Effect of Radiofrequency Endometrial Ablation on Dysmenorrhea.

PubMed

Wyatt, Sabrina N; Banahan, Taylor; Tang, Ying; Nadendla, Kavita; Szychowski, Jeff M; Jenkins, Todd R

To examine rates of dysmenorrhea after radiofrequency endometrial ablation in patients with and without known dysmenorrhea symptoms prior to the procedure in a diverse population. Retrospective cohort study (Canadian Task Force classification II-2). Academic gynecology practice. A total of 307 women underwent endometrial ablation between 2007 and 2013 at our institution. Patients who had preoperative and postoperative pain symptom assessments as well as a description of pain timing recorded were included in our analysis. Exclusion criteria were age <19 years and operative biopsy findings consistent with complex atypical hyperplasia. The difference in preoperative and postoperative rates of dysmenorrhea was evaluated. Demographic information and other outcome variables were used to evaluate factors associated with resolution of dysmenorrhea. A total of 307 patients who underwent radiofrequency endometrial ablation were identified. After exclusions, 296 charts were examined, and 144 patients met our enrollment criteria. The mean age of the study cohort was 45.4 ± 6.2 years; 57 patients (40%) were African American, 16 (11%) had a body mass index (BMI) > 40, and 41 (29%) were of normal weight. Preoperative dysmenorrhea was reported by 100 patients (69%); 48 of these patients (48%) experienced resolution of symptoms postoperatively. Only 3 of the 44 patients (7%) without preoperative dysmenorrhea reported new-onset dysmenorrhea postoperatively. Significantly fewer patients had dysmenorrhea after compared to before radiofrequency ablation (55 of 144 [38%] vs 100 of 144 [69%]; p < .001). Resolution of dysmenorrhea after ablation was associated with reduction in bleeding volume (p = .048) but not with a reduction in frequency of bleeding (p = .12). Approximately one-half of women who undergo radiofrequency endometrial ablation to treat heavy menstrual bleeding who also have preoperative dysmenorrhea exhibit documented pain resolution after the procedure. Resolution of dysmenorrhea is more likely if menstrual flow volume is decreased postprocedure. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Endometrial Ablation

MedlinePlus

... or lighter levels. If ablation does not control heavy bleeding, further treatment or surgery may be needed. ... ablation is used to treat many causes of heavy bleeding. In most cases, women with heavy bleeding ...

Levonorgestrel-Releasing Intrauterine System (52 mg) for Idiopathic Heavy Menstrual Bleeding: A Health Technology Assessment

PubMed Central

Schaink, Alexis; Chan, Brian; Higgins, Caroline

2016-01-01

Background Heavy menstrual bleeding affects as many as one in three women and has negative physical, economic, and psychosocial impacts including activity limitations and reduced quality of life. The goal of treatment is to make menstruation manageable, and options include medical therapy or surgery such as endometrial ablation or hysterectomy. This review examined the evidence of effectiveness and cost-effectiveness of the 52-mg levonorgestrel-releasing intrauterine system (LNG-IUS) as a treatment alternative for idiopathic heavy menstrual bleeding. Methods We conducted a systematic review of the clinical and economic evidence comparing LNG-IUS with usual medical therapy, endometrial ablation, or hysterectomy. Medline, EMBASE, Cochrane, and the Centres for Reviews and Dissemination were searched from inception to August 2015. The quality of the evidence was assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We also completed an economic evaluation to determine the cost-effectiveness and budget impact of the LNG-IUS compared with endometrial ablation and with hysterectomy. The economic evaluation was conducted from the perspective the Ontario Ministry of Health and Long-Term Care. Results Relevant systematic reviews (n = 18) returned from the literature search were used to identify eligible randomized controlled trials, and 16 trials were included. The LNG-IUS improved quality of life and reduced menstrual blood loss better than usual medical therapy. There was no evidence of a significant difference in these outcomes compared with the improvements offered by endometrial ablation or hysterectomy. Mild hormonal side effects were the most commonly reported. The quality of the evidence varied from very low to moderate across outcomes. Results from the economic evaluation showed the LNG-IUS was less costly (incremental saving of $372 per person) and more effective providing higher quality-adjusted life years (incremental value of 0.05) compared with endometrial ablation. Similarly, the LNG-IUS costs less (incremental saving of $3,138 per person) and yields higher quality-adjusted life-years (incremental value of 0.04) compared with hysterectomy. Publicly funding LNG-IUS as an alternative to endometrial ablation and hysterectomy would result in annual cost savings of $3 million to $9 million and $0.1 million to $23 million, respectively, over the first 5 years. Conclusions The 52-mg LNG-IUS is an effective and cost-effective treatment option for idiopathic heavy menstrual bleeding. It improves quality of life and menstrual blood loss, and is well tolerated compared with endometrial ablation, hysterectomy, or usual medical therapies. PMID:27990196

Microwave endometrial ablation versus thermal balloon endometrial ablation (MEATBall): 5-year follow up of a randomised controlled trial.

PubMed

Sambrook, A M; Elders, A; Cooper, K G

2014-05-01

To compare long-term outcomes following microwave endometrial ablation (MEA™) and thermal balloon ablation (TBall). Follow up of a prospective, double-blind randomised controlled trial at 5 years. A teaching hospital in the UK. A total of 320 women eligible for and requesting endometrial ablation. Eligible women were randomised in a 1:1 ratio to undergo MEA or Tball. Postal questionnaires were sent to participants at a minimum of 5 years postoperatively to determine satisfaction with outcome, menstrual status, bleeding scores and quality of life measurement. Subsequent surgery was ascertained from the women and the hospital operative database. The primary outcome measure was overall satisfaction with treatment. Secondary outcomes included evaluation of menstrual loss, change in quality of life scores and subsequent surgery. Of the women originally randomised 217/314 (69.1%) returned questionnaires. Nonresponders were assumed to be treatment failures for data analysis. The primary outcome of satisfaction was similar in both groups (58% for MEA™ versus 53% for TBall, difference 5%; 95% CI -6 to 16%). Amenorrhoea rates were high following both techniques (51% versus 45%, difference 6%; 95% CI -5 to 17%). There was no significant difference in the hysterectomy rates between the two arms (9% versus 7%, difference 2%; 95% CI -5 to 9%). At 5 years post-treatment there were no significant clinical differences in patient satisfaction, menstrual status, quality of life scores or hysterectomy rates between MEA™ and Thermachoice 3, thermal balloon ablation. © 2014 Royal College of Obstetricians and Gynaecologists.

Comparison of the levonorgestrel-releasing intrauterine system, hysterectomy, and endometrial ablation for heavy menstrual bleeding in a decision analysis model.

