circRNA3669 promotes goat endometrial epithelial cells proliferation via miR-26a/RCN2 to activate PI3K/AKT-mTOR and MAPK pathways

The development of receptive endometrium(RE) from pre-receptive endometrium(PE) for successful embryo implantation is a complex dynamic process in which the morphology and physiological states of the endometrial epithelium undergo a series of significant changes, including cell proliferation and apoptosis. However, the molecular mechanisms are not yet fully understood. In this study, a higher circRNA3669 level was observed in PE than in RE of goats. Functional assays revealed that this overexpression promoted the proliferation of goat endometrial epithelial cells(GEECs) by activating the expression of genes related to the PI3K/AKT-mTOR and MAPK pathways,thereby inhibiting apoptosis in vitro. Furthermore, circRNA3669 functioned as a competing endogenous RNA(ceRNA) to upregulate Reticulocalbin-2(RCN2) expression at the post-transcriptional level by interacting with and downregulating miR-26a in GEECs. In addition, RCN2, which is highly expressed in the PE of goats, was found to be regulated by β-estradiol(E2) and progesterone(P4). Our results demonstrated that RCN2 also affected the key proteins PI3K, AKT, mTOR, JNK, and P38 in the PI3K/AKT-mTOR and MAPK pathways, thereby facilitating GEECs proliferation and suppressing their apoptosis in vitro. Collectively, we constructed a new circRNA3669-miR-26aRCN2 regulatory network in GEECs, which further provides strong evidence that circRNA could potentially play a crucial regulatory role in the development of RE in goats.

Antitumor Effect of Apcin on Endometrial Carcinoma via p21-Mediated Cell Cycle Arrest and Apoptosis

Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential target is cell division cycle 20(CDC20),which has been implicated in oncogenesis.This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved.Methods The effects of Apcin on EC cell proliferation,apoptosis,and the cell cycle were evaluated using CCK8 assays and flow cytometry.RNA sequencing(RNA-seq)was subsequently conducted to explore the underlying molecular mechanism,and Western blotting and coimmunoprecipitation were subsequently performed to validate the results.Animal studies were performed to evaluate the antitumor effects in vivo.Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC.Results Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells,resulting in cell cycle arrest.Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin.Notably,Apcin treatment led to the upregulation of the cell cycle regulator p21,which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells.In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth.Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue,and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval.Conclusion CDC20 is a novel molecular target in EC,and Apcin could be developed as a candidate antitumor drug for EC treatment.

Megestrol acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and early-stage endometrial adenocarcinoma: a prospective study

Objective To evaluate the efficacy of medroxyprogesterone acetate(MA)plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia(AEH)and early-stage grade 1 endometrial adenocarcinoma(G1 EAC)and the recurrence rate after treatment.Methods Sixty patients(aged 20-42 years)with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups(n=30)to receive oral MA treatment at the daily dose of 160 mg(control)or MA plus oral metformin(850 mg,twice a day)for at least 6 months.The treatment could extend to 12 months until a complete response(CR)was achieved,and follow-up hysteroscopy and curettage were performed every 3 months.For all the patients who achieved CR,endometrial expressions of IGFBP-rP1,p-Akt and p-AMPK were detected immunohistochemically.Results A total of 58 patients completed the treatment.After 9 months of treatment,23(76.7%)patients in the combined treatment group and 20(71.4%)in the control group achieved CR;two patients in the control group achieved CR after converting to the combined treatment.The recurrence rate did not differ significantly between the control group and combined treatment group(30.0%vs 22.7%,P>0.05).Ten(35.7%)patients in the control group experienced significant weight gain of 5.7±6.1 kg,while none of the patients receiving the combined treatment exhibited significant body weight changes.Compared with the control group,the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.Conclusion Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC,and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.

