer among women worldwide. Minimally invasive surgery (MIS) has become the preferred treatment, offering similar survival outcomes to laparotomy with lower complication rates. Corded and hyalinized endometrioid carcinoma (CHEC) is a rare and diagnostically challenging variant of endometrioid carcinoma, first described in 2005, characterized by a biphasic appearance of traditional low-grade endometrioid adenocarcinoma and corded and spindled cells embedded in a hyaline stroma. A 55-year-old nulligravid woman presented with abnormal genital bleeding for 10 days. Initial evaluations, including transvaginal ultrasonography and histological examination, confirmed adenocarcinoma. Imaging studies (magnetic resonance imaging [MRI] and computed tomography [CT]) revealed a thickened endometrium (11 mm) with no myometrial invasion, enlarged pelvic lymph nodes, or distant metastasis. Tumor markers were within normal ranges. She underwent robot-assisted laparoscopic total hysterectomy, bilateral adnexectomy, and pelvic lymph node biopsy using the da Vinci Xi system (Intuitive Surgical, Sunnyvale, CA). Histopathological examination revealed CHEC, with characteristic epithelioid and spindled cells arranged in cords within a hyalinized stroma. Immunohistochemical staining showed focal positivity for cytokeratin AE1/AE3, weak estrogen receptor positivity, and nuclear ß-catenin expression, distinguishing it from carcinosarcoma. The diagnosis was confirmed as CHEC, FIGO 2008 stage IA (pT1aN0M0). The patient remained disease-free 18 months post-surgery. CHEC is a rare variant of endometrioid carcinoma with unique histological features. It typically presents in younger patients at an early stage and has a favorable prognosis. Accurate diagnosis is crucial to differentiate it from more aggressive tumors like carcinosarcoma, preventing overtreatment. The immunohistochemical profile, particularly nuclear ß-catenin accumulation, is useful in distinguishing CHEC from carcinosarcoma. This is the first documented case of CHEC successfully treated with robot-assisted surgery. Increased awareness among pathologists and clinicians is essential for accurate diagnosis and optimal management of this rare tumor variant.

Universal screening for Lynch syndrome in endometrial cancer diagnoses in Auckland, New Zealand: The initial experience.

BACKGROUND: Universal mismatch repair immunohistochemistry (MMR IHC) tumour testing in endometrial cancer (EC) for Lynch syndrome (LS) was introduced in Auckland, New Zealand, in January 2017. Identifying patients with LS allows them and their families to access risk reduction strategies. Universal MMR IHC testing aids in the molecular classification of EC and has prognostic and therapeutic implications. AIM: We aimed to determine the incidence of LS in women with EC in Auckland, New Zealand, following the introduction of MMR testing and the impact of universal screening on local genetic services. MATERIALS AND METHODS: This is a retrospective clinicopathological evaluation of women with a new EC diagnosis referred to the Auckland Gynaecological Oncology Unit from 1/1/17 to 31/12/18. Patient data were extracted from the Gynaecological Oncology Unit database and electronic records, and analysed using descriptive statistics. RESULTS: During the study period, 409 patients were diagnosed with EC, with an over-representation of Pacific Islanders (32.5%). Of these, 82.6% underwent MMR IHC testing, 20% were MMR-deficient (MMRd), and 71% had somatic hypermethylation. The Pacific Islander population had a 64% (odds ratio 0.36, P = 0.005) reduction in the odds of having MMRd tumours compared with Europeans. Of the patients who underwent MMR IHC testing, 5.5% were referred to a genetic clinic for germline testing. LS was confirmed in eight patients (2.3%). CONCLUSION: LS was diagnosed in 2.3% of patients. There was an over-representation of Pacific Islanders in the EC group but not among those diagnosed with LS.

ZBTB7A regulates LncRNA HOTAIR-mediated ELAVL1/SOX17 axis to inhibit malignancy and angiogenesis in endometrial carcinoma.