PubMed

Louie, Michelle; Spencer, Jennifer; Wheeler, Stephanie; Ellis, Victoria; Toubia, Tarek; Schiff, Lauren D; Siedhoff, Matthew T; Moulder, Janelle K

2017-11-01

A better understanding of the relative risks and benefits of common treatment options for abnormal uterine bleeding (AUB) can help providers and patients to make balanced, evidence-based decisions. To provide comparative estimates of clinical outcomes after placement of levonorgestrel-releasing intrauterine system (LNG-IUS), ablation, or hysterectomy for AUB. A PubMED search was done using combinations of search terms related to abnormal uterine bleeding, LNG-IUS, hysterectomy, endometrial ablation, cost-benefit analysis, cost-effectiveness, and quality-adjusted life years. Full articles published in 2006-2016 available in English comparing at least two treatment modalities of interest among women of reproductive age with AUB were included. A decision tree was generated to compare clinical outcomes in a hypothetical cohort of 100 000 premenopausal women with nonmalignant AUB. We evaluated complications, mortality, and treatment outcomes over a 5-year period, calculated cumulative quality-adjusted life years (QALYs), and conducted probabilistic sensitivity analysis. Levonorgestrel-releasing intrauterine system had the highest number of QALYs (406 920), followed by hysterectomy (403 466), non-resectoscopic ablation (399 244), and resectoscopic ablation (395 827). Ablation had more treatment failures and complications than LNG-IUS and hysterectomy. Findings were robust in probabilistic sensitivity analysis. Levonorgestrel-releasing intrauterine system and hysterectomy outperformed endometrial ablation for treatment of AUB. © 2017 International Federation of Gynecology and Obstetrics.

[Application of TB type thermal balloon endometrial ablation for the treatment of abnormal uterine bleeding].

PubMed

Wang, W; Zhai, Y; Zhang, Z H; Li, Y; Zhang, Z Y

2016-11-08

Objective: To investigate the clinical efficacy, safety and promotion value of TB type thermal balloon endometrial ablation in the treatment of abnormal uterine bleeding. Methods: Fourty three patients who had received TB type endometrial ablation system for treatment of abnormal uterine bleeding from January, 2015 to January, 2016 in theDepartment of gynecology, Beijing Chaoyang Hospital were enrolled in this study. The intra-operative and post-operative complications and improvement of abnormal uterine bleeding and dysmenorrhea were observed. Results: There were nointra-operative complication occurred, such as uterine perforation, massive hemorrhage or surrounding organ damage. At 6 months after operation, 32 patients developed amenorrhea, 6 developed menstrual spotting, 3 developed menstruation with a small volume and 1 had a normal menstruation. No menstruation with an increased volume occurred. The occurrence of amenorrhea was 76.19% and the response rate was 97.62%.At 6 months after operation, 1 case had no response, 2 cases had partial response and 11 cases had complete response among the 14 cases of pre-operative dysmenorrhea; only 3 cases still had anemia among the 23 cases of pre-operative anemia. Compared with before treatment, patients with dysmenorrhea and anemia both significantly reduced with a statistically significant difference( P <0.01). Conclusion: TB type thermal balloon endometrial ablation has a significant efficacy with high safety for the treatment of abnormal uterine bleeding, which could have clinical promotion practice.

Transendoscopic Nd:YAG ablation of cystic lesions in 27 large animals: 1986-1995

NASA Astrophysics Data System (ADS)

Tate, Lloyd P.

1997-05-01

Hospital medical surgery records and laser logs were examined to determine the population of large animals presented to the College of Veterinary Medicine treated by laser and conventional means for cystic lesions. Cystic lesions were most frequently found in 2 anatomical locations: endometrial cysts and upper respiratory cysts. The majority of endometrial cysts were considered to be acquired, whereas the most frequently encountered upper respiratory cysts were believed to be congenital due to the fact they were most frequently seen in young animals. Nine mares, totaling 42 endometrial cysts, were presented to the Veterinary Teaching Hospital (VTH), all of which had been treated by transendoscopic Nd:YAG laser ablation. Eighteen of the respiratory cysts in the same time period were presented to the VTH, of which 10 received conventional surgery and 8 were laser photoablated. Respiratory cysts treated by conventional surgery were generally found in locations inaccessible to visualization by transendoscopic technique, and thus required a surgical approach under general anesthesia. All mares with endometrial cysts were presented with a history of conception failure. After laser ablation, a majority of the mares were able to carry a foal to term and none represented with recurrence of endometrial cysts. Horses that presented with upper respiratory cysts also did not experience recurrence of cysts; although several horses, 1 treated by laser ablation and 4 treated by conventional surgery for frontal and/or maxillary sinus cysts, had transitory sinusitis. Transendoscopic Nd:YAG photoablation of cysts appears to be a very satisfactory means of treating this particular form of lesion in large animals with minimal complications and it can be performed with the animal in a standing position as an outpatient.

A gata2-dependent transcription network regulates uterine progesterone responsiveness and endometrial function

USDA-ARS?s Scientific Manuscript database

Altered progesterone responsiveness leads to female infertility and cancer, but underlying mechanisms remain unclear. Mice with uterine-specific ablation of GATA binding protein 2 (Gata2) are infertile, showing failures in embryo implantation, endometrial decidualization, and uninhibited estrogen si...

Hysteroscopic resection on virtual reality simulator: What do we measure?

PubMed

Panel, P; Neveu, M-E; Villain, C; Debras, F; Fernandez, H; Debras, E

2018-06-01

The objective was to compare results of two groups of population (novices and experts) on a virtual reality simulator of hysteroscopy resection for different metrics and for a multimetric score to assess its construct validity. Nineteen gynecologist who had at least 5 years of experience with hysteroscopy and self-evaluated their expertise at 4/5 or 5/5 were included as expert population. Twenty first-year gynecology residents in Paris were included as novice population. A standardized set of 4 hysteroscopy resection cases (polypectomy, myomectomy, roller ball endometrial ablation and septum resection) was performed on a virtual reality simulator (HystSim™) by the group of novices and experts. Results obtained on the simulator for overall score and for the parameters were compared by applying the Mann-Whitney test. Overall score of novices and experts were significantly different for three resection cases (polypectomy P<0.001, myomectomy P<0.001, roller ball endometrial ablation <0.001). The overall score was not different in the septum resection (P=0.456). For the four cases, the economy score (included cumulative path length, procedure time and camera alignment) were statistically different between novices and experts (polypectomy P<0.001, myomectomy P=0.001, roller ball endometrial ablation P<0.001, septum resection P<0.001). The overall score on HystSim™ was able to discriminate novices between experts on polypectomy, myomectomy and roller ball endometrial ablation cases but not on septum resection. The economy score was the more reliable to reflect the surgeon experience. It could be used to evaluate and to train students on hysteroscopic resection on a virtual reality simulator. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The Epidermal Growth Factor Receptor Critically Regulates Endometrial Function during Early Pregnancy

PubMed Central

Large, Michael J.; Wetendorf, Margeaux; Lanz, Rainer B.; Hartig, Sean M.; Creighton, Chad J.; Mancini, Michael A.; Kovanci, Ertug; Lee, Kuo-Fen; Threadgill, David W.; Lydon, John P.; Jeong, Jae-Wook; DeMayo, Francesco J.

