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.

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.

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.

Synchronous endometrial and ovarian cancer: A case report

BACKGROUND Synchronous endometrial and ovarian cancer(SEOC)is a rare genital tract tumor.Precise diagnosis is crucial for the disease management since prognosis and overall survival differ substantially between metastatic endometrial cancer(EC)or OC.In this review we present 2 cases of women who were diagnosed with SEOC,and discuss the clinical characteristic of SEOC,diagnostic and molecular profiling issues.Next generation sequencing of 10 gene panel was performed on cancerous tissue and uterine lavage samples.CASE SUMMARY In our report patients with SEOC had endometroid type histology with early stage and low-grade histology for both EC and OC.They underwent surgical treatment and staging.Next-generation sequencing of 10 gene-panel identified CTNNB1,PIK3CA,and PTEN gene mutations in ovarian tissue in one case,while none of these genes were mutated in other case.Literature review in support to our data suggest a good prognosis for SEOC diagnosed at early stage.CONCLUSION Accurate diagnosis of SEOC is essential for disease management and gene mutation analysis can be helpful as a complementary diagnostic and prognostic tool.

Superiority of indocyanine green-enhanced near-infrared fluorescence-guided imaging for laparoscopic lymph node dissection in patients with early-stage endometrial cancer: A retrospective cohort study

Objective:Laparoscopic pelvic lymph node dissection(LPND),which is an effective therapy for endometrial cancer,is challenging because of the complexity of the procedure and the occurrence of postoperative complications.This study aimed to explore whether indocyanine green(ICG)-enhanced nearinfrared(NIR)fluorescence-guided LPND is superior to LPND in the context of early-stage endometrial carcinoma.Methods:In this retrospective study,we included the medical records of 190 patients with early-stage endometrioid adenocarcinoma who underwent LPND at the Department of Obstetrics and Gynecology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine between January 2019 and January 2021.Depending on whether ICG-enhanced NIR fluorescence guidance was used,the patients were assigned to the ICG group or non-ICG group.Patients were followed-up for one year after surgery.Data on demographic characteristics,pathological results,operative outcomes,and complications were collected and analyzed.Results:The baseline characteristics were comparable between the ICG group and non-ICG group,including age,BMI,pregnancy history,and preoperative hemoglobin.For surgical outcomes,the patients in ICG group had significantly lower intraoperative blood loss(50 mL vs.120 mL,p<0.001),less postoperative pelvic drainage time(4.14±1.44 d vs.5.70±1.89 d,p¼0.001),shorter duration of hospital stay(5.26±1.41 d vs.7.37±1.85 d,p¼0.003),higher number of positive pelvic lymph nodes(PLNs)(1 vs.0,p¼0.003),and more PLN-positive cases(16.0%vs.3.6%,p¼0.003)than the patients in non-ICG group.However,no significant differences were noted in blood transfusion requirement,operative time,hemoglobin level decreases,number of PLNs harvested,or the presence of lymphocysts between the two groups.Conclusion:Our study showed that ICG-enhanced NIR fluorescence-guided operation may improve the accuracy and safety of LPND.

Expression and function of long non-coding RNA DLX6-AS1 in endometrial cancer

Background:LncRNA DLX6-AS1 has been uncovered to exert effects on various cancers.Nevertheless,the impacts of DLX6-AS1 on endometrial cancer(EC)development remained obscure.The study explored the influence of DLX6-AS1 on EC progression via the microRNA(miR)-374a-3p/zinc-finger protein(ZFX)axis.Methods:EC cell lines were collected and DLX6-AS1,miR-374a-3p,and ZFX levels in EC cell lines were detected.The EC cells were transfected with DLX6-AS1,miR-374a-3p,and ZFX constructs to examine the biological functions of EC cells.The xenograft model was established for detecting tumor growth.Rescue experiments were conducted to verify the interaction of DLX6-AS1,miR-374a-3p,and ZFX in EC cells.Results:DLX6-AS1 and ZFX levels were elevated,while miR-374a-3p exhibited a reduced level in EC cells.Silencing DLX6-AS1 and elevated miR-374a-3p expressions repressed the biological activities of EC cells.Reduced DLX6-AS1 repressed tumor development.MiR-374a-3p silencing reversed the impacts of DLX6-AS1 silencing,while ZFX overexpression abrogated the impacts of miR-374a-3p elevation on EC cell growth.Mechanically,DLX6-AS1 was found to bind to miR-374a-3p,and miR-374a-3p targeted ZFX.Conclusion:DLX6-AS1 depletion restricts the malignant phenotype of EC cells.The study might provide novel therapeutic biomarkers for EC treatment.

Efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate COX regression analysis

BACKGROUND Endometrial cancer is one of the most commonly diagnosed gynecological cancers worldwide,and early-stage high-risk endometrial cancer has a poor prognosis.Adjuvant treatments after surgery,such as chemotherapy and radiotherapy,have been widely used in clinical practice to improve patient survival.Medroxyprogesterone acetate is a synthetic progestogen that has been reported to have potential anticancer effects in endometrial cancer.However,its efficacy,safety,and longterm prognostic benefits as an adjuvant treatment for endometrial cancer remain controversial.Therefore,this study aimed to observe the efficacy and prognostic impact of adjuvant medroxyprogesterone acetate treatment in patients with earlystage high-risk endometrial cancer and evaluate its safety.AIM To observe the efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate and to evaluate its safety.METHODS We collected the clinical data of 200 patients with early-stage high-risk endometrial cancer who were admitted to the Department of Obstetrics and Gynecology of our hospital from January 2018 to December 2022.The control group(100 patients)underwent conventional surgical treatment,and the study group(100 patients)was administered adjuvant medroxyprogesterone acetate tablets on top of the control group.The Kaplan-Meier curve analysis and log-rank test were performed to determine the possible factors influencing the 5-year cumulative survival rate in the patients.The Cox regression analysis was performed to identify the factors influencing the survival prognosis of endometrial cancer.RESULTS According to the Cox regression analysis,age[hazard ratio(HR)=4.636,95%confidence interval(95%CI):1.411-15.237],pathological type(HR=6.943,95%CI:2.299-20.977),molecular typing(HR=5.789,95%CI:3.305-10.141),and myometrial infiltration(HR=5.768,95%CI:1.898-17.520)were factors influencing the prognosis of patients with early-stage high-risk endometrial cancer.CONCLUSION Age,pathological type,molecular typing,and myometrial infiltration were all relevant factors affecting the prognosis of early-stage high-risk endometrial cancer.The potential long-term prognostic benefit of adjuvant postoperative radiotherapy in patients with early-stage high-risk endometrial cancer is worthy of clinical consideration.

MiR-200a and miR-200b target PTEN to regulate the endometrial cancer cell growth in vitro

Objective:To study whether miR-200a and miR-200b target PTEN gene expression to regulate the endometrial cancer cell growth in vitro. Methods:Endometrial cancer cells ECC-1 were cultured and transfected with the miR-200a and miR-200b mimics and inhibitors as well as the negative control mimics and inhibitors,and then the cell proliferation activity as well as the expression of PTEN and downstream genes in cells was determined; after transfection of miR-200a and miR-200b mimics as well as PTEN-3'UTR luciferase report gene plasmids,the fluorescence activity of luciferase reporter gene was determined. Results:12 h,24 h and 48 h after transfection,the cell proliferation activity of miR-200a mimics group and miR-200b mimics group were significantly higher than those of NC mimics group while the cell proliferation activity of mi R-200 a inhibitor group and miR-200b inhibitor group were significantly lower than those of NC inhibitor group; 48 h after transfection,PTEN expression in cells and PTEN-3'UTR luciferase reporter gene fluorescence activity of miR-200 a mimics group and miR-200b mimics group were significantly lower than those of NC mimics group while p-PI3K and p-Akt expression were significantly higher than those of NC mimics group; PTEN expression in cells and PTEN-3'UTR luciferase reporter gene fluorescence activity of miR-200 inhibitor group and miR-200b inhibitor group were significantly higher than those of NC inhibitor group while p-PI3K and p-Akt expression were significantly lower than those of NC inhibitor group. Conclusion:miR-200 a and miR-200b can promote the endometrial cancer cell growth in vitro by targeted inhibition of PTEN gene expression.