BACKGROUND: Endometrial cancer (EC) is the sixth most frequent cancer in women worldwide and has higher fatality rates. The pathophysiology of EC is complex, and there are currently no reliable methods for diagnosing and treating the condition. Long non-coding RNA (lncRNA), according to mounting evidence, is vital to the pathophysiology of EC. HOTAIR is regarded as a significant prognostic indicator of EC. ZBTB7A decreased EC proliferation and migration, according to recent studies, however the underlying mechanism still needs to be clarified. METHODS: The research utilized RT-qPCR to measure HOTAIR expression in clinical EC tissues and various EC cell lines. Kaplan-Meier survival analysis was employed to correlate HOTAIR levels with patient prognosis. Additionally, the study examined the interaction between ZBTB7A and HOTAIR using bioinformatics tools and ChIP assays. The experimental approach also involved manipulating the expression levels of HOTAIR and ZBTB7A in EC cell lines and assessing the impact on various cellular processes and gene expression. RESULTS: The study found significantly higher levels of HOTAIR in EC tissues compared to adjacent normal tissues, with high HOTAIR expression correlating with poorer survival rates and advanced cancer characteristics. EC cell lines like HEC-1 A and KLE showed higher HOTAIR levels compared to normal cells. Knockdown of HOTAIR in these cell lines reduced proliferation, angiogenesis, and migration. ZBTB7A was found to be inversely correlated with HOTAIR, and its overexpression led to a decrease in HOTAIR levels and a reduction in malignant cell behaviors. The study also uncovered that HOTAIR interacts with ELAVL1 to regulate SOX17, which in turn activates the Wnt/ß-catenin pathway, promoting malignant behaviors in EC cells. CONCLUSION: HOTAIR is a critical regulator in EC, contributing to tumor growth and poor prognosis. Its interaction with ZBTB7A and regulation of SOX17 via the Wnt/ß-catenin pathway underlines its potential as a therapeutic target.

Whole exome sequencing reveals diverse genomic relatedness between paired concurrent endometrial and ovarian carcinomas.

INTRODUCTION: Concurrent non-serous endometrial and ovarian tumours are often managed clinically as two separate primary tumours, but almost all exhibit evidence of a genomic relationship. METHODOLOGY: This study investigates the extent of relatedness using whole exome sequencing, which was performed on paired non-serous endometrial and ovarian carcinomas from 27 patients with concurrent tumours in a cohort with detailed clinicopathological annotation. Four whole exome sequencing-derived parameters (mutation, mutational burden, mutational signatures and mutant allele tumour heterogeneity scores) were used to develop a novel unsupervised model for the assessment of genomic similarity to infer genomic relatedness of paired tumours. RESULTS: This novel model demonstrated genomic relatedness across all four parameters in all tumour pairs. Mutations in PTEN, ARID1A, CTNNB1, KMT2D and PIK3CA occurred most frequently and 24 of 27 (89 %) tumour pairs shared identical mutations in at least one of these genes, with all pairs sharing mutations in a number of other genes. Ovarian endometriosis, CTNNB1 exon 3 mutation, and progression and death from disease were present across the similarity ranking. Mismatch repair deficiency was associated with less genomically similar pairs. DISCUSSION: Although there was diversity across the cohort, the presence of genomic similarity in all paired tumours supports the hypothesis that concurrent non-serous endometrial and ovarian carcinomas are genomically related and may have arisen from a common origin.

Performance of the Idylla microsatellite instability test in endometrial cancer.

CONTEXT: DNA mismatch repair (MMR) deficiency (dMMR) testing is now recommended in endometrial cancer. Defect identification in the molecules participating in this pathway, or the presence of microsatellite instability, are commonly employed for this purpose. Novel methods are continuously evolving to report dMMR/microsatellite instability and to easily perform routine diagnoses. OBJECTIVE: The main aim of this study was to compare the concordance of the Idylla microsatellite instability test for the identification of dMMR endometrial cancer samples defined by immunohistochemistry and MMR genomic status. DESIGN: We applied the Idylla MSI test to 126 early-stage endometrial cancer cases with MMR testing by immunohistochemistry and genomic characterization (methylation in MLH1 and sequence alterations in MLH1, PMS2, MSH2 and MSH6). Individual markers and overall specific performance indicators were explored. RESULTS: The Idylla platform achieved a higher global concordance rate with MMR genomic status than with immunohistochemistry (75 % and 66 %, respectively). Sensitivity and specificity are also higher (75 % vs 66 % and 96 % vs 90 %, respectively). Clustering analysis split the patients into 2 well-differentiated clusters, the pMMR and the dMMR group, represented by MLH1/PMS2 loss and the MLH1 methylated promoter. Overall, immunohistochemistry and MMR genomic status identified more dMMR cases than did the Idylla test, although correlations were improved with a modified Idylla test cut-off. CONCLUSIONS: Performance of the Idylla test was better correlated with MMR genomic status than MMR immunohistochemistry status, which improved with a modified test cut-off. Further studies are needed to confirm the cut-off accuracy.