2014-01-01

Infertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns. The spatiotemporal expression of growth factors indicates that they play an important role in pregnancy. The goal of this study is to define the role of the ERBB family of growth factor receptors in endometrial function. Using conditional ablation in mice and siRNA in primary human endometrial stromal cells, we identified the epidermal growth factor receptor (Egfr) to be critical for endometrial function during early pregnancy. While ablation of Her2 or Erbb3 led to only a modest reduction in litter size, mice lacking Egfr expression are severely subfertile. Pregnancy demise occurred shortly after blastocyst implantation due to defects in decidualization including decreased proliferation, cell survival, differentiation and target gene expression. To place Egfr in a genetic regulatory hierarchy, transcriptome analyses was used to compare the gene signatures from mice with conditional ablation of Egfr, wingless-related MMTV integration site 4 (Wnt4) or boneless morphogenic protein 2 (Bmp2); revealing that not only are Bmp2 and Wnt4 key downstream effectors of Egfr, but they also regulate distinct physiological functions. In primary human endometrial stromal cells, marker gene expression, a novel high content image-based approach and phosphokinase array analysis were used to demonstrate that EGFR is a critical regulator of human decidualization. Furthermore, inhibition of EGFR signaling intermediaries WNK1 and AKT1S1, members identified in the kinase array and previously unreported to play a role in the endometrium, also attenuate decidualization. These results demonstrate that EGFR plays an integral role in establishing the cellular context necessary for successful pregnancy via the activation of intricate signaling and transcriptional networks, thereby providing valuable insight into potential therapeutic targets. PMID:24945252

Nuclear Receptor Co-Regulator Krüppel-like Factor 9 in Human Endometrial Stromal Cell Differentiation

USDA-ARS?s Scientific Manuscript database

The biological actions of ligand-bound estrogen (E) and progesterone (P) receptors are dependent on coregulator partner proteins. We have identified Krüppel-like Factor 9 (KLF9) as important for E and P actions in endometrial cells. Ablation of KLF9 in mice resulted in subfertility due partly to alt...

Management of Abnormal Uterine Bleeding with Emphasis on Alternatives to Hysterectomy.

PubMed

Billow, Megan R; El-Nashar, Sherif A

2016-09-01

Abnormal uterine bleeding (AUB) is a common problem that negatively impacts a woman's health-related quality of life and activity. Initial medical treatment includes hormonal and nonhormonal medications. If bleeding persists and no structural abnormalities are present, a repeat trial of medical therapy, a levonorgestrel intrauterine system, or an endometrial ablation can be used dependent on future fertility wishes. The levonorgestrel intrauterine system and endometrial ablation are effective, less invasive, and safe alternatives to a hysterectomy in women with AUB. A hysterectomy is the definitive treatment of AUB irrespective of the suspected cause when alternative treatments fail. Future studies should focus on detection of predictors for treatment outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

MIG-6 negatively regulates STAT3 phosphorylation in uterine epithelial cells

PubMed Central

Yoo, Jung-Yoon; Yang, Woo Sub; Lee, Jae Hee; Kim, Byung Gak; Broaddus, Russell R.; Lim, Jeong M.; Kim, Tae Hoon; Jeong, Jae-Wook

2017-01-01

Endometrial cancer is the most common malignancy of the female genital tract. Progesterone (P4) has been used for several decades in endometrial cancer treatment, especially in women who wish to retain fertility. However, it is unpredictable which patients will respond to P4 treatment and which may have a P4 resistant cancer. Therefore, identifying the mechanism of P4 resistance is essential to improve the therapies for endometrial cancer. Mitogen-inducible gene 6 (Mig-6) is a critical mediator of progesterone receptor (PGR) action in the uterus. In order to study the function of Mig-6 in P4 resistance, we generated a mouse model in which we specifically ablated Mig-6 in uterine epithelial cells using Sprr2f-cre mice (Sprr2fcre+Mig-6f/f). Female mutant mice develop endometrial hyperplasia due to aberrant phosphorylation of STAT3 and proliferation of the endometrial epithelial cells. The results from our immunoprecipitation and cell culture experiments showed that MIG-6 inhibited phosphorylation of STAT3 via protein interactions. Our previous study showed P4 resistance in mice with Mig-6 ablation in Pgr positive cells (Pgrcre/+Mig-6f/f). However, Sprr2fcre+Mig-6f/f mice were P4 responsive. P4 treatment significantly decreased STAT3 phosphorylation and epithelial proliferation in the uterus of mutant mice. We showed that Mig-6 has an important function of tumor suppressor via inhibition of STAT3 phosphorylation in uterine epithelial cells and the anti-tumor effects of P4 are mediated by the endometrial stroma. This data helps to develop a new signaling pathway in the regulation of steroid hormones in the uterus, and to overcome P4 resistance in human reproductive diseases, such as endometrial cancer. PMID:28925396

Considerations for ex vivo thermal tissue testing exemplified using the fresh porcine longissimus muscle model for endometrial ablation

NASA Astrophysics Data System (ADS)

Fugett, James H.; Bennett, Haydon E.; Shrout, Joshua L.; Coad, James E.

2017-02-01

Expansions in minimally invasive medical devices and technologies with thermal mechanisms of action are continuing to advance the practice of medicine. These expansions have led to an increasing need for appropriate animal models to validate and quantify device performance. The planning of these studies should take into consideration a variety of parameters, including the appropriate animal model (test system - ex vivo or in vivo; species; tissue type), treatment conditions (test conditions), predicate device selection (as appropriate, control article), study timing (Day 0 acute to more than Day 90 chronic survival studies), and methods of tissue analysis (tissue dissection - staining methods). These considerations are discussed and illustrated using the fresh extirpated porcine longissimus muscle model for endometrial ablation.

Through thick and thin: a pictorial review of the endometrium.

PubMed

Caserta, Melanie P; Bolan, Candice; Clingan, M Jennings

2016-12-01

The purpose of this pictorial review is to describe the normal appearance of the endometrium and to provide radiologists with an overview of endometrial pathology utilizing case examples. The normal appearance of the endometrium varies by age, menstrual phase, and hormonal status with differing degrees of acceptable endometrial thickness. Endometrial pathology most often manifests as either focal or diffuse endometrial thickening, and patients frequently present with abnormal vaginal bleeding. Endovaginal ultrasound (US) is the first-line modality for imaging the endometrium. This article will discuss the endometrial measurements used to direct management and workup of symptomatic patients and will discuss when additional imaging may be appropriate. Three-dimensional US is complementary to two-dimensional ultrasound and can be used as a problem-solving technique. Saline-infused sonohysterogram is a useful adjunct to delineate and detect focal intracavitary abnormalities, such as polyps and submucosal fibroids. Magnetic resonance imaging is the preferred imaging modality for staging endometrial cancer because it best depicts the depth of myometrial invasion and cervical stromal involvement. Unique imaging features and complications of endometrial ablation will be introduced. At the completion of this article, the reader will understand the spectrum of normal endometrial findings and will understand the workup of common endometrial pathology.

