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Background: Around 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes. Methods: This study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence. Ethics and dissemination: The protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association's Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal. Conclusions: Prospective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH. Trial registration number: Chinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is the most lethal and endometrial cancer the most common gynaecological cancer in the UK, yet neither have a screening program in place to facilitate early disease detection. The aim is to evaluate whether online search data can be used to differentiate between individuals with malignant and benign gynaecological diagnoses. Methods: This is a prospective cohort study evaluating online search data in symptomatic individuals (Google user) referred from primary care (GP) with a suspected cancer to a London Hospital (UK) between December 2020 and June 2022. Informed written consent was obtained and online search data was extracted via Google takeout and anonymised. A health filter was applied to extract health-related terms for 24 months prior to GP referral. A predictive model (outcome: malignancy) was developed using (1) search queries (terms model) and (2) categorised search queries (categories model). Area under the ROC curve (AUC) was used to evaluate model performance. 844 women were approached, 652 were eligible to participate and 392 were recruited. Of those recruited, 108 did not complete enrollment, 12 withdrew and 37 were excluded as they did not track Google searches or had an empty search history, leaving a cohort of 235. Results: The cohort had a median age of 53 years old (range 20–81) and a malignancy rate of 26.0%. There was a difference in online search data between those with a benign and malignant diagnosis, noted as early as 360 days in advance of GP referral, when search queries were used directly, but only 60 days in advance, when queries were divided into health categories. A model using online search data from patients (n = 153) who performed health-related search and corrected for sample size, achieved its highest sample-corrected AUC of 0.82, 60 days prior to GP referral. Conclusions: Online search data appears to be different between individuals with malignant and benign gynaecological conditions, with a signal observed in advance of GP referral date. Online search data needs to be evaluated in a larger dataset to determine its value as an early disease detection tool and whether its use leads to improved clinical outcomes. [ABSTRACT FROM AUTHOR]

Background Endometrial cancer is a prevalent gynecologic malignancy found in postmenopausal women. However, in the last two decades, the incidence of early-stage has doubled in women under 40 years old. This study aimed to investigate the clinical and pathological characteristics and adjuvant therapeutic modalities of both young and not -young patients with early-stage endometrial cancer in China’s real world. Methods This retrospective study analyzed patients with early-stage endometrial cancer at 13 medical institutions in China from 1999 to 2015. The patients were divided into two groups: young (≤45 years old) and non-young (>45 years old). Statistical comparisons were conducted between the two groups for clinical characteristics, pathological features, and survival. The study also identified factors that affect local recurrence-free survival (LRFS) using Cox proportional risk regression analysis. Propensity score matching (1:1) was used to compare the effects of local control between vaginal brachytherapy (VBT) alone and pelvic external beam radiotherapy (EBRT)±VBT. Results The study involved 1,280 patients, 150 of whom were 45 years old or younger. The young group exhibited a significantly higher proportion of stage II, low-risk, lower uterine segment infiltration (LUSI), and cervical invasion compared to the non-young group. Additionally, the young patients had significantly larger maximum tumor diameters. The young group also had a significantly higher five-year overall survival (OS) and a five-year LRFS. Age is an independent risk factor for LRFS. There was no significant difference in LRFS between young patients with intermediate- to high-risk early-stage endometrial cancer who received EBRT±VBT and those who received VBT alone. Conclusions In the present study, young patients had better characteristics than the non-young group, while they exhibited higher levels of aggressiveness in certain aspects. The LRFS and OS outcomes were better in young patients. Age is an independent risk factor for LRFS. Additionally, VBT alone may be a suitable option for patients under 45 years of age with intermediate- to high-risk early-stage endometrial cancer, as it reduces the risk of toxic reactions and future second cancers while maintaining similar local control as EBRT. [ABSTRACT FROM AUTHOR]