ZNF554 Inhibits Endometrial Cancer Progression via Regulating RBM5 and Inactivating WNT/β-Catenin Signaling Pathway

Objective:Uterine corpus endometrial carcinoma(UCEC),a kind of gynecologic malignancy,poses a significant risk to women’s health.The precise mechanism underlying the development of UCEC remains elusive.Zinc finger protein 554(ZNF554),a member of the Krüppel-associated box domain zinc finger protein superfamily,was reported to be dysregulated in various illnesses,including malignant tumors.This study aimed to examine the involvement of ZNF554 in the development of UCEC.Methods:The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay.Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection.CCK-8,wound healing,and Transwell invasion assays were employed to assess cell proliferation,migration,and invasion.Propidium iodide(PI)staining combined with fluorescence-activated cell sorting(FACS)flow cytometer was utilized to detect cell cycle distribution.qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels.Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5(RBM5).Results:The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines.Decreased expression of ZNF554 was associated with higher tumor stage,decreased overall survival,and reduced disease-free survival in UCEC.ZNF554 overexpression suppressed cell proliferation,migration,and invasion,while also inducing cell cycle arrest.In contrast,a decrease in ZNF554 expression resulted in the opposite effect.Mechanistically,ZNF554 transcriptionally regulated RBM5,leading to the deactivation of the Wingless(WNT)/β-catenin signaling pathway.Moreover,the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression onβ-catenin and p-glycogen synthase kinase-3β(p-GSK-3β).Similarly,the deliberate activation of RBM5 reduced the increase inβ-catenin and p-GSK-3βcaused by the suppression of ZNF554.In vitro experiments showed that ZNF554 overexpression-induced decreases in cell proliferation and migration were counteracted by RBM5 knockdown.Additionally,when RBM5 was overexpressed,it hindered the improvements in cell proliferation and migration caused by reducing the ZNF554 levels.Conclusion:ZNF554 functions as a tumor suppressor in UCEC.Furthermore,ZNF554 regulates UCEC progression through the RBM5/WNT/β-catenin signaling pathway.ZNF554 shows a promise as both a prognostic biomarker and a therapeutic target for UCEC.

Magnetic resonance imaging-based radiomics model for preoperative assessment of risk stratification in endometrial cancer

BACKGROUND Preoperative risk stratification is significant for the management of endometrial cancer(EC)patients.Radiomics based on magnetic resonance imaging(MRI)in combination with clinical features may be useful to predict the risk grade of EC.AIM To construct machine learning models to predict preoperative risk stratification of patients with EC based on radiomics features extracted from MRI.METHODS The study comprised 112 EC patients.The participants were randomly separated into training and validation groups with a 7:3 ratio.Logistic regression analysis was applied to uncover independent clinical predictors.These predictors were then used to create a clinical nomogram.Extracted radiomics features from the T2-weighted imaging and diffusion weighted imaging sequences of MRI images,the Mann-Whitney U test,Pearson test,and least absolute shrinkage and selection operator analysis were employed to evaluate the relevant radiomic features,which were subsequently utilized to generate a radiomic signature.Seven machine learning strategies were used to construct radiomic models that relied on the screening features.The logistic regression method was used to construct a composite nomogram that incorporated both the radiomic signature and clinical independent risk indicators.RESULTS Having an accuracy of 0.82 along with an area under the curve(AUC)of 0.915[95%confidence interval(CI):0.806-0.986],the random forest method trained on radiomics characteristics performed better than expected.The predictive accuracy of radiomics prediction models surpassed that of both the clinical nomogram(AUC:0.75,95%CI:0.611-0.899)and the combined nomogram(AUC:0.869,95%CI:0.702-0.986)that integrated clinical parameters and radiomic signature.CONCLUSION The MRI-based radiomics model may be an effective tool for preoperative risk grade prediction in EC patients.

Decoding exercise-induced atomic components and prognostic shifts in endometrial carcinoma through differentially expressed genes