Second-generation endometrial ablation technologies: the hot liquid balloons.

PubMed

Vilos, George A; Edris, Fawaz

2007-12-01

Hysteroscopic endometrial ablation (HEA) was introduced in the 1980s to treat menorrhagia. Its use required additional training, surgical expertise and specialized equipment to minimize emergent complications such as uterine perforations, thermal injuries and excessive fluid absorption. To overcome these difficulties and concerns, thermal balloon endometrial ablation (TBEA) was introduced in the 1990s. Four hot liquid balloons have been introduced into clinical practice. All systems consist of a catheter (4-10mm diameter), a silicone balloon and a control unit. Liquids used to inflate the balloons include internally heated dextrose in water (ThermaChoice, 87 degrees C), and externally heated glycine (Cavaterm, 78 degrees C), saline (Menotreat, 85 degrees ) and glycerine (Thermablate, 173 degrees C). All balloons require pressurization from 160 to 240 mmHg for treatment cycles of 2 to 10 minutes. Prior to TBEA, preoperative endometrial thinning, including suction curettage, is optional. Several RCTs and cohort studies indicate that the advantages of TBEA include portability, ease of use and short learning curve. In addition, small diameter catheters requiring minimal cervical dilatation (5-7 mm) and short duration of treatment cycles (2-8 min) allow treatment under minimal analgesia/anesthesia requirements in a clinic setting. Following TBEA serious adverse events, including thermal injuries to viscera have been experienced. To minimize such injuries some surgeons advocate the use of routine post-dilatation hysteroscopy and/or ultrasonography to confirm correct intrauterine placement of the balloon prior to initiating the treatment cycle. After 10 years of clinical practice, TBEA is thought to be the preferred first-line surgical treatment of menorrhagia in appropriately selected candidates. Economic modeling also suggested that TBEA may be more cost-effective than HEA.

Endometrial ablation

MedlinePlus

... tissue can be removed using: High frequency radio waves Laser energy Heated fluids Balloon therapy Freezing Electrical ... eds. Atlas of pelvic anatomy and gynecologic surgery . 4th ed. Philadelphia, PA: Elsevier; 2016:chap 110. Carlson ...

Short and medium term outcomes after rollerball endometrial ablation for menorrhagia.

PubMed

Fraser, I S; Angsuwathana, S; Mahmoud, F; Yezerski, S

1993-04-05

To review prospectively the intraoperative, short and medium term outcomes of patients treated by rollerball endometrial ablation during the learning curve for this relatively new procedure. Seventy-seven women with menorrhagia (71 with dysfunctional bleeding; six with additional small intramural myomas) underwent hysteroscopic rollerball endometrial ablation by coagulation diathermy during 1.5% glycine irrigation, after a two-month period of hormonal suppression. OPERATIVE AND SHORT-TERM EFFECTS: These were recorded at operation and six-week follow-up. No serious short-term complications were recorded. Objective measurement of intraoperative blood loss was always less than 20 mL. One woman experienced uterine perforation with a narrow cervical dilator which did not interfere with the ablation, and two patients had mild postoperative uterine infections. One patient experienced persistent postoperative pain. MEDIUM-TERM OUTCOME: This was recorded at each visit, or by telephone, and confirmed by questionnaire at one year. Twenty-five per cent achieved complete amenorrhoea, 29% staining only, 30% light periods, 10% "normal" or erratic periods and 6% were unchanged. Five patients underwent a second ablation, and three of these later underwent hysterectomy. Measured menstrual blood loss fell from 104 +/- 19 mL (mean +/- standard error of mean) to 1.7 +/- 1.1 mL at six months in 18 women. Other menstrual symptoms were also often dramatically reduced. Of those women with dysmenorrhoea, 33% were cured and 43% markedly improved; of those with midcycle pain, 28% were cured and 53% markedly improved; of those with significant premenstrual symptoms, 13% were cured, 47% markedly improved, 11% unchanged, and 6% were worse. This new procedure is a safe and effective treatment for menorrhagia caused by dysfunctional uterine bleeding, with impressive ancillary benefits for dysmenorrhoea, midcycle pain and premenstrual tension. It is often called minimally invasive surgery, but it must be recognised that it is not minor surgery.

[Management of menometrorrhagia in women with and without pregnancy intention: hierarchy of therapies].

PubMed

Roman, H; Loisel, C; Puscasiu, L; Sentilhes, L; Marpeau, L

2008-12-01

The first line of treatment recommended for women with idiopathic menorrhagia is pharmaceutical agents, i.e. levonorgestrel intra-uterine device, tranexamic acid, estroprogestatif pills, oral progestin and non-sterodial anti-inflammatory drugs. The second line of treatment is surgical, using endometrial curettage for women who desire pregnancy in the future. On the other hand, in women who no longer intend to get pregnant either endometrial ablation or hysterectomy can be used. The menorrhagia associated with endometrial polyps is treated through the hysteroscopic polypectomy, which result can be improved by the use of the levonorgestrel intra-uterine device or the endometrial ablation. The menorrhagia related to submucosal myomas is managed by hysteroscopic myomectomy, either as a first line of treatment or following the failure of the pharmaceutical management. The first line of treatment of interstitial myomas is represented by the medical management, followed by laparoscopic or abdominal myomectomy for women who still want to be pregnant, and by myomectomy or uterine arteries embolization for women who no longer desire pregnancy. Hysterectomy is the most efficient treatment of menorrhagia due to interstitial myomas, and may be proposed either as a third line of treatment for the myomectomy and embolization failures or as a second line of treatment for women who do not wish to conserve their uterus. Finally, the treatment for women with clinically or radiologically suspected adenomyosis is medical, followed by hysterectomy for women who desire no pregnancy.

Hysterosalpingography After Radiofrequency Endometrial Ablation and Hysteroscopic Sterilization as a Concomitant Procedure.