Background: This study aimed to report clinical practice patterns of postoperative radiotherapy for stage I to II endometrial carcinoma (EC) patients treated in 13 Chinese medical centers. Methods: We included early stage EC patients treated by hysterectomy and adjuvant RT between 2003 and 2017 from 13 institutions. Patients were classified into 4 risk groups based on ESMO-ESGO-ESTRO recommendations (2014). Results: A total of 1,227 cases were analyzed. Along the 15 years of the study, an increasing tendency was found towards administration for vaginal brachytherapy (VBT) alone, while the proportion of external beam pelvic radiotherapy (EBRT) alone remained stable in the corresponding period. When radiation modalities were stratified by risk groups, proportion of VBT alone significantly increased in all risk groups. The higher the risk, the later VBT became the main adjuvant treatment modality. However, EBRT alone or with VBT remained the main adjuvant method for high-risk patients. There were 13 dose-fractionation schemes for VBT alone with the scheme of 30 Gy in 6 fractions prescribed at 0.5cm under the vaginal mucosa accounting for most. There were 17 schemes for VBT boost and the most common schedule was 10 Gy in 2 fractions. The upper 3–5cm part of vagina was the most frequent target. 89.6% of the practitioners performed two-dimensional VBT technique. The median dose for EBRT was 50 Gy. From 2003 to 2017, conventional radiotherapy was gradually replaced by three-dimensional conformal radiotherapy modality and intensity modulated radiotherapy. Conclusion: We report a significant shift from EBRT to VBT alone for high-intermediate-risk, intermediate-risk and low-risk EC patients from 2003 to 2017 while EBRT remained the main radiation modality for high-risk early stage patients. There has been remarkable heterogeneity among VBT dose fractionation schedules across China. Trial registration: The clinical trial ID was ChiCTR-PRC-17010712. It was authorized by the Institutional Review Board of Peking Union Medical College Hospital (N0. S-K139). [ABSTRACT FROM AUTHOR]

Background: Endometrial carcinomas are the most common female genital malignancies. They are very rare in pregnancy and worldwide less than 60 cases associated with pregnancy are published. No clear cell carcinoma has been described in a pregnancy with a live birth. Case presentation: We present the course of a 43-year-old Uyghur female patient with the diagnosis of endometrial carcinoma with a deficiency in the DNA mismatch repair system in the pregnancy. The malignancy with clear cell histology was confirmed by biopsy following the delivery via caesarean section due to preterm birth of a fetus with sonographically suspected tetralogy of Fallot. Earlier whole exome sequencing after amniocentesis had shown a heterozygous mutation in the MSH2 gene, which was unlikely to be related to the fetal cardiac defect. The uterine mass was initially deemed an isthmocervical fibroid by ultrasound and was confirmed as stage II endometrial carcinoma. The patient was consequently treated with surgery, radiotherapy and chemotherapy. Six months after the adjuvant therapy, re-laparotomy was performed due to ileus symptoms and an ileum metastasis was found. The patient is currently undergoing immune checkpoint inhibitor therapy with pembrolizumab. Conclusion: Rare endometrial carcinoma should be included in the differential diagnosis of uterine masses in pregnant women with risk factors. [ABSTRACT FROM AUTHOR]

Background: Pre-eclampsia may be associated with the development of endometrial cancer; however, previous findings have been conflicting. Objectives: To investigate if pre-eclampsia is associated with an increased risk of endometrial cancer. Method: Two independent reviewers screened titles and abstracts of studies identified in MEDLINE, Embase, and Web of Science databases from inception until March 2022. Studies were included if they investigated pre-eclampsia and subsequent risk of endometrial cancer (or precursor lesions). Random-effects meta-analysis was used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between pre-eclampsia during pregnancy and endometrial cancer risk. Main results: There were seven articles identified which investigated endometrial cancer, of which one also investigated endometrial cancer precursors. Overall, the studies include 11,724 endometrial cancer cases. No association was observed between pre-eclampsia and risk of endometrial cancer with moderate heterogeneity observed (pooled HR 1.07, 95% CI 0.79–1.46, I2 = 34.1%). In sensitivity analysis investigating risk of endometrial neoplasia (atypical hyperplasia, carcinoma in situ, or cancer), there was some evidence that pre-eclampsia was associated with an increased risk (HR 1.34, 95% CI 1.15–1.57, I2 = 29.6%). Conclusions: Pre-eclampsia was not associated with an increased risk of endometrial cancer. Additional large studies with information on pre-eclampsia sub-type aiming to investigate endometrial cancer precursor conditions are merited. [ABSTRACT FROM AUTHOR]

Background: To evaluate the oncological outcomes and the impact of clinicopathological factors on endometrial clear cell carcinoma (ECCC) outcomes. Methods: Medical records of patients with primary ECCC treated at our center between 1985 and December 2020 were reviewed. Overall survival (OS) and progression-free survival (PFS) were the endpoints. The Kaplan–Meier method and Cox regression analysis were used. Results: In total, 156 patients were included, of whom 59% and 41% had early- and advanced-stage ECCC, respectively. The median age of onset was 61 years, and 80.8% of the patients were postmenopausal. Ninety-two (59%) and 64 (41%) patients had pure ECCC and mixed endometrial carcinoma with clear cell carcinoma (CCC) components, respectively. Mixed pathological components, elevated cancer antigen 125 levels, positive lymphovascular space invasion, deep myometrial invasion, and malignant peritoneal washing cytology (PWC) were more frequently observed in the advanced stage. Thirty-nine patients (25%) experienced relapse and 32 patients (20.5%) died. The 5-year PFS and OS rates for the entire cohort were 72.6% and 79%, respectively. Multivariate analysis showed that advanced-stage disease and positive PWC significantly decreased PFS, while advanced-stage disease and older age (> 61 years) significantly decreased OS. Conclusions: ECCC is a rare and aggressive type II endometrial carcinoma that is common in older women and patients with advanced-stage disease. Positive PWC was associated with decreased PFS, although its presence did not influence the stage. Positive PWC, and advanced stage and older age were independent negative prognostic factors. [ABSTRACT FROM AUTHOR]