High-risk endometrial cancer may be benefit from adjuvant radiotherapy plus chemotherapy

Objective： To present patterns of practice and outcomes in the adjuvant treatment of intermediate- and high-risk endometrial cancer. Methods： Retrospective data on 224 women with intermediate-risk and high-risk endometrial cancer from 1999 to 2006 were reviewed. All patients underwent surgical staging. Patterns of adjuvant treatment, consisting of pelvic radiotherapy, chemotherapy, and radiotherapy plus chemotherapy, were assessed. The 3- and 5-year disease-specific survival （DSS） rates were calculated using the Kaplan-Meier method. Results： The difference in 5-year DSS rate was statistically significant between adjuvant group and non-adjuvant group （80.65% vs. 63.80%, P=0.040）. In 110 high-risk patients who underwent adjuvant treatment, both 5-year DSS rate and recurrent rate were significantly different in combined radiotherapy and chemotherapy group compared with radiotherapy alone and chemotherapy alone groups （DSS rate, P=0.049; recurrent rate, P=0.047）. In 83 intermediate-risk women who underwent adjuvant treatment, there was no significant difference in 5-year DSS rate and recurrence rate among the combined radiotherapy and chemotherapy, radiotherapy alone and chemotherapy alone groups （DSS rate, P=0.776; recurrent rate, P=0.937）.

Estrogen and insulin synergistically promote endometrial cancer progression via crosstalk between their receptor signaling pathways

Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed yet.Methods: Here, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth in vitro and in vivo, effects of estradiol and insulin on apoptosis and cell cycle distribution, and expression and activation of estrogen receptor(ER), insulin receptor(InsR), and key proteins in the PI3K and MAPK pathways were examined after combined stimulation with estradiol and insulin.Results: Compared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-β and IRS-1, whereas insulin significantly induced phosphorylation of ER-α. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-β inhibition had a limited effect on estradiol-dependent proliferation,cell cycle, and apoptosis, whereas ER-α inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in mice.Conclusions: Estrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-β and ER-α,promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways.

Leptin Activates STAT3 and ERK1/2 Pathways and Induces Endometrial Cancer Cell Proliferation

Obesity is an established risk factor for endometrial cancer.Leptin,a secreted protein of the ob gene by white adipose tissue,plays an important role in the regulation of food intake and energy consumption in the brain and acts as a potential growth stimulator in normal and neoplastic cancer cells.However,a direct role for leptin in endometrial cancer has not been demonstrated.In the present study,the effect of leptin on the proliferation of Ishikawa endometrial cancer cells was investigated as well as the possible mechanism（s） underlying this action in endometrial cancers which express both short and long isoforms of leptin receptors.The expression of leptin receptor（ObRb） in Ishikawa cells was detected by RT-PCR and Western blotting.The cells after serum starvation,were treated by leptin with various concentrations（0,10,50,100,150 ng/mL） for different durations（6,12,24 h）.The effect of leptin treatment on cell proliferation was examined by MTT assay.Meanwhile,inhibitory effect of Janus tyrosine kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3） inhibitor AG490 or extracellular signal-regulated kinase 1/2（ERK1/2） inhibitor PD98059 on the proliferation of Ishikawa cells induced by leptin was also studied.Ishikawa cells were treated with 100 ng/mL leptin for various periods（0,20,40,60 min）,and the levels of STAT3 phosphorylation and ERK1/2 phosphorylation were examined by Western blotting.The results showed that leptin induced the phosphorylation of STAT3 and the activation of ERK1/2 in a time-and dose-dependent manner in the Ishikawa endometrial cancer cells.Blocking STAT3 phosphorylation with the inhibitor AG490,or blocking ERK1/2 activation by the specific ERK1/2 kinase inhibitor,PD98059,abolished leptin-induced proliferation of Ishikawa cells.In addition,leptin was found to potently induce the invasion of endometrial cancer cells in a Matrigel invasion assay.Leptin-stimulated invasion was effectively blocked by pharmacological inhibitors of STAT3（AG490） and ERK1/2 kinase（PD98059）.These results suggested that leptin promotes endometrial cancer growth and invasiveness by activating STAT3 and ERK1/2 signaling pathways and therefore blocking its action at the receptor level can be a rational therapeutic strategy.