PubMed

Hopkins, Matthew R; Laughlin-Tommaso, Shannon K; Wall, Darci J; Breitkopf, Daniel M; Creedon, Douglas J; El-Nashar, Sherif A; Famuyide, Abimbola O

2015-09-01

To evaluate the accuracy of hysterosalpingography (HSG) in patients who underwent concomitant radiofrequency endometrial ablation and hysteroscopic sterilization. This historical cohort study was conducted at a midwestern academic medical center. A total of 186 women (94 with combined procedure and 92 with sterilization alone) were identified as having undergone intervention between January 1, 2003, and June 30, 2011. Two reviewers blinded to the surgical procedure interpreted the standard clinically indicated HSGs in each group. The primary outcome assessed was the inability to rely on the microinserts for contraception based on HSG interpretation using manufacturers' guidelines (unsatisfactory HSG). Position of the devices and occlusion of tubes were assessed on all 3-month and, when available, all 6-month repeat HSGs. At the 3-month HSG, 5 of 76 (6.6%, 95% confidence interval [CI] 2.2-14.7%) in the sterilization-only group had unsatisfactory HSG compared with 13 of 71 (18.3%, 95% CI 10.1-29.3%) in the combined group (P=.03). After accounting for the seven patients who underwent repeat HSG at 6 months, 3 of 76 (3.95%, 95% CI 0.8-11.1%) in the sterilization-only group had unsatisfactory HSG compared with 13 of 71 (18.31%, 95% CI 10.1-29.3%) in the combined group (P=.005). After completing all clinically indicated HSGs, patients who undergo concomitant radiofrequency endometrial ablation and hysteroscopic sterilization have an approximate fivefold increase (odds ratio 5.45, 95% CI 1.48-20.0) in the rate of unsatisfactory HSG for purposes of documenting tubal occlusion. II.

Economic Evaluation of Global Endometrial Ablation Versus Inpatient and Outpatient Hysterectomy for Treatment of Abnormal Uterine Bleeding: US Commercial and Medicaid Payer Perspectives.

PubMed

Miller, Jeffrey D; Bonafede, Machaon M; Cai, Qian; Pohlman, Scott K; Troeger, Kathleen A; Cholkeri-Singh, Aarathi

2018-03-01

Every year, abnormal uterine bleeding (AUB) exacts a heavy toll on women's health and leads to high costs for the US health care system. The literature shows that endometrial ablation results in fewer complications, shorter recovery and lower costs than more commonly performed hysterectomy procedures. The objective of this study was to model clinical-economic outcomes, budget impact, and cost-effectiveness of global endometrial ablation (GEA) versus outpatient hysterectomy (OPH) and inpatient hysterectomy (IPH) procedures. A decision tree, state-transition (semi-Markov) economic model was developed to simulate 3 hypothetical cohorts of women who received surgical treatment for AUB (GEA, OPH, and IPH) over 1, 2, and 3 years to evaluate clinical and economic outcomes for GEA vs. OPH and GEA vs. IPH. Two versions of the model were created to reflect both commercial health care payer and US Medicaid perspectives, and analyses were conducted for both payer types. Total health care costs in the first year after GEA were substantially lower compared with those for IPH and OPH. Budget impact analysis results showed that increasing GEA utilization yields total annual cost savings of about $906,000 for a million-member commercial health plan and about $152,000 in cost savings for a typical-sized state Medicaid plan with 1.4 million members. Cost-effectiveness analysis results for both perspectives showed GEA as economically dominant (conferring greater benefit at lower cost) over both OPH and IPH in the 1-year commercial scenario. This study demonstrates that, for some patients, GEA may prove to be a safe, uterus-sparing, cost-effective alternative to OPH and IPH for the surgical treatment of AUB.

Randomised trial comparing hysterectomy with endometrial ablation for dysfunctional uterine bleeding: psychiatric and psychosocial aspects.

PubMed Central

Alexander, D. A.; Naji, A. A.; Pinion, S. B.; Mollison, J.; Kitchener, H. C.; Parkin, D. E.; Abramovich, D. R.; Russell, I. T.

1996-01-01

OBJECTIVE: To compare in psychiatric and psychosocial terms the outcome of hysterectomy and endometrial ablation for the treatment of dysfunctional uterine bleeding. DESIGN: Prospective randomised controlled trial. SETTING--Obstetrics and gynaecology department of a large teaching hospital. SUBJECTS: 204 women with dysfunctional bleeding for whom hysterectomy would have been the preferred treatment were recruited over 24 months and randomly allocated to hysterectomy (99 women) or to hysteroscopic surgery (transcervical resection (52 women) or laser ablation (53 women). MAIN OUTCOME MEASURES: Mental state, martial relationship, psychosocial and sexual adjustment in assessments conducted before the operation and one month, six months, and 12 months later. RESULTS: Both treatments significantly reduced the anxiety and depression present before the operation, and there were no differences in mental health between the groups at 12 months. Hysterectomy did not lead to postoperative psychiatric illness. Sexual interest after the operation did not vary with treatment. Overall, 46 out of 185 (25%) women reported a loss sexual interest and 50 out of 185 (27%) reported increased sexual interest. Marital relationships were unaffected by surgery. Personality and duration of dysfunctional uterine bleeding played no significant part in determining outcome. CONCLUSIONS: Hysteroscopic surgery and hysterectomy have a similar effect on psychiatric and psychosocial outcomes. There is no evidence that hysterectomy leads to postoperative psychiatric illness. PMID:8611783

Loss of CDH1 and Pten accelerates cellular invasiveness and angiogenesis in the mouse uterus.

PubMed

Lindberg, Mallory E; Stodden, Genna R; King, Mandy L; MacLean, James A; Mann, Jordan L; DeMayo, Francesco J; Lydon, John P; Hayashi, Kanako

2013-07-01

E-cadherin (CDH1) is a cell adhesion molecule that coordinates key morphogenetic processes regulating cell growth, cell proliferation, and apoptosis. Loss of CDH1 is a trademark of the cellular event epithelial to mesenchymal transition, which increases the metastatic potential of malignant cells. PTEN is a tumor-suppressor gene commonly mutated in many human cancers, including endometrial cancer. In the mouse uterus, ablation of Pten induces epithelial hyperplasia, leading to endometrial carcinomas. However, loss of Pten alone does not affect longevity until around 5 mo. Similarly, conditional ablation of Cdh1 alone does not predispose mice to cancer. In this study, we characterized the impact of dual Cdh1 and Pten ablation (Cdh1(d/d) Pten(d/d)) in the mouse uterus. We observed that Cdh1(d/d) Pten(d/d) mice died at Postnatal Days 15-19 with massive blood loss. Their uteri were abnormally structured with curly horns, disorganized epithelial structure, and increased cell proliferation. Co-immunostaining of KRT8 and ACTA2 showed invasion of epithelial cells into the myometrium. Further, the uteri of Cdh1(d/d) Pten(d/d) mice had prevalent vascularization in both the endometrium and myometrium. We also observed reduced expression of estrogen and progesterone receptors, loss of cell adherens, and tight junction molecules (CTNNB1 and claudin), as well as activation of AKT in the uteri of Cdh1(d/d) Pten(d/d) mice. However, complex hyperplasia was not found in the uteri of Cdh1(d/d) Pten(d/d) mice. Collectively, these findings suggest that ablation of Pten with Cdh1 in the uterus accelerates cellular invasiveness and angiogenesis and causes early death.