Background: The ZC3H7B-BCOR fusion gene has recently been described in tumours with kinship to so-called high grade endometrial stromal sarcoma (HG-ESS). This subset of tumour behaves similarly to YWHAE-NUTM2A/B HG-ESS, however, they are both morphologically and immunophenotypically distinct neoplasms. The identified rearrangements in the BCOR gene have been accepted as both the driver and requisite feature in creating a novel sub-entity within the category of HG-ESS. Preliminary investigations into BCOR HG-ESS have shown similar outcomes to YWHAE-NUTM2A/B HG-ESS, with patients typically presenting with high stage disease. Clinical recurrences and metastases to lymph nodes, sacrum/bone, pelvis/peritoneum, lung, bowel and skin have been identified. In this report, we describe a case of BCOR HG-ESS, that is deeply myoinvasive and widely metastatic. Metastatic deposits include a mass in the breast discovered on self-examination; a metastatic site that has yet to be reported in the literature. Case presentation: A 59-year-old female underwent biopsy for post-menopausal bleeding, yielding a diagnosis of "low-grade spindle cell neoplasm with myxoid stroma and endometrial glands", favouring endometrial stromal sarcoma (ESS). She was then referred for total hysterectomy and bilateral salpingo-oophorectomy. The resected uterine neoplasm was both intracavitary and deeply myoinvasive with morphology consistent with that of the biopsy specimen. Characteristic immunohistochemistry (IHC) was noted, and fluorescence in situ hybridization confirmed BCOR rearrangement, supporting a diagnosis of BCOR HG-ESS. A few months postoperatively, the patient underwent needle core biopsy of the breast which revealed metastatic HG-ESS. Conclusions: This case highlights some of the diagnostic challenges posed by uterine mesenchymal neoplasms, and exemplifies the emerging histomorphologic, immunohistochemical, molecular and clinicopathologic features of the recently described HG-ESS with ZC3H7B-BCOR fusion. It adds to the body of evidence supporting the inclusion of BCOR HG-ESS as a sub-entity of HG-ESS within the endometrial stromal and related tumours subcategory of uterine mesenchymal tumors, as well as the poor prognosis and high metastatic potential of this tumor. [ABSTRACT FROM AUTHOR]

Background: To assess the value of whole-lesion apparent diffusion coefficient (ADC) histogram analysis in differentiating stage IA endometrial carcinoma (EC) from benign endometrial lesions (BELs) and characterizing histopathologic features of stage IA EC preoperatively. Methods: One hundred and six BEL and 126 stage IA EC patients were retrospectively enrolled. Eighteen volumetric histogram parameters were extracted from the ADC map of each lesion. The Mann–Whitney U or Student's t-test was used to compare the differences between the two groups. Models based on clinical parameters and histogram features were established using multivariate logistic regression. Receiver operating characteristic (ROC) analysis and calibration curves were used to assess the models. Results: Stage IA EC showed lower ADC10th, ADC90th, ADCmin, ADCmax, ADCmean, ADCmedian, interquartile range, mean absolute deviation, robust mean absolute deviation (rMAD), root mean squared, energy, total energy, entropy, variance, and higher skewness, kurtosis and uniformity than BELs (all p < 0.05). ADCmedian yielded the highest area under the ROC curve (AUC) of 0.928 (95% confidence interval [CI] 0.895–0.960; cut-off value = 1.161 × 10−3 mm2/s) for differentiating stage IA EC from BELs. Moreover, multivariate analysis demonstrated that ADC-score (ADC10th + skewness + rMAD + total energy) was the only significant independent predictor (OR = 2.641, 95% CI 2.045–3.411; p < 0.001) for stage IA EC when considering clinical parameters. This ADC histogram model (ADC-score) achieved an AUC of 0.941 and a bias-corrected AUC of 0.937 after bootstrap resampling. The model performed well for both premenopausal (accuracy = 0.871) and postmenopausal (accuracy = 0.905) patients. Besides, ADCmin and ADC10th were significantly lower in Grade 3 than in Grade 1/2 stage IA EC (p = 0.022 and 0.047). At the same time, no correlation was found between ADC histogram parameters and the expression of Ki-67 in stage IA EC (all p > 0.05). Conclusions: Whole-lesion ADC histogram analysis could serve as an imaging biomarker for differentiating stage IA EC from BELs and assisting in tumor grading of stage IA EC, thus facilitating personalized clinical management for premenopausal and postmenopausal patients. [ABSTRACT FROM AUTHOR]