Background:This study aimed to portray the atomic intelligence and prognostic implications of differentially expressed genes and their involvement in biological pathways in endometrial carcinoma,with a specific focus on the impacts of exercise on cancer.Methods:We utilized a multi-faceted approach,including volcano plots,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses,Venn diagrams,protein-protein interaction networks,Kaplan-Meier survival analysis,Gene Set Variety Analysis,and single-cell transcriptomic analysis.Furthermore,we profiled tumor mutational scenes,assessed the prognostic value of immune-related features,and conducted a comprehensive examination of genetic variations and their impact on tumor mutational burden across different cancer types.Multidimensional genomic interactions and methylation elements were also investigated.Using real-time quantitative PCR and immunofluorescence staining,the effects of B-cell lymphoma 2(BCL2)silencing on TNF-αand caspase-3 gene expression were evaluated.Results:Our study identified a noteworthy number of differentially expressed genes in endometrial carcinoma with potential links to athletic performance traits.BCL2 expression levels were found to be associated with survival outcomes,and its changeability across cancers was related to immune cell infiltration and immune checkpoint gene expression.Single-cell investigations uncovered cellular complexity within tumor microenvironments and critical biological pathways in BCL2-overexpressing cells.The expression flow and mutational effect of BCL2 in endometrial carcinoma were characterized,and the prognostic implications of immune-related features were assessed.Hereditary variations,including copy number variations and their relationship with gene expression and tumor mutational burden,were investigated.Multidimensional genomic transaction highlighted the essential role of regulatory genes in cancer pathogenesis.Silencing of the BCL2 gene significantly inhibited the proliferation of HEC-108 cells and promoted apoptosis,as evidenced by decreased TNF-αgene expression and increased caspase-3 gene expression.Immunofluorescence staining further confirmed these results.Conclusion:This study gives a point-by-point understanding of the atomic intelligence and prognostic implications in endometrial carcinoma and across various other cancers.BCL2’s role as a modulatory factor within the tumor-resistant environment and its potential impact on disease prognosis and response to immunotherapy were underscored.The multidimensional genomic analysis provides insights into the complex interaction between genetic and epigenetic variables in cancer,which may shed light on future therapeutic strategies.This study indicates that silencing the BCL2 gene can significantly inhibit tumor cell proliferation and promote apoptosis through the regulation of the TNF-αand caspase-3 pathways.

Development and validation of a circulating tumor DNA-based optimization-prediction model for short-term postoperative recurrence of endometrial cancer

BACKGROUND Endometrial cancer(EC)is a common gynecological malignancy that typically requires prompt surgical intervention;however,the advantage of surgical management is limited by the high postoperative recurrence rates and adverse outcomes.Previous studies have highlighted the prognostic potential of circulating tumor DNA(ctDNA)monitoring for minimal residual disease in patients with EC.AIM To develop and validate an optimized ctDNA-based model for predicting shortterm postoperative EC recurrence.METHODS We retrospectively analyzed 294 EC patients treated surgically from 2015-2019 to devise a short-term recurrence prediction model,which was validated on 143 EC patients operated between 2020 and 2021.Prognostic factors were identified using univariate Cox,Lasso,and multivariate Cox regressions.A nomogram was created to predict the 1,1.5,and 2-year recurrence-free survival(RFS).Model performance was assessed via receiver operating characteristic(ROC),calibration,and decision curve analyses(DCA),leading to a recurrence risk stratification system.RESULTS Based on the regression analysis and the nomogram created,patients with postoperative ctDNA-negativity,postoperative carcinoembryonic antigen 125(CA125)levels of<19 U/mL,and grade G1 tumors had improved RFS after surgery.The nomogram’s efficacy for recurrence prediction was confirmed through ROC analysis,calibration curves,and DCA methods,highlighting its high accuracy and clinical utility.Furthermore,using the nomogram,the patients were successfully classified into three risk subgroups.CONCLUSION The nomogram accurately predicted RFS after EC surgery at 1,1.5,and 2 years.This model will help clinicians personalize treatments,stratify risks,and enhance clinical outcomes for patients with EC.