Loss of Cdh1 and Pten Accelerates Cellular Invasiveness and Angiogenesis in the Mouse Uterus1

PubMed Central

Lindberg, Mallory E.; Stodden, Genna R.; King, Mandy L.; MacLean, James A.; Mann, Jordan L.; DeMayo, Francesco J.; Lydon, John P.; Hayashi, Kanako

2013-01-01

ABSTRACT E-cadherin (CDH1) is a cell adhesion molecule that coordinates key morphogenetic processes regulating cell growth, cell proliferation, and apoptosis. Loss of CDH1 is a trademark of the cellular event epithelial to mesenchymal transition, which increases the metastatic potential of malignant cells. PTEN is a tumor-suppressor gene commonly mutated in many human cancers, including endometrial cancer. In the mouse uterus, ablation of Pten induces epithelial hyperplasia, leading to endometrial carcinomas. However, loss of Pten alone does not affect longevity until around 5 mo. Similarly, conditional ablation of Cdh1 alone does not predispose mice to cancer. In this study, we characterized the impact of dual Cdh1 and Pten ablation (Cdh1d/d Ptend/d) in the mouse uterus. We observed that Cdh1d/d Ptend/d mice died at Postnatal Days 15–19 with massive blood loss. Their uteri were abnormally structured with curly horns, disorganized epithelial structure, and increased cell proliferation. Co-immunostaining of KRT8 and ACTA2 showed invasion of epithelial cells into the myometrium. Further, the uteri of Cdh1d/d Ptend/d mice had prevalent vascularization in both the endometrium and myometrium. We also observed reduced expression of estrogen and progesterone receptors, loss of cell adherens, and tight junction molecules (CTNNB1 and claudin), as well as activation of AKT in the uteri of Cdh1d/d Ptend/d mice. However, complex hyperplasia was not found in the uteri of Cdh1d/d Ptend/d mice. Collectively, these findings suggest that ablation of Pten with Cdh1 in the uterus accelerates cellular invasiveness and angiogenesis and causes early death. PMID:23740945

Control of intrauterine fluid pressure during operative hysteroscopy.

PubMed

Shirk, G J; Gimpelson, R J

1994-05-01

To evaluate the safety of a commonly used piston pump that controls the infusion pressure of low-viscosity fluids in a continuous-flow hysteroscopic system during operative hysteroscopy. Consecutive patients requiring operative hysteroscopy. Three hospital facilities in the Midwest. Sequential sample of 250 women who underwent operative hysteroscopy. Endometrial ablations, resection of submucosal or pedunculated uterine leiomyomata with or without endometrial ablation, polyp resections, metroplasty, and lysis of synechiae. The most serious complication of operative hysteroscopy is fluid overload due to intravasation into the patient's vascular system. Low-viscosity fluids were infused by the Zimmer Controlled Distention Irrigation System. The instrument uses a closed-feedback loop to monitor cavity pressure and automatically regulates the flow to maintain the set point pressure. It is designed to operate in a pressure range of 0 to 80 mm Hg and at flows in excess of 450 ml/minute. In 250 operative hysteroscopies no fluid complications occurred when intrauterine pressure was maintained below 80 mm Hg. No clinically significant differences in intravasation were seen in any type of operative hysteroscopy. This controlled mechanical pump system with exact intrauterine pressure measurement reduced many technical difficulties associated with low-viscosity media, and created a safe environment for the media's use in operative hysteroscopy.

Mig-6 regulates endometrial genes involved in cell cycle and progesterone signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoo, Jung-Yoon; Kim, Tae Hoon; Lee, Jae Hee

2015-07-10

Mitogen inducible gene 6 (Mig-6) is an important mediator of progesterone (P4) signaling to inhibit estrogen (E2) signaling in the uterus. Ablation of Mig-6 in the murine uterus leads to the development of endometrial hyperplasia and E2-induced endometrial cancer. To identify the molecular pathways regulated by Mig-6, we performed microarray analysis on the uterus of ovariectomized Mig-6{sup f/f} and PGR{sup cre/+}Mig-6{sup f/f} (Mig-6{sup d/d}) mice treated with vehicle or P4 for 6 h. The results revealed that 772 transcripts were significantly regulated in the Mig-6{sup d/d} uterus treated with vehicle as compared with Mig-6{sup f/f} mice. The pathway analysis showed thatmore » Mig-6 suppressed the expression of gene-related cell cycle regulation in the absence of ovarian steroid hormone. The epithelium of Mig-6{sup d/d} mice showed a significant increase in the number of proliferative cells compared to Mig-6{sup f/f} mice. This microarray analysis also revealed that 324 genes are regulated by P4 as well as Mig-6. Cited2, the developmentally important transcription factor, was identified as being regulated by the P4-Mig-6 axis. To determine the role of Cited2 in the uterus, we used the mice with Cited2 that were conditionally ablated in progesterone receptor-positive cells (PGR{sup cre/+}Cited2{sup f/f}; Cited2{sup d/d}). Ablation of Cited2 in the uterus resulted in a significant reduction in the ability of the uterus to undergo a hormonally induced decidual reaction. Identification and analysis of these responsive genes will help define the role of P4 as well as Mig-6 in regulating uterine biology. - Highlights: • We identify Mig-6- and P4-regulated uterine genes by microarray analysis. • Mig-6 suppresses cell cycle progression and epithelial cell proliferation in uterus. • We identify the Mig-6 dependent induced genes by P4. • Cited2 plays an important role for decidualization as a P4 and Mig-6 target gene.« less

Evaluation and management of abnormal uterine bleeding in premenopausal women.

PubMed

Sweet, Mary Gayle; Schmidt-Dalton, Tarin A; Weiss, Patrice M; Madsen, Keith P

2012-01-01

Up to 14 percent of women experience irregular or excessively heavy menstrual bleeding. This abnormal uterine bleeding generally can be divided into anovulatory and ovulatory patterns. Chronic anovulation can lead to irregular bleeding, prolonged unopposed estrogen stimulation of the endometrium, and increased risk of endometrial cancer. Causes include polycystic ovary syndrome, uncontrolled diabetes mellitus, thyroid dysfunction, hyperprolactinemia, and use of antipsychotics or antiepileptics. Women 35 years or older with recurrent anovulation, women younger than 35 years with risk factors for endometrial cancer, and women with excessive bleeding unresponsive to medical therapy should undergo endometrial biopsy. Treatment with combination oral contraceptives or progestins may regulate menstrual cycles. Histologic findings of hyperplasia without atypia may be treated with cyclic or continuous progestin. Women who have hyperplasia with atypia or adenocarcinoma should be referred to a gynecologist or gynecologic oncologist, respectively. Ovulatory abnormal uterine bleeding, or menorrhagia, may be caused by thyroid dysfunction, coagulation defects (most commonly von Willebrand disease), endometrial polyps, and submucosal fibroids. Transvaginal ultrasonography or saline infusion sonohysterography may be used to evaluate menorrhagia. The levonorgestrel-releasing intrauterine system is an effective treatment for menorrhagia. Oral progesterone for 21 days per month and nonsteroidal anti-inflammatory drugs are also effective. Tranexamic acid is approved by the U.S. Food and Drug Administration for the treatment of ovulatory bleeding, but is expensive. When clear structural causes are identified or medical management is ineffective, polypectomy, fibroidectomy, uterine artery embolization, and endometrial ablation may be considered. Hysterectomy is the most definitive treatment.