Background: Progestin is used for fertility-sparing treatment in cases of endometrial cancer (EC). Progestin can induce hyperprolactinemia by increasing pituitary secretion and endometrial decidualization. However, progestin induces prolactin (PRL) secretion, which stimulates cell proliferation and deleteriously affects treatment. To date, the detrimental effect of PRL, the secretion of which is induced by medroxyprogesterone acetate (MPA) during fertility-sparing treatment, has not yet been fully elucidated. Therefore, we aimed to assess the effects of PRL on EC cells during combined treatment with progestin and metformin.Methods: In total, 71 patients with EC/endometrial atypical hyperplasia who underwent fertility-sparing treatment at our institution from 2009-2019 were enrolled. Serum PRL levels were determined using enzyme immunoassays; mRNA levels in endometrial tissues were determined using quantitative reverse-transcription PCR. To evaluate MPA-induced decidualization, cancer-associated stromal cells were enzymatically released from surgically removed specimens of six patients with EC. To examine PRL-induced cell proliferation, the EC cell lines Ishikawa, HEC1B, and HEC265 were used. In vitro cell proliferation was evaluated using the WST assay; protein levels of signaling molecules were determined using western blotting.Results: MPA administration significantly increased serum PRL levels at 3 and 6 months and upregulated IGFBP-1 and PRL mRNA expression in tissues at 3 months of fertility-sparing treatment. Metformin significantly reduced MPA-induced IGFBP-1 and PRL mRNA expression during fertility-sparing treatment and significantly inhibited the upregulation of IGFBP-1 and PRL mRNA and PRL levels due to decidualization induced by MPA and cAMP treatment in primary cultured EC stromal cells. In vitro, PRL increased cell proliferation and ERK1/2 phosphorylation levels, whereas metformin attenuated these increases.Conclusions: MPA upregulated PRL levels in serum and endometrial tissues during fertility-sparing treatment. Metformin co-administration reduced PRL production and attenuated PRL-induced cell-proliferation activity. This study may provide valuable insights on the application of metformin to improve the outcomes of fertility-sparing treatment. [ABSTRACT FROM AUTHOR]

Background: This research aimed to provide an overview of the impact of adjuvant vaginal brachytherapy (VBT) and external beam pelvic radiotherapy (EBRT) with or without VBT on survival in stage I to II EC patients in China from a long-term multi-institutional analysis.Methods: We retrospectively analyzed stage I to II EC patients from 13 institutions treated between 2003 and 2015. All patients underwent surgical staging and received adjuvant RT. Patients were divided into groups of low-risk (LR), intermediate-risk (IR), high-intermediate-risk (HIR) and high-risk (HR). Survival statistics, failure pattern, and toxicity of different radiation modalities in different risk groups were analyzed.Results: A total of 1048 patients were included. HR disease represented 27.6%, HIR 17.7%, IR 27.7% and LR 27.1%, respectively. Endometrioid adenocarcinoma (EAC) and non-endometrioid carcinoma (NEC) accounted for 92.8 and 7.2%. A total of 474 patients received VBT alone and 574 patients received EBRT with or without VBT. As for EAC patients, the 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rate was: 94.6, 90.4, 93.0 and 91.6%, respectively. For LR patients, EBRT (with or without VBT) seemed to be a risk factor. With the higher risk category, the survival benefit of EBRT gradually became remarkable. EBRT (with or without VBT) significantly increased DFS, LRFS and DMFS compared to VBT alone in the HR group (p < 0.05). Distant metastasis was the main failure pattern for all risk groups. As for NEC patients, the 5-year OS, DFS, LRFS and DMFS rate was: 93.4, 87.2, 91.7 and 89.3%, respectively. As for toxicity, EBRT (with or without VBT) significantly increased the incidence of grade 1-2 gastrointestinal, urinary, and hematological toxicity.Conclusions: For stage I to II EC patients, EAC accounted for the majority and had better prognosis than NEC. For EAC patients, VBT alone resulted in comparable survival to EBRT in the LR, IR and HIR groups, while EBRT significantly increased survival in the HR group. EBRT had higher rate of toxicity than VBT. [ABSTRACT FROM AUTHOR]