Proteiomic patterns for endometrial cancer using SELDI-TOF-MS

Serum samples from endometrial cancer (EC) patients and healthy females were analyzed using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to discover the potential diagnostic biomarker for detection of EC. A preliminary training set of spectra derived from 40 EC patients and 30 healthy women were used to develop a proteomic model that effectively discriminated cancer patients from healthy women. The training set had a specificity of 100% and sensitivity of 92.5% in the EC detection. A blind test set, including 20 new cancer cases and 10 healthy women, was used to validate the sensitivity and specificity of this multivariate model, which had a corresponding results of 60% in specificity and 75% in sensitivity, respectively. The combination of SELDI-TOF-MS with bioinformatics tools could help find new biomarkers and establish the detection of EC with high sensitivity and specificity.

Clinical significance and role of up-regulation of SERPINA3 expression in endometrial cancer

BACKGROUND Serpin peptidase inhibitor,clade A member 3(SERPINA3)belongs to the serpin family with an inhibitory activity against proteases.Its aberrant expression has been observed in a wide range of tumor cells.However,its clinical significance and biological function in endometrial cancer have been rarely studied.We designed a study to determine the levels of SERPINA3 and its significance in patients with endometrial cancer.AIM To investigate the clinical significance and role of SERPINA3 expression in endometrial cancer cells.METHODS Eighty endometrial tissue samples collected from patients with endometrial cancer were included in an observation group and 80 paraffin-embedded tissues samples collected from patients with normal endometrial tissues undergoing myomectomy were employed as a control group between January 2014 and December 2018.The expression of SERPINA3 mRNA was detected by quantitative polymerase chain reaction(PCR)for all endometrial tissues included in the study.RESULTS The positive expression rate of SERPINA3 protein in endometrial cancer cells was 71.25%in the observation group,which was significantly higher than that in the control group(31.25%;P<0.05).There was no correlation between SERPINA3 protein in endometrial cancer cells and the age range at which women experienced menopause(P>0.05).However,it was associated with pathological grade,clinical stage,vascular invasion,and lymph node metastasis(P<0.05).Pathological grade,clinical stage,vascular invasion,and lymph node metastasis were independent prognostic factors for endometrial cancer.CONCLUSION The follow-up study of SERPINA3 can be used as a prognostic biomarker for endometrial cancer and as one of the targets for bio-targeted therapy for endometrial cancer.

Preoperative markers for the prediction of high-risk features in endometrial cancer

BACKGROUND Preoperative evaluations aiming to assess high-risk features in clinical stage 1 endometrial cancer patients are crucial to refer these patients to gynecologic oncologists.Cancer antigen 125(CA125)and human epididymis protein 4(HE4)have been reported in endometrial cancer patients with poor prognostic factors.AIM To evaluate the association between preoperative levels of CA125 and HE4 and high-risk features and establish optimal cut-off values in clinical stage 1 endometrial cancer.METHODS A retrospective study was conducted in clinical stage 1 endometrial cancer patients who underwent primary surgery between January 2013 and December 2018.A total of 128 patients had preoperative serum CA125 and HE4 measurements.High-risk features included grade 3 tumors,large tumor sizes(more than 2 cm),deep myometrial invasion(more than 50%),lymphovascular space invasion(LVSI),cervical involvement,extrauterine involvement and node metastasis.Receiver operating characteristic(ROC)curves were generated to analyze the optimal cut-off values.RESULTS The mean age of the patients was 57.4 years,and 69.5%of them were postmenopausal.Most patients presented with stage I disease(67.2%)and had the endometrioid subtype(97.7%).The median CA125 and HE4 levels in all patients were 22.1 U/mL and 104.7 pmol/L,respectively.CA125 and HE4 levels were significantly elevated in those with large tumor sizes,deep myometrial invasion,LVSI,extrauterine metastasis,and advanced stage,but node metastasis was associated with elevated CA125 only.According to the ROC curve,both serum markers had statistical significance for the prediction of high-risk features only in postmenopausal patients,with an optimal cut-off value of 20 U/mL for CA125[area under the concentration-time curve(AUC)=0.72,P=0.002]and 113 pmol/L for HE4(AUC=0.70,P=0.006).The combination of both serum markers had 80%sensitivity and 64.4%positive predictive value.Significantly worse 5-year disease-free survival was observed in patients with high levels of CA125 and HE4(78.4%and 100%,respectively;P=0.01).CONCLUSION Preoperative CA125 levels greater than 20 U/mL or HE4 levels greater than 113 pmol/L are associated with an increased risk of having high-risk features and present as prognostic factors in clinical stage 1 postmenopausal endometrial cancer patients.This information is helpful for general gynecologists to refer high-risk patients to gynecologic oncologists to perform complete surgical staging.