Endometrial carcinoma with cervical stromal invasion:Three case reports

BACKGROUND Endometrial cancer is a kind of well-known tumors of female genitourinary system.Cervical stromal invasion is an adverse factor for poor prognosis of endometrial cancer.There is still controversy regarding the use of magnetic resonance imaging(MRI)in the diagnosis of cervical stromal invasion of endometrial cancer.The diagnosis of cervical stromal invasion varies significantly between different observers and institutions.We present a limited case series of the particular pattern of endometrial cancer,which infiltrates the cervical stroma and is often overlooked.CASE SUMMARY We present three cases of endometrial carcinoma with cervical stromal invasion with cancer-free uterine cavity.One patient,a reproductive-aged woman,exhibited irregular menstruation and was diagnosed with endometrial polyps by hysteroscopy and segmental curettage.A MRI scan revealed polypoid nodules within the internal cervical orifice.The other two cases were postmenopausal women who presented with abnormal vaginal bleeding.Hysteroscopy and segmental curettage suggested atypical hyperplasia of the endometrium.MRI scans did not detect any malignant signs in the endometrium.In one case,a nonthickened endometrium was observed,while in another,hyperplasia of the endometrium was seen.Notably,none of these patients had malignant tumors identified in the uterine cavity via MRI scans.However,postoperative pathological results following hysterectomy consistently indicated cervical stromal invasion.CONCLUSION Cervical stromal invasion is easily missed if no cancer is found in the uterine body on MRI.Immunohistochemistry of endoscopic curettage specimens should be conducted to avoid underestimation of the disease.

Effects of miR-214-5p and miR-21-5p in hypoxic endometrial epithelial-cell-derived exosomes on human umbilical cord mesenchymal stem cells

BACKGROUND Thin endometrium seriously affects endometrial receptivity,resulting in a significant reduction in embryo implantation,and clinical pregnancy and live birth rates,and there is no gold standard for treatment.The main pathophysiological characteristics of thin endometrium are increased uterine arterial blood flow resistance,angiodysplasia,slow growth of the glandular epithelium,and low expression of vascular endothelial growth factor,resulting in endometrial epithelial cell(EEC)hypoxia and endometrial tissue aplasia.Human umbilical cord mesenchymal stem cells(HucMSCs)promote repair and regeneration of damaged endometrium by secreting microRNA(miRNA)-carrying exosomes.However,the initiation mechanism of HucMSCs to repair thin endometrium has not yet been clarified.AIM To determine the role of hypoxic-EEC-derived exosomes in function of HucMSCs and explore the potential mechanism.METHODS Exosomes were isolated from normal EECs(EEC-exs)and hypoxia-damaged EECs(EECD-exs),before characterization using Western blotting,nanoparticletracking analysis,and transmission electron microscopy.HucMSCs were cocultured with EEC-exs or EECD-exs and differentially expressed miRNAs were determined using sequencing.MiR-21-5p or miR-214-5p inhibitors or miR-21-3p or miR-214-5p mimics were transfected into HucMSCs and treated with a signal transducer and activator of transcription 3(STAT3)activator or STAT3 inhibitor.HucMSC migration was assessed by Transwell and wound healing assays.Differentiation of HucMSCs into EECs was assessed by detecting markers of stromal lineage(Vimentin and CD13)and epithelial cell lineage(CK19 and CD9)using Western blotting and immunofluorescence.The binding of the miRNAs to potential targets was validated by dual-luciferase reporter assay.RESULTS MiR-21-5p and miR-214-5p were lowly expressed in EECD-ex-pretreated HucMSCs.MiR-214-5p and miR-21-5p inhibitors facilitated the migratory and differentiative potentials of HucMSCs.MiR-21-5p and miR-214-5p targeted STAT3 and protein inhibitor of activated STAT3,respectively,and negatively regulated phospho-STAT3.MiR-21-5p-and miR-214-5p-inhibitor-induced promotive effects on HucMSC function were reversed by STAT3 inhibition.MiR-21-5p and miR-214-5p overexpression repressed HucMSC migration and differentiation,while STAT3 activation reversed these effects.CONCLUSION Low expression of miR-21-5p/miR-214-5p in hypoxic-EEC-derived exosomes promotes migration and differentiation of HucMSCs into EECs via STAT3 signaling.Exosomal miR-214-5p/miR-21-5p may function as valuable targets for thin endometrium.