Background: To identify predictive value of apparent diffusion coefficient (ADC) values and magnetic resonance imaging (MRI)-based radiomics for all recurrences in patients with endometrial carcinoma (EC).Methods: One hundred and seventy-four EC patients who were treated with operation and followed up in our institution were retrospectively reviewed, and the patients were divided into training and test group. Baseline clinicopathological features and mean ADC (ADCmean), minimum ADC (ADCmin), and maximum ADC (ADCmax) were analyzed. Radiomic parameters were extracted on T2 weighted images and screened by logistic regression, and then a radiomics signature was developed to calculate the radiomic score (radscore). In training group, Kaplan-Meier analysis was performed and a Cox regression model was used to evaluate the correlation between clinicopathological features, ADC values and radscore with recurrence, and verified in the test group.Results: ADCmean showed inverse correlation with recurrence, while radscore was positively associated with recurrence. In univariate analyses, FIGO stage, pathological types, myometrial invasion, ADCmean, ADCmin and radscore were associated with recurrence. In the training group, multivariate Cox analysis showed that pathological types, ADCmean and radscore were independent risk factors for recurrence, which were verified in the test group.Conclusions: ADCmean value and radscore were independent predictors of recurrence of EC, which can supplement prognostic information in addition to clinicopathological information and provide basis for individualized treatment and follow-up plan. [ABSTRACT FROM AUTHOR]

Backgrounds: We aimed to evaluate the prognosis in patients with synchronous endometrial and ovarian cancer (SEOC) by comparing the differences between double primary cancer (DPC) and metastatic cancer (MC).Methods: The medical records of 47 patients diagnosed synchronously with endometrial and ovarian cancer between January 2006 and December 2018 were retrospectively reviewed. Twenty-eight and 19 patients were diagnosed with DPC and MC, respectively. Demographics, recurrence-free survival (RFS), and 5-year overall survival (OS) were compared. The clinical factors affecting survival were evaluated using univariate and multivariate analyses.Results: The demographics were not different between both groups. Endometrioid histology and the International Federation of Gynecology and Obstetrics grade were higher in the MC group than in the DPC group (42.1% vs. 10.7%; P = 0.018, P = 0.002, respectively). The ratio of post-operative adjuvant therapy was not different in both groups. Recurrence occurred in five patients with DPC and seven with MC. The difference in RFS was not significantly different (P = 0.131) but the OS was different between both groups (P = 0.020). Histology and para-aortic lymph node metastasis were associated wtih RFS in univariate analysis, but no difference was found in multivariate analysis.Conclusions: Although DPC patients had longer OS, multivariate analysis did not identify any influential factors. Focus should be placed on defining the appropriate adjuvant treatment for high-risk patients, which will improve prognosis, rather than on discriminating between DPC and MC. [ABSTRACT FROM AUTHOR]

Background: Matricellular glycoprotein, SPARC is a secreted molecule, that mediates the interaction between cells and extracellular matrix. SPARC functions as a regulator of matrix organization and modulates cell behavior. In various kinds of cancer, strong SPARC expression was observed in stromal tissues as well as in cancer epithelial cells. The function of SPARC in cancer cells is somewhat controversial and its impact on peritumoral stromal cells remains to be resolved.Methods: We investigated the effects of SPARC expression in endometrial cancer cells on the surrounding stromal fibroblasts using in vitro co-culture system. Changes in characteristics of fibroblasts were examined by analysis of fibroblast-specific markers and in vitro contraction assay.Results: SPARC induced AKT phosphorylation and epithelial-to-mesenchymal transition, consistent with previous reports. Cancer-associated fibroblasts of endometrial cancer expressed higher levels of mesenchymal- and fibroblast-associated factors and had a stronger contraction ability. Unexpectedly, cancer-associated fibroblasts expressed comparable levels of SPARC compared with fibroblasts from normal endometrium. However, co-culture of normal fibroblasts with SPARC-expressing Ishikawa cells resulted in activation of the fibroblasts. Immunodepletion of SPARC did not affect the activation of fibroblasts.Conclusions: Our data indicated that SPARC activated fibroblasts only in the presence of fibronectin, which was abundantly secreted from SPARC-expressing endometrial cancer cells. These results suggested that a SPARC-fibronectin-mediated activation of fibroblasts might be involved in enhanced mobility and invasion of cancer cells. [ABSTRACT FROM AUTHOR]