Identification of novel Lynch syndrome mutations in Chinese patients with endometriod endometrial cancer

Objective:Lynch syndrome(LS)predisposes patients to early onset endometrioid endometrial cancer(EEC).However,little is known about LS-related EEC in the Chinese population.The aim of this study was to investigate the prevalence of LS and to identify the specific variants of LS in Chinese patients with EEC.Methods:We applied universal immunohistochemistry screening to detect the expression of mismatch repair(MMR)proteins,which was followed by MLH1 methylation analysis to identify suspected LS cases,next-generation sequencing(NGS)to confirm LS,and microsatellite instability(MSI)analysis to verify LS.Results:We collected 211 samples with EEC.Twenty-seven(27/211,12.8%)EEC cases had a loss of MMR protein expression.After MLH1 methylation analysis,16 EEC cases were suggested to be associated with LS.Finally,through NGS and MSI analysis,we determined that 10 EEC(10/209,4.78%)cases were associated with LS.Among those cases,3 unreported mutations(1 frameshift and 2 nonsense)were identified.M SH6 c.597_597delC,found in 4 patients,is likely to be a founder mutation in China.Conclusions:We demonstrated the feasibility of a process for LS screening in Chinese patients with EEC,by using universal immunohistochemistry screening followed by MLH1 methylation analysis and confirmation through NGS and MSI analysis.The novel mutations identified in this study expand knowledge of LS.

Red meat intake and the risk of endometrial cancer:Metaanalysis of observational studies

AIM:To evaluate whether red meat intake is related to the risk of endometrial cancer(EC) using meta-analysis.METHODS:We searched Pub Med,EMBASE,and the Cochrane Library up to June 2013,using common keywords related to red meat and EC.Case-control studies and cohort studies comparing the risk of endometrial cancer among categories by the amount of intake were included.Eleven case-control studies and five cohort studies met our criteria.We performed a conventional and a dose-response meta-analysis of case-control studies using the Der Simonian-Laird method for random-effects.For cohort studies we performed a conventional meta-analysis.Publication bias was evaluated using Egger's test.RESULTS:In the meta-analysis of 11 case-control studies including 5419 cases and 12654 controls,higher red meat consumption was associated with an increased risk of EC [summary relative risk(SRR) = 1.43,95%CI:1.15-1.79;I2 = 73.3% comparing extreme intake categories).In a dose-response analysis,for red meat intake of 100 g/d,SRR was 1.84(95%CI:1.64-2.05).In contrast,in the meta-analysis of five prospective studies including a total of 2549 cases among 247746 participants,no significant association between red meat intake and EC risk(SRR = 0.97,95%CI:0.85-1.11;I2 = 4.9% comparing extreme intake categories) was observed.CONCLUSION:Our meta-analysis found a significantlinear association between red meat intake and EC risk based on case-control studies but this was not confirmed in prospective studies.

Endometriosis-associated endometrioid adenocarcinoma of the fallopian tube synchronized with endometrial adenocarcinoma:A case report

BACKGROUND Endometriosis is a common gynecological disorder that affects women of reproductive age.It is characterized by a cancer-like invasion of the extra-uterine endometrium and exhibits a strong association with ovarian clear cell cancer and endometrioid cancer.Endometriosis-associated fallopian tube endometrioid adenocarcinoma synchronized with endometrial adenocarcinoma was rarely reported.CASE SUMMARY A 49-year-old woman was referred to our hospital complaining about abnormal vaginal bleeding for three years following unsatisfactory medication.Intraop-erative frozen sections unexpectedly unveiled an endometrioid cancer of the left fallopian tube with superficial invasion surrounded by diffuse endometriosis synchronized with endometrioid endometrial cancer.CONCLUSION It was difficult to make a differential diagnosis when confronted with incidental findings of fallopian tube cancer lesions synchronized with endometrial cancer.The key differential diagnosis of primary endometriosis-associated endometrioid adenocarcinoma of the fallopian tube from endometrial adenocarcinoma invol-vement relies on the pathological identification of malignant transformation in fallopian tube endometriosis disease.