A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.

PubMed

Rubel, Cory A; Wu, San-Pin; Lin, Lin; Wang, Tianyuan; Lanz, Rainer B; Li, Xilong; Kommagani, Ramakrishna; Franco, Heather L; Camper, Sally A; Tong, Qiang; Jeong, Jae-Wook; Lydon, John P; DeMayo, Francesco J

2016-10-25

Altered progesterone responsiveness leads to female infertility and cancer, but underlying mechanisms remain unclear. Mice with uterine-specific ablation of GATA binding protein 2 (Gata2) are infertile, showing failures in embryo implantation, endometrial decidualization, and uninhibited estrogen signaling. Gata2 deficiency results in reduced progesterone receptor (PGR) expression and attenuated progesterone signaling, as evidenced by genome-wide expression profiling and chromatin immunoprecipitation. GATA2 not only occupies at and promotes expression of the Pgr gene but also regulates downstream progesterone responsive genes in conjunction with the PGR. Additionally, Gata2 knockout uteri exhibit abnormal luminal epithelia with ectopic TRP63 expressing squamous cells and a cancer-related molecular profile in a progesterone-independent manner. Lastly, we found a conserved GATA2-PGR regulatory network in both human and mice based on gene signature and path analyses using gene expression profiles of human endometrial tissues. In conclusion, uterine Gata2 regulates a key regulatory network of gene expression for progesterone signaling at the early pregnancy stage. Published by Elsevier Inc.

Loss of Cdh1 and Trp53 in the uterus induces chronic inflammation with modification of tumor microenvironment

PubMed Central

Stodden, Genna R.; Lindberg, Mallory E.; King, Mandy L.; Paquet, Marilène; MacLean, James A.; Mann, Jordan L.; DeMayo, Francesco J.; Lydon, John P.; Hayashi, Kanako

2015-01-01

Type II endometrial carcinomas are estrogen independent, poorly differentiated tumors that behave in an aggressive manner. Since TP53 mutation and CDH1 inactivation occur in 80% of human endometrial type II carcinomas, we hypothesized that mouse uteri lacking both Trp53 and Cdh1 would exhibit a phenotype indicative of neoplastic transformation. Mice with conditional ablation of Cdh1 and Trp53 (Cdh1d/dTrp53d/d) clearly demonstrate architectural features characteristic of type II endometrial carcinomas, including focal areas of papillary differentiation, protruding cytoplasm into the lumen (hobnailing) and severe nuclear atypia at 6-mo of age. Further, Cdh1d/dTrp53d/d tumors in 12-mo old mice were highly aggressive, and metastasized to nearby and distant organs within the peritoneal cavity, such as abdominal lymph nodes, mesentery and peri-intestinal adipose tissues, demonstrating that tumorigenesis in this model proceeds through the universally recognized morphologic intermediates associated with type II endometrial neoplasia. We also observed abundant cell proliferation and complex angiogenesis in the uteri of Cdh1d/dTrp53d/d mice. Our microarray analysis found that most of the genes differentially regulated in the uteri of Cdh1d/dTrp53d/d mice were involved in inflammatory responses. CD163 and Arg1, markers for tumor-associated macrophages, were also detected and increased in the uteri of Cdh1d/dTrp53d/d mice, suggesting that an inflammatory tumor microenvironment with immune cell recruitment is augmenting tumor development in Cdh1d/dTrp53d/d uteri. Further, inflammatory mediators secreted from CDH1 negative, TP53 mutant endometrial cancer cells induced normal macrophages to express inflammatory related genes through activation of NFκB signaling. These results indicate that absence of CDH1 and TP53 in endometrial cells initiates chronic inflammation, promotes tumor microenvironment development following the recruitment of macrophages, and promotes aggressive endometrial carcinomas. PMID:24998851

Cesarean scar defects: an underrecognized cause of abnormal uterine bleeding and other gynecologic complications.

PubMed

Tower, Amanda M; Frishman, Gary N

2013-01-01

The gynecologic sequelae due to deficient uterine scar healing after cesarean section are only recently being identified and described. These include conditions such as abnormal bleeding, pelvic pain, infertility, and cesarean scar ectopic pregnancy, as well as a potentially higher risk of complications and difficulties during gynecologic procedures such as uterine evacuation, hysterectomy, endometrial ablation, and insertion of an intrauterine device. The proposed mechanism of abnormal uterine bleeding is a pouch or "isthmocele" in the lower uterine segment that causes delayed menstrual bleeding. The prevalence of symptomatic or clinically relevant cesarean scar defects (CSDs) ranges from 19.4% to 88%. Possible risk factors for CSD include number of cesarean sections, uterine position, labor before cesarean section, and surgical technique used to close the uterine incision. There are no accepted guidelines for the diagnostic criteria of CSD. We propose that a CSD be defined on transvaginal ultrasound or saline infusion sonohysterography as a triangular hypoechoic defect in the myometrium at the site of the previous hysterotomy. We also propose a classification system to aid in standardized classification for future research. Surgical techniques for repair of CSD include laparoscopic excision, resectoscopic treatment, vaginal revision, and endometrial ablation. Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.

HEALTH: laparoscopic supracervical hysterectomy versus second-generation endometrial ablation for the treatment of heavy menstrual bleeding: study protocol for a randomised controlled trial.

PubMed

Cooper, Kevin; McCormack, Kirsty; Breeman, Suzanne; Wood, Jessica; Scott, Neil W; Clark, Justin; Hawe, Jed; Hawthorn, Robert; Phillips, Kevin; Hyde, Angela; McDonald, Alison; Forrest, Mark; Wileman, Samantha; Scotland, Graham; Norrie, John; Bhattacharya, Siladitya

2018-01-24

Heavy menstrual bleeding (HMB) is a common problem affecting approximately 1.5 million women in England and Wales with a major impact on their physical, emotional, social and material quality of life. It is the fourth most common reason why women attend gynaecology outpatient clinics and accounts for one-fifth of all gynaecology outpatient referrals. Initial treatment in primary care is medical - either by means of oral or injected medication or the levonorgestrel-intrauterine system (Mirena®). If medical treatment fails then surgical treatment can be offered, either endometrial ablation (EA), which destroys the lining of the cavity of the uterus (endometrium), or hysterectomy, i.e. surgical removal of the uterus. While effective, conventional hysterectomy is invasive and carries a risk of complications due to injury to other pelvic structures. The procedure can be simplified and complications minimised by undertaking a 'supracervical' hysterectomy where the cervix is left in situ and only the body of the uterus removed. Recent advances in endoscopic technologies have facilitated increased use of laparoscopic supracervical hysterectomy (LASH) which can be performed as a day-case procedure and is relatively easy for the surgeon to learn. HEALTH (Hysterectomy or Endometrial AbLation Trial for Heavy menstrual bleeding) aims to address the question 'Is LASH superior to second generation EA for the treatment of HMB in terms of clinical and cost effectiveness?' Women aged < 50 years, with HMB, in whom medical treatment has failed and who are eligible for EA will be considered for trial entry. We aim to recruit women from approximately 30 active secondary care centres in the UK NHS who carry out both surgical procedures. All women who consent will complete a diary of pain symptoms from day 1 to day 14 after surgery, postal questionnaires at six weeks and six months after surgery and 15 months post randomisation. Healthcare utilisation questions will also be completed at the six-week, six-month and 15-month time-points. Measuring the comparative effectiveness of LASH vs EA will provide the robust evidence required to determine whether the new technique should be adopted widely in the NHS. International Standard Randomised Controlled Trials, ISRCTN49013893 . Registered on 28 January 2014.