Background: Aberrant DNA methylation is a vital molecular alteration commonly detected in type I endometrial cancers (EC), and tet methylcytosine dioxygenase 2 (TET2) and 5-hydroxymethylcytosine (5hmC) play significant roles in DNA demethylation. However, little is known about the function and correlation of TET2 and 5hmC co-expressed in EC. This study intended to investigate the clinical significance of TET2 and 5hmC in EC., Methods: The levels of TET2 and 5hmC were detected in 326 endometrial tissues by immumohistochemistry, and the correlation of their level was detected by Pearson analysis. The association between the levels of TET2 and 5hmC and clinicopathologic characteristics was analyzed. Prognostic value of TET2 and 5hmC was explored by Kaplan-Meier analysis. The Cox proportional hazard regression model was used for univariate and multivariate analyses., Results: Based on the analysis results, TET2 protein level was positively correlated with 5hmC level in EC tissues (r = 0.801, P < 0.001). TET2 + 5hmC + (high TET2 and high 5hmC) association was significantly associated with well differentiation, myometrial invasion, negative lymph node metastasis, and tumor stage in EC. Association of TET2 and 5hmC was confirmed as a prognostic factor (HR = 2.843, 95%CI = 1.226-3.605, P = 0.007) for EC patients, and EC patients with TET2 - 5hmC - level had poor overall survival., Conclusions: In summary, the association of TET2 and 5hmC was downregulated in EC tissues, and may be a potential poor prognostic indicator for EC patients. Combined detection of TET2 and 5hmC may be valuable for the diagnosis and prognosis of EC., (© 2024. The Author(s).)

Background: When endometrial carcinoma invades the cervical stroma, overall survival and disease-free survival decrease. However, it is still controversial whether patients in suspected stage II should be treated with radical hysterectomy. The goal of this study is to describe the role of radical hysterectomy in patients with endometrial carcinoma and cervical involvement. Methods: This was a retrospective cohort study were a total of 239 patients with endometrial carcinoma with cervical involvement from Mexico City's National Cancer Institute were divided according to the type of hysterectomy, and the outcomes were compared using statistical analysis. Results: The 5-year overall survival was 75.76% for the simple hysterectomy group and 89.19% for the radical hysterectomy group, without achieving statistical significance. The 5-year disease-free survival was 72.95% for the simple hysterectomy group and 64.31% for the radical hysterectomy group, without achieving statistical significance. Radicality was associated with longer surgical times, intraoperative complications, and bleeding over 500 ml. Conclusions: In patients with endometrial carcinoma with cervical involvement, radical hysterectomy does not improve prognosis or alter adjuvant therapy. [ABSTRACT FROM AUTHOR]

Background: FLT-PET/CT can accurately identify and locate functional bone marrow (FBM) with hematopoietic capability, the FBM were divided into two levels as FBM 1 (strongest hemopoietic ability region)and FBM 2 (moderate hemopoietic ability region) via FLT-PET/CT. The purpose of this study was to explore the relationship between dose-volume parameters of pelvic FBM and hematologic toxicity (HT) during radiotherapy with or without concurrent chemotherapy for uterine cervical/endometrial cancer., Methods: From December 2016 to September 2021, ninety-seven uterine cervical/endometrial cancer patients received intensity-modulated radiation therapy were prospectively recruited in this single-arm, prospective, phase II trial. Blood counts were reviewed weekly during radiotherapy. Single- and multifactor regression methods were used to analyze the relationships between dose-volume parameters of FBM 1/2 and grade ≥ 2 HT. ROC curves were used to determine the cutoff values for the dose-volume parameters of FBM 1/2 ., Results: The incidence of grade ≥ 2 leukopenia, neutropenia, thrombocytopenia and anemia in patients during radiotherapy was 63.9%, 45.4%, 19.6% and 38.8% respectively, and the median occurrence time was the 29th, 42th, 35th and 31th day, respectively. Multivariate regression analysis showed that the D max of FBM 1 was significantly related to grade ≥ 2 leukopenia (OR = 1.277 95% CI 1.067-1.528, P = 0.008), D mean of FBM 2 was significantly related to grade ≥ 2 thrombocytopenia (OR = 1.262 95% CI 1.066-1.494, P = 0.007), and V 10 of FBM 1 was significantly related to grade ≥ 2 anemia (OR = 1.198 95% CI 1.003-1.431, P = 0.046). The incidence of grade ≥ 2 leukopenia for patients with FBM 1 D max < 53 Gy was lower than that for patients with FBM 1 D max ≥ 53 Gy (53.4% vs. 95.8%, P < 0.001). The incidence of grade ≥ 2 thrombocytopenia in patients with FBM 2 D mean < 33 Gy was lower than that in patients with FBM 2 D mean ≥ 33 Gy (0 vs. 28.4%, P < 0.001). The incidence of grade ≥ 2 anemia for patients with FBM 1 V 10  < 95% was lower than that in patients with FBM 1 V 10  ≥ 95% (24.4% vs. 57.1%, P = 0.003)., Conclusions: Grade ≥ 2 HT usually occurs in the 4th week of radiotherapy for patients with uterine cervical/endometrial cancer. The D max and V 10 of FBM 1 and the D mean of FBM 2 were significantly associated with the occurrence of grade ≥ 2 HT. The recommended optimal dose constraints were FBM 1 D max < 53 Gy, V 10  < 95%, and FBM 2 D mean <33 Gy., (© 2023. The Author(s).)