Expressions of claudin-4 and claudin-1 in endometrial cancer and their significance

Objective:To observe the expressions of claudin-4 and claudin-1 in endometrial cancer and explore their correlations with clinicopathological parameters of endometrial cancer.Methods:Immunohistochemical methods(SP) were used to detect the expressions of claudin-4 and claudin-1 in 52 tissue samples of endometrial cancer,24 of atypical hyperplasia,20 of pericancerous endometrium,and 19 of endometrium at proliferative phase.And then the expressions were analyzed statistically to find out the correlations with clinicopathological parameters of endometrial cancer.Results:Positive rate of claudin-4 was 36.8%,70.8% and 90.4% in endometrium at proliferative phase,atypical hyperplasia and endometrial cancer,respectively,with significantly differences between them(P<0.05),and it was statistically different between pericancer endometrium and endometrial cancer(P<0.05).Positive rate of claudin-1 was 89.5%,66.7% and 63.5%,respectively showing a descending tendency and significantly differences between endometrium at proliferative phase and endometrial caner(P<0.05),and it was also statistically significantly different between pericancer endometrium and endometrial cancer(P<0.05).The high expression rate of claudin-4 was related to invasion depth,but not to histological grading,pathological staging or lymph node metastasis of endometrial cancer,and the low expression of claudin-1 in endometrial cancer was not associated with histological grading,pathological staging,invasion depth or lymph node metastasis.Conclusion:The expression levels of claudin-4 and claudin-1 are correlated with onset and development of endometrial cancer.

Metformin: A possible drug for treatment of endometrial cancer

Metformin is a widely used first-line drug for treatment of type 2 diabetes mellitus. In recent years, it has been reported that administration of metformin can reduce carcinogenic risk and inhibit proliferation of cancer cells including those from glioma and breast cancer. The underlying mechanism is thought to involve increased LKB-1 phosphorylation induced by metformin, followed by LKB-1 phosphorylation and activation of AMP-activated protein kinase (AMPK), which then inhibits the mammalian target of rapamycin (mTOR) pathway and results in inhibition of cell proliferation. In endometrial cancer, metformin causes cell cycle arrest in vitro, reduces hTERT mRNA, inhibits the mTOR pathway via AMPK, and is involved in inhibition of phosphorylation of S6 ribosomal protein (S6RP). Metformin promotes expression of progesterone receptor by an action opposite to that of insulin-like growth factor-2 (IGF-2) when used in combination with medroxyprogesterone acetate. This enhances the antitumor effect and this approach may be applicable in a clinical setting.

The Role of Chest Computed Tomography in the Work-up of Patients with Cervical or Endometrial Cancer

Background and Objectives: To determine whether chest CT-scan in patients with cervical or endometrial cancer is of additional value for planning initial treatment and work-up. Methods: A retrospective analysis was performed of 465 patients diagnosed with cervical or endometrial cancer between January 2003 and December 2007. All patients who underwent a chest CT-scan before treatment were included for analysis. Results: Out of 465 patients 74 patients underwent a pre-treatment chest CT-scan (cervical cancer, n = 58, and endometrial cancer, n = 26). Abnormalities were detected in 53.4% (31/58) and 73.1% (19/26) of patients with cervical and endometrial cancer, respectively. The majority of abnormalities were presumed to be benign, yet work-up was adjusted in 28.6% (13/58 and 11/26), and therapy was adjusted in 17.6% (6/58, and 7/26) of patients with cervical and endometrial cancer. Pulmonary metastasis were observed in 10.3% (6/58) and 24.1% (7/26) of patients with cervical cancer, and endometrial cancer, respectively. Most patients with pulmonary metastasis presented with extended disease based on clinical examination. Conclusions: Chest CT scans in patients with cervical and endometrial cancer frequently demonstrate abnormalities that are most likely benign, yet work-up is adjusted in a substantial number of cases. Therefore, chest CT-scan is only recommended for those patients with a clinical suspicion of extended disease.