GENISTEIN INHIBITS PROLIFERATION OF HUMAN ENDOMETRIAL ENDOTHELIAL CELL IN VITRO

Objective To explore the effect of genistein on proliferation of human endometrial endothelial cells （HEECs） and glandular epithelium. Methods In vitro HEECs and human endometrial cancer-1B cell （HEC-1B ） were cultured with 0, 1, 10, 50, 100, and 200 μmol/L of genistein alone or indicated concentrations of genistein combined with 0.2 or 1 nmol/L 17β- estradiol （ 17β-E2）. Cell proliferation was determined by [ 3H ] -thymidine incorporation and cell cycle was measured by flow cytometry. Results After 96 hours of treatment, genistein inhibited the proliferation of HEECs in a dose-dependent manner. The stimulation index reduced from 100% （ without genistein treatment ） to about 1% （ 200 μmol/L genistein ）. HEECs were arrested at G1/0 and G2/M phase when treated with genistein for 96 hours. When the concentration of genistein was 200 μmol/L, the percentages of HEECs at G1/0, G2/M, and S phase were 96. 0%, 2.1%, and 1.9%, respectively. However, when HEECs were treated without genistein, the percentages of HEECs at G1/0, G2/M, and S phase were 76. 7%, 8.5%, and 14. 7%, respectively. 1713-E2 could not influence the effects of genistein on the proliferation of HEECs. Meanwhile, genistein could suppress the proliferation of HEC-1B. If the stimulation index of HEC-IB was defined as 100% when HEC-1B was treated with different doses of 1713-E2 （without genistein）, it was 67%, 19%, as well as 32% when cell was supplemented with 200 μmol/L genistein combined with 0, 0. 2, or 1 nmol/L 17β-E2, respectively. Conclusion Genistein at the concentration of 200 μmol/L can sufficiently inhibit the proliferation of HEECs and endometrial glandular epithelium simultaneously in vitro.

Fertility-sparing surgeries without adjuvant therapy through term pregnancies in a patient with low-grade endometrial stromal sarcoma:A case report

BACKGROUND Low-grade endometrial stromal sarcoma(LGESS)is a rare indolent tumor with a favorable prognosis.With the importance of improving quality of life recognized,fertility-sparing surgery may be an option for those young women.However,most of the reports suggested that stage IA patients might be candidates for fertility-sparing surgery,and adjuvant hormonal treatment was considered a feasible adjuvant therapy for reducing the recurrence risk of patients with LGESS and hysterectomy was recommended after the completion of pregnancy and delivery.CASE SUMMARY A 28-year-old pregnant woman diagnosed with stage IB LGESS was treated by fertility-sparing surgery when term cesarean section delivery was performed.Without any adjuvant treatment,she had the other successful term pregnancy and cesarean section 45 mo after first fertility-sparing surgery.Moreover,only hysteroscopic resection was performed to retain fertility again even when the tumor recurred after 6 years.So far the patient’s fertility and disease-free status have remained for more than 8 years without any adjuvant therapy despite local resection of the sarcoma.And the two babies were in good health.CONCLUSION For young patients with stage I LGESS,it seems that repeated fertility-sparing surgeries could be performed even after two term deliveries and the tumor recurrence,and it might be attempted without adjuvant therapy but the counseling should be considered as mandatory.

Value of Intrauterine Autologous Platelet-Rich Plasma Therapy on Endometrial Receptivity:A Literature Review

Endometrial receptivity is an important factor that influences embryo implantation.Thus,it is important to identify an applicable approach to improve endometrial receptivity in women undergoing assisted reproductive technology.Recently,growing evidence has indicated that intrauterine platelet-rich plasma(PRP)infusion is an effective method to obtain a satisfactory reproductive outcome by increasing endometrial thickness and improving endometrial receptivity.Therefore,the present review aims to outline the possible mechanisms of PRP on endometrial receptivity and summarize the present literature on the effects of PRP therapy in improving endometrial receptivity.