Early detection of uterine corpus endometrial carcinoma utilizing plasma cfDNA fragmentomics.

BACKGROUND: Uterine corpus endometrial carcinoma (UCEC) is a prevalent gynecologic malignancy with a favorable prognosis if detected early. However, there is a lack of accurate and reliable early detection tests for UCEC. This study aims to develop a precise and non-invasive diagnostic method for UCEC using circulating cell-free DNA (cfDNA) fragmentomics. METHODS: Peripheral blood samples were collected from all participants, and cfDNA was extracted for analysis. Low-coverage whole-genome sequencing was performed to obtain cfDNA fragmentomics data. A robust machine learning model was developed using these features to differentiate between UCEC and healthy conditions. RESULTS: The cfDNA fragmentomics-based model showed high predictive power for UCEC detection in training (n = 133; AUC 0.991) and validation cohorts (n = 89; AUC 0.994). The model manifested a specificity of 95.5% and a sensitivity of 98.5% in the training cohort, and a specificity of 95.5% and a sensitivity of 97.8% in the validation cohort. Physiological variables and preanalytical procedures had no significant impact on the classifier's outcomes. In terms of clinical benefit, our model would identify 99% of Chinese UCEC patients at stage I, compared to 21% under standard care, potentially raising the 5-year survival rate from 84 to 95%. CONCLUSION: This study presents a novel approach for the early detection of UCEC using cfDNA fragmentomics and machine learning showing promising sensitivity and specificity. Using this model in clinical practice could significantly improve UCEC management and control, enabling early intervention and better patient outcomes. Further optimization and validation of this approach are warranted to establish its clinical utility.

Nomogram for predicting pathology upstaging in patients with EIN: is sentinel lymph node assessment useful in these patients?

OBJECTIVE: The objective of this study was to identify the risk factors for postoperative pathological escalation of endometrial cancer in patients with a pathologic diagnosis of endometrial intraepithelial neoplasia (EIN) before surgery. Some of the clues from the preoperative assessment were used to build a nomogram to predict the likely pathological escalation after surgery, and to explore the feasibility of sentinel lymph node biopsy in these patients with possible pathological escalation. METHODS: This was a retrospective analysis of patients who underwent surgical treatment for EIN diagnosed before surgery between 2018 and 2023 in The Obstetrics and Gynecology Hospital of Fudan University. parameters including clinical, radiological and histopathological factors were analyzed by univariate and multivariate logistic regression to determine the correlation with pathology upstaging. A nomogram based on the multivariate results was developed to predict the probability of pathology upstaging. A total of 729 patients were included, divided into training set and validation set. 484 patients were used to build the model. This nomogram was subsequently validated using 245 patients. RESULTS: Upstaging to endometrial carcinoma occurred in 115 (23.8 percent) of 484 women treated between 2018 and 2023 in training set. A lager endometrial thickness (at least 15 mm), menopause, hypertension, HE4, and endometrial blood were significantly associated with upstaging. A nomogram developed using these factors demonstrated good predictive performance (area under the receiver operating characteristic curve (AUC)=0.6808; 95% confidence interval [CI]=0.6246-0.7369). The nomogram showed similar predictive performance in the validation data set, based on another 245 women (AUC=0.7821; 95% CI=0.7076-0.8567). CONCLUSION: This study developed a novel nomogram based on the 5 most important factors, which can accurately predict invasive cancer. It is common for women with preoperative diagnosis of EIN to experience pathological progression to endometrial cancer. For some patients with postoperative pathological escalation, we found lymph node metastasis. This nomogram may be useful to help doctor decide whether to perform sentinel lymph node biopsy for surgical staging in these EIN patients. According to the nomogram, simultaneous sentinel lymph node biopsy in patients with high probability of postoperative pathological upgrading can provide better guidance for postoperative adjuvant treatment of endometrial cancer and avoid the occurrence of secondary surgery.