Background: Several observational studies have explored the associations between Sjögren's syndrome (SS) and certain cancers. Nevertheless, the causal relationships remain unclear. Mendelian randomization (MR) method was used to investigate the causality between SS and different types of cancers., Methods: We conducted the two-sample Mendelian randomization with the public genome-wide association studies (GWASs) summary statistics in European population to evaluate the causality between SS and nine types of cancers. The sample size varies from 1080 to 372,373. The inverse variance weighted (IVW) method was used to estimate the causal effects. A Bonferroni-corrected threshold of P < 0.0031 was considered significant, and P value between 0.0031 and 0.05 was considered to be suggestive of an association. Sensitivity analysis was performed to validate the causality. Moreover, additional analysis was used to assess the associations between SS and well-accepted risk factors of cancers., Results: After correcting the heterogeneity and horizontal pleiotropy, the results indicated that patients with SS were significantly associated with an increased risk of lymphomas (odds ratio [OR] = 1.0010, 95% confidence interval [CI]: 1.0005-1.0015, P = 0.0002) and reduced risks of prostate cancer (OR = 0.9972, 95% CI: 0.9960-0.9985, P = 2.45 × 10 -5 ) and endometrial cancer (OR = 0.9414, 95% CI: 0.9158-0.9676, P = 1.65 × 10 -5 ). Suggestive associations were found in liver and bile duct cancer (OR = 0.9999, 95% CI: 0.9997-1.0000, P = 0.0291) and cancer of urinary tract (OR = 0.9996, 95% CI: 0.9992-1.0000, P = 0.0281). No causal effect of SS on other cancer types was detected. Additional MR analysis indicated that causal effects between SS and cancers were not mediated by the well-accepted risk factors of cancers. No evidence of the causal relationship was observed for cancers on SS., Conclusions: SS had significant causal relationships with lymphomas, prostate cancer, and endometrial cancer, and suggestive evidence of association was found in liver and bile duct cancer and cancer of urinary tract, indicating that SS may play a vital role in the incidence of these malignancies., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Somatic amplifications of the LYL1 gene are relatively common occurrences in patients who develop uterine corpus endometrial carcinoma (UCEC) as opposed to other cancers. This study was undertaken to determine whether such genetic alterations affect survival outcomes of UCEC.Methods: In 370 patients with UCEC, we analysed clinicopathologic characteristics and corresponding genomic data from The Cancer Genome Atlas database. Patients were stratified according to LYL1 gene status, grouped as amplification or non-amplification. Heightened levels of cancer-related genes expressed in concert with LYL1 amplification were similarly investigated through differentially expressed gene and gene set enrichment analyses. Factors associated with survival outcomes were also identified.Results: Somatic LYL1 gene amplification was observed in 22 patients (5.9%) with UCEC. Patients displaying amplification (vs. non-amplification) were significantly older at the time of diagnosis and more often were marked by non-endometrioid, high-grade, or advanced disease. In survival analysis, the amplification subset showed poorer progression-free survival (PFS) and overall survival (OS) rates (3-year PFS: 34.4% vs. 79.9%, P = 0.031; 5-year OS: 25.1% vs. 84.9%, P = 0.014). However, multivariate analyses adjusted for tumor histologic type, grade, and stage did not confirm LYL1 gene amplification as an independent prognostic factor for either PFS or OS. Nevertheless, MAPK, WNT, and cell cycle pathways were significantly enriched by LYL1 gene amplification (P < 0.001, P = 0.002, and P = 0.004, respectively).Conclusions: Despite not being identified as an independent prognostic factor in UCEC, LYL1 gene amplification is associated with other poor prognostic factors and correlated with upregulation of cancer-related pathways. [ABSTRACT FROM AUTHOR]

Gene expression and posttranscriptional regulation can be strongly influenced by epigenetic modifications. N 6 -methyladenosine, the most extensive RNA modification, has been revealed to participate in many human diseases. Recently, the role of RNA epigenetic modifications in the pathophysiological mechanism of female reproductive diseases has been intensively studied. RNA m 6 A modification is involved in oogenesis, embryonic growth, and foetal development, as well as preeclampsia, miscarriage, endometriosis and adenomyosis, polycystic ovary syndrome, premature ovarian failure, and common gynaecological tumours such as cervical cancer, endometrial cancer, and ovarian cancer. In this review, we provide a summary of the research results of m 6 A on the female reproductive biology and pathophysiology in recent years and aim to discuss future research directions and clinical applications of m 6 A-related targets. Hopefully, this review will add to our understanding of the cellular mechanisms, diagnostic biomarkers, and underlying therapeutic strategies of female reproductive system diseases. Video Abstract., (© 2023. The Author(s).)