Effect of Estrogen and Antiestrogen on Chemotherapeutic Sensitivity of Endometrial Carcinoma Cell Line

Objective: To study the effect of estrogen and tamoxifen on chemotherapeutic sensitivity in ER(+) endometrial carcinoma cells.Methods: DNA fragmentation as the criteria for apoptotic cell death was used to evaluate the value of estrogen, tamoxifen and adriamycin in ER(+) endometrial carcinoma cells. DNA fragmentation was measured with the cell death ELISA.Results: Adriamycin and tamoxifen could induce apoptosis in ER(+) endometrial carcinoma cell. The cell apoptosis level was decreased with the increasing of 17-β-estradiol concentration (P<0.001) and was inversely proportional to 17-β-estradiol concentration (IgM) (P<0.01). The cell apoptosis level was increased with the increasing of tamoxifen concentration (P<0.01) and was also directly proportional to tamoxifen concentration (IgM). Furthermore, the cell apoptosis level was increased significantly after treated with both tamoxifen and adriamycin.Conclusion: Estrogen may block apoptosis induced by adriamycin in ER(+) endometrial carcinoma cell. Tamoxifen can increase the sensitivity of endometrial carcinoma cell to adriamycin. Tamoxifen combined with chemotherapeutic drug may be of significant therapeutic benefit in ER(+) endometrial carcinoma. Key words endometrial carcinoma - estrogen - tamoxifen - adriamycin - cell apoptosis

Assessment of Uterine Receptivity by Endometrial and Subendometrial Blood Flows Measured by Vaginal Color Doppler Ultrasound in Women Undergoing IVF Treatment

Objective To evaluate endometrial and subendometrial blood flows measured by vaginal color Doppler ultrasound as a predicator of endometrial receptivity in women undergoing IVF treatment. Methods A total of 119 infertile patients undergoing the first IVF/ICSI-ET cycle were recruited. Three groups were divided according to a color Doppler ultrasound examination performed on the day of hCG injection. Group A, endometrial and subendometrial blood flows were 2 branches and below; group B, endometrial and subendometrial blood flows were between 3 and 4 branches; group C, endometrial and subendometrial blood flows were 5 branches and above. Patients were transferred 1-3 embryos each. Demographic data, ovarian responses, endometrial thickness, PI, RI, development of embryo and IVF result among groups were compared. Results Demographic data, ovarian responses, endometrial thickness, PI, RI and development of embryo among groups have no significant difference. The pregnancy rate of group A was significantly lower than that of group B （P〈0.05） and group C （P〈0.01）. The implantation rate of group A was significantly lower than than of group C （P〈0.01）. There was no significant difference of the rate of pregnancy and implantation between group B and group C （P〉0.05）. Conclusion Endometrial and subendometrial blood flows measured by vaginal color Doppler ultrasound is a good predicator of pregnancy during IVF treatment. A good endometrial and subendometrial blood flows is benefit for the result of IVF.

Correlation between Depth of Myometrial Invasion and Degree of Lymph Node Affection in Cases of Endometrial Cancer

Introduction: Endometrial cancer is the fourth most frequent cancer in females. Many factors can affect prognosis of this type of cancer, these mainly are the degree of myometrial invasion by the tumour, pelvic and paraaortic lymph node spread as well as the tumour histological type (endometrioid vs non-endometrioid type). transvaginal ultrasound (TVS) is a highly accurate and easy method for preoperative evaluation of myometrial invasion. Aim of the Work: The aim of this work is to assess if there is relation between the depth of myometrial invasion by the tumor and the rate of lymph node involvement in cases of endometrial cancer. Results: It was found that there was a significant relation between lymph node affection and the depth of myometrial invasion, all the positive lymph node affections cases had myomterial invasion > 50.0%. Conclusion: The incidence of pelvic lymph node affection is very high in cases where the myometrium is deeply infiltrated with the tumor. Assessment of myometrial invasion preoperatively by TVU and microscopically by pathological examination of the myometrium after hysterectomy provides an accurate estimation of the rate of pelvic lymph node affection and hence necessitates lymphadenectomy procedures in cases where myometrium is deeply infiltrated by the tumor and omitted in cases where it is tumor free.

Vascular markers CD31,CD34,actin,VEGFB,and VEGFR2,are prognostic markers for malignant development in benign endometrial polyps

Intention of the study: The prevalence of endometrial polyps has been demonstrated in between 10% and 35% of all women, but knowledge regarding malignant potential within polyps is limited. Even though premalignant and malignant changes have been reported in up to 24% of all cases, no objective tissue markers have ever been developed for routine diagnostics to select high risk cases. As vascular changes and activation of endometrial angiogenesis has been demonstrated in former studies, our main objective was to evaluate different members of the angiogenic pathway as potential risk factors for cancer development. Patients and methods: Formalin-fixed, paraffin-embedded tissue from 15 women with benign endometrial polyps, and 16 women diagnosed with endometrial cancer were included. Immunohistochemical investigation with antibodies against VEGF, VEGF-B, VEGFR2, VEGFR3, CD31, CD34, actin, and factorVIII was performed, followed by evaluation of staining intensity of microvessels, evaluation of H-score in glands (cell membrane, cytoplasm) and stroma, and measurement of micro vessel density. Results: Expression of CD31 in microvessels was significantly stronger in cancers compared to endometrial polyps (P = 0.006 for arterioles, P = 0.038, for venyles, and P = 0.002 for capillaries, respectively), whereas, a reverse change was shown for CD34. Expression of actin in capillary walls was also significantly increased in cancers compared to polyps (P = 0.002). No significant difference was found for staining intensity in microvessels (arterioles, venyles or capillaries) in endometrial benign polyps compared with endometrial cancers for VEGF, VEGFB, VEGFR2, VEGFR3, or Factor VIII. Also no difference in H-score values between benign polyps and endometrial cancers could be detected in glandular epithelium, in epithelial cell membrane or in stroma for VEGFR3, CD31 or Factor VIII. Conclusions: The present study strongly indicates that activation of angiogenesis differs in benign endometrial polyps and endometrial cancers. Thus, immunohistochemical expression of specific angiogenic markers may be of great importance as prognostic factors in the routine diagnostics of this lesion. The ratio between stromal expression of CD34 and actin might be of particular interest to select polyps with increased malignant potential.

Immunocytochemical examination of PTEN and Ki-67 for endometrial carcinoma using thin-layer endometrial preparations

The current study is designed to evaluate certain immunocytochemical(ICC)biomarkers to gain a better cytodiagnosis.For this purpose,85 patients from March 2016 to March 2019 who planned to get a hysteroscopy assay were recruited.Cytological sampling was conducted by scratching the uterus cavity using SAP-1,and the samples were processed as liquid-based smears,using SurePath technology.36 patients diagnosed with EC or atypical endometrial hyperplasia were recruited in this study.33 cases were diagnosed with EC,and 3 cases were diagnosed with atypical endometrial hyperplasia,allocated with EC or precancerous lesions group.26 cases were diagnosed with benign lesions group.Among these cases,9 cases were diagnosed with endometrial simple hyperplasia,2 cases were diagnosed with complicated hyperplasia,5 cases were diagnosed with an irregular proliferation of endometrium and 10 cases were diagnosed with endometrial polyps.There were 23 cases in the healthy group.Staining in thin-layer endometrial preparations by ICC and using H-score or counting the percentage of stained cells.The presentation of PTEN in normal endometrium,benign lesions,and EC/precancerous lesions were different(p<0.01).Taking the cut-off value of 50(Youden’s index:0.698)PTEN expression for the diagnosis of EC/precancerous lesion,the sensitivity and specificity were 83.7%and 86.1%.The presentation of Ki-67 in normal endometrium,benign lesions,and EC/precancerous lesions were different(p<0.01).Taking the cut-off value of 15%(Youden’s index:0.76)Ki-67 expression for the diagnosis of EC/precancerous lesion,the sensitivity and specificity were 94.4%and 81.6%.In this study,the use of different cut-off values for Ki-67 and PTEN helped differentiate endometrial lesions.Immunocytochemistry in the ECT detection of PTEN and Ki-67 can improve the diagnostic capabilities of endometrial cancer and precancerous lesions.