Endometrial cancer (EC) is a common gynecological cancer that endangers women health. Although substantial progresses of EC management have been achieved in recent years, the incidence of EC still remains high. Obesity has been a common phenomenon worldwide that increases the risk of EC. However, the mechanism associating obesity and EC has not been fully understood. Metabolic reprogramming as a remarkable characteristic of EC is currently emerging. As the primary factor of metabolic syndrome, obesity promotes insulin resistance, hyperinsulinemia and hyperglycaemia. This metabolic disorder remodels systemic status, which increases EC risk and is related with poor prognosis. Glucose metabolism in EC cells is complex and mediated by glycolysis and mitochondria to ensure energy requirement. Factors that affect glucose metabolism may have an impact on EC initiation and progression. In this study, we review the glucose metabolic reprogramming of EC not only systemic metabolism but also inherent tumor cell metabolism. In particular, the role of glucose metabolic regulation in malignant properties of EC will be focused. Understanding of metabolic profile and glucose metabolism-associated regulation mechanism in EC may provide novel perspective for treatment., (© 2023. The Author(s).)

Background: Observational epidemiological studies suggest a link between several factors related to ovulation and reproductive function and endometrial cancer (EC) risk; however, it is not clear whether these relationships are causal, and whether the risk factors act independently of each other. The aim of this study was to investigate putative causal relationships between the number of live births, age at last live birth, and years ovulating and EC risk.  METHODS: We conducted a series of observational analyses to investigate various risk factors and EC risk in the UK Biobank (UKBB). Additionally, multivariate analysis was performed to elucidate the relationship between the number of live births, age at last live birth, and years ovulating and other related factors such as age at natural menopause, age at menarche, and body mass index (BMI). Secondly, we used Mendelian randomization (MR) to assess if these observed relationships were causal. Genome-wide significant single nucleotide polymorphisms (SNPs) were extracted from previous studies of woman's number of live births, age at menopause and menarche, and BMI. We conducted a genome-wide association analysis using the UKBB to identify SNPs associated with years ovulating, years using the contraceptive pill, and age at last live birth., Results: We found evidence for a causal effect of the number of live births (inverse variance weighted (IVW) odds ratio (OR): 0.537, p = 0.006), the number of years ovulating (IVW OR: 1.051, p = 0.014), in addition to the known risk factors BMI, age at menarche, and age at menopause on EC risk in the univariate MR analyses. Due to the close relationships between these factors, we followed up with multivariable MR (MVMR) analysis. Results from the MVMR analysis showed that number of live births had a causal effect on EC risk (OR: 0.783, p = 0.036) independent of BMI, age at menarche and age at menopause., Conclusions: MVMR analysis showed that the number of live births causally reduced the risk of EC., (© 2022. The Author(s).)

Objective: Fertility-sparing treatment of atypical endometrial hyperplasia (AEH) and early endometrial carcinoma (EC) patients has recently emerged important social health topic. This study is designed to explore the risk factors for time to complete remission (CR) of fertility-sparing treatment in woman with AEH and early EC., Methods: A retrospective study was designed with clinical data from 106 patients admitted between January 2012 to December 2019. Univariate and multivariate logistic analysis were used to explore independent risk factors for time to CR. These factors were employed in receiver operator characteristic (ROC) curve and the decision curve analysis (DCA) to evaluate predictive accuracy of time to CR. Stratified analysis and interactive analysis was also performed for more in-depth perspective., Results: Univariate analysis showed that fasting blood glucose levels (FBG, OR = 1.6, 95%CI: 0.6-2.5, P = 0.020), metabolic syndrome (MetS, OR = 3.0, 95%CI: 1.1-5.0, P = 0.003), and polycystic ovary syndrome (PCOS, OR = 2.0, 95%CI: 0.5-3.4, P = 0.009) were associated with time to CR. Among these factors, multivariate analysis confirmed MetS (OR = 3.1, 95%CI: 1.0-5.2, P = 0.005) was an independent risk factor. The area under the ROC curve (AUC) of MetS was higher than FBG and PCOS (AUC = 0.723 vs 0.612 and 0.692). The AUC of FBG combined with PCOS was 0.779, and it was improved to 0.840 when MetS was included (P < 0.05). Additionally, MetS played different roles in time to CR in various groups. Moreover, we found high-density lipoprotein (HDL) and MetS had an interactive effect for time to CR., Conclusion: MetS is an independent risk factor for time to CR and should be taken seriously in fertility-sparing management of AEH and early EC patients., (© 2022. The Author(s).)