LiNA OperaScope^(TM) for microwave endometrial ablation for endometrial polyps with heavy menstrual bleeding: A case report

BACKGROUND The procedure for microwave endometrial ablation(MEA)follows established MEA practice guidelines but requires hysteroscopic observation of the uterine lumen before and after MEA.When a luminal uterine lesion is recognized,its removal requires preoperative dilation of the cervix because the outer diameter of a conventional rigid hysteroscope is 8.7 mm.Recently,a fully disposable rigid hysteroscope(LiNA OperaScope^(TM))with a narrow diameter(4.4 mm)and forceps capable of extracting endometrial lesions has become available.CASE SUMMARY Here,we report a case of heavy menstrual bleeding(HMB)complicated by endometrial polyps where MEA was performed after removing endometrial polyps using the LiNA OperaScope^(TM) device.A 48-year-old woman with three prior pregnancies and three deliveries was referred to our hospital for further examination and treatment after being diagnosed with HMB 2 years earlier.The patient underwent MEA following endometrial polypectomy using LiNA OperaScope^(TM).After MEA,endometrial cauterization was again examined using the LiNA OperaScope^(TM),and the procedure was completed.No preoperative cervical dilation was performed.The patient’s clinical course was favorable,and she was discharged 3 h after surgery.One month after surgery,menstruation resumed,and both HMB and dysmenorrhea improved markedly from 10 preoperatively to 1 postoperatively,as assessed subjectively using the visual analog scale.The patient’s postoperative course was uneventful with no complic-ations.CONCLUSION LiNA OperaScope^(TM) can be a minimally invasive treatment for MEA of HMB with uterine lumen lesions.

Effect of Metformin on Endometrial Thickness and Subendometrial Flow Patterns in Anovulatory Patients with Polycystic Ovarian Syndrome

Background: Polycystic ovarian syndrome (PCOS) is considered the commonest endocrinological disorder affecting reproductive aged women. PCOS compromises fertility through various pathways. These pathways include hyperandrogenism, insulin resistance and impedance of the uterine and endometrial blood flow. Metformin improves the blood flow to the endometrium. It acts by reducing androgen level and correction of insulin resistance. Endometrial vascular indices were evaluated in this study to evaluate endometrial receptivity in anovulatory patients with PCOS. Aim of the Work: To evaluate the outcome of metformin administration in anovulatory patients with PCOS and its effect on the endometrium. This included its role in ovulation and improvement of pregnancy rates. Patients and Methods: This study included 85 patients from Ain Shams University outpatient infertility clinics from 1st of January, 2018 till 30th of June, 2018. We investigated these patients before treatment with ultrasound on day 14, 21. We evaluated endometrial thickness, uterine artery flow pattern, endometrial and subendometrial flow patterns. The patients received metformin 500 mg three times per day for three months. After this duration, we reevaluated them by ultrasound at days 14, 21. Results: Metformin therapy resulted in a significant increase of endometrial thickness and had a significant decrease on uterine, endometrial and subendometrial resistance index (R.I) and pulsatility index (P.I) at day 14, 21 compared to pre-treatment values indicating better blood flow. Conclusion: Metformin therapy resulted in improvement of endometrial flow patterns. Also, it resulted in increase in endometrial thickness and improvement of uterine artery flow.

Antidiastole Value of Three-dimensional Ultrasonography and Power Doppler between Uterine Parenchyma Lumps and Endometrial Cancer:A Retrospective Study

Sometimes endometrial polyps,submucosal myomas,and endometrial cancer show similar findings under ultrasonography.The aim of this study was to assess the antidiastole value of blood flow parameters using three-dimensional(3D)power Doppler ultrasonography angiography(PDA)between endometrial cancer and uterine parenchyma lumps.The data of the blood flow indices in 3D-PDA including the vascularization index(VI),flow index(FI),and vascularization flow index(VFI)in 40 patients with endometrial cancer and 41 patients with uterine parenchyma lumps(endometrial polyps and submucosal myomas)were retrospectively analysed and compared utilizing Virtual Organ Computer-aided AnaLysis(VOCAL)software.The results showed that all the blood flow parameters(VI,FI,VFI)were significantly higher in women with endometrial cancer than in those with uterine parenchyma lumps(P<0.001).The area under the curve of ROC of VI,FI,and VFI was 0.98,0.84,and 0.97,respectively.Thus,the best predictor of endometrial carcinoma was VI with a sensitivity of 97.0% and a specificity of 91.0%.The optimal cutoff value of VI was 4.06%.Our data demonstrated that all of the blood flow signal parameters(including VI,FI,and VFI)in 3D power Doppler ultrasonography had significant antidiastole values between endometrial cancer and uterine parenchyma lumps to assist clinicians in properly diagnosing patients.