Using endometrial ablation as a treatment for abnormal bleeding: energy source comparisons and clinical results

NASA Astrophysics Data System (ADS)

Ryan, Thomas P.

2000-01-01

A great number of women suffer from abnormal uterine bleeding. Most do not want to undergo a hysterectomy and have searched for an alternative treatment. Ablation of the endometrium has become a viable alternative. Initially, surgical applications utilized thermal ablation by passing a rolling electrode, energized by monopolar radiofrequency (RF) energy, to ablate the inner uterine lining. This procedure was done under visual guidance and required practiced surgical skills to perform the ablation. It was not possible to assess subsurface damage. More recently, various energy systems have been applied to the endometrium such as lasers, microwaves, monopolar and bipolar RF, hot fluid balloons, and cryotherapy. They are being used in computer controlled treatments that obviate the user's skill, and utilize a self-positioning device paired with a temperature monitored, thermal treatment. Finite element models have also been created to predict heating profiles with devices that either rely on conductive heating or that deposit power in tissue. This is a very active field in terms of innovation with creative solutions using contemporary technology to reduce or halt the bleeding. Devices and minimally invasive treatments will offer choices to women and will be able to replace a surgical procedure with an office-based procedure. They are very promising and are discussed at length herein.

Abnormal uterine bleeding.

PubMed

Cheong, Ying; Cameron, Iain T; Critchley, Hilary O D

2017-09-01

It is not uncommon for a woman to suffer from abnormal uterine bleeding (AUB) or heavy menstrual bleeding (HMB) at some point during her lifetime. Once pathology is excluded, in practice, management needs to be individualised, taking into account the improvement of the woman's symptoms and quality of life. Peer-reviewed journals, governmental and professional society publications. There is now agreement on a structured, universal approach to the diagnosis of AUB, with the aide memoirs PALM (polyps, adenomyosis, leiomyoma, malignancy) and COEIN (coagulopathies, ovulatory dysfunction, endometrial, iatrogenic, not otherwise classified). Once malignancy and significant pelvic pathology have been ruled out, medical treatment is an effective first-line therapeutic option, with surgery, including endometrial ablation and hysterectomy, offered when medical management has failed to resolve symptoms and fertility is no longer desired. There remains controversy around the management of the types and subtypes of adenomyosis and leiomyoma, and understanding their impact on clinical reproductive outcomes. Standardised assessment tools for measuring outcomes of AUB are being developed. Novel diagnostic and monitoring tools should be developed to help stratify treatment for women with AUB, particularly relating to 'unclassified' and 'endometrial' causes. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Laser treatment in gynecology

NASA Astrophysics Data System (ADS)

de Riese, Cornelia

2004-07-01

This presentation is designed as a brief overview of laser use in gynecology, for non-medical researchers involved in development of new laser techniques. The literature of the past decade is reviewed. Differences in penetration, absorption, and suitable delivery media for the beams dictate clinical application. The use of CO2 laser in the treatment of uterine cervical intraepithelial lesions is well established and indications as well as techniques have not changed over 30 years. The Cochrane Systematic Review from 2000 suggests no obviously superior technique. CO2 laser ablation of the vagina is also established as a safe treatment modality for VAIN. CO2 laser permits treatment of lesions with excellent cosmetic and functional results. The treatment of heavy menstrual bleeding by destruction of the endometrial lining using various techniques has been the subject of a 2002 Cochran Database Review. Among the compared treatment modalities are newer and modified laser techniques. Conclusion by reviewers is that outcomes and complication profiles of newer techniques compare favorably with the gold standard of endometrial resection. The ELITT diode laser system is one of the new successful additions. CO2 laser is also the dominant laser type used with laparoscopy for ablation of endometriotic implants. Myoma coagulation or myolysis with Nd:Yag laser through the laparoscope or hysteroscope is a conservative treatment option. Even MRI guided percutaneous approaches have been described. No long-term data are available.

Predictive diagnosis of endometrial hyperplasia and personalized therapeutic strategy in women of fertile age

PubMed Central

2013-01-01

Introduction Endometrial hyperplasia has a high risk for malignant transformation and relapses; existing mini-invasive treatments may lead to irrevocable endometrium destruction. The aims were to analyze receptor systems in endometrial hyperplasia, to evaluate the capabilities of ultrasonography, sonoelastography for diagnosis and treatment control, and to develop treatment algorithm. Materials and methods We included 313 women (20–45 years), assessed into the following: group 1 (n = 112) with glandular cystic hyperplasia, group 2 (n = 98) endometrial polyps, and group 3 (n = 103) atypical hyperplasia; and 82 controls who have undergone hysteroscopy before in vitro fertilization in tubal origin infertility were also included. Patients underwent clinical examination, transvaginal ultrasound, immunohistochemical study, and hormonal therapy/hysteroresectoscopy. Results In patients with glandular hyperplasia, we registered increase of endometrium estrogen receptors (75.6% in the epithelium and 30.9% in the stroma; in controls, 43.3% and 29.6%, respectively); in polyps, there was a significant estrogen receptor increase in the stroma (48.2% vs 29.6% in controls), and in atypical hyperplasia, progesterone receptors significantly increased in the stroma. Ki-67 increased (40% to 50%) in the epithelium without changes in the stroma. Ultrasound has a sensitivity of 96% and a specificity of 85% for early detection of endometrial pathology and prediction outcome of intervention, and sonoelastography has a sensitivity of 91% and a specificity of 83% for polyp diagnosis. Personalized treatment was effective in 88.8%, relapse was diagnosed in 11.2% after 6 months, and conservative treatment of atypical hyperplasia was effective in 45%: in 25.8%, ablative hysteroresectoscopy was performed, while in 22.6% with comorbidities, hystero/oophorectomies were performed. Conclusions The evaluation of receptor status with ultrasound data in patients with endometrial hyperplasia allows for a clear definition of the treatment policy, avoidance of relapse, treatment optimization, and observation of such patients. PMID:24314145

Atypical polypoid adenomyoma and hysteroscopic endometrial ablation.

PubMed

Vilos, George A; Ettler, Helen C

2003-09-01

A 49-year-old woman presenting with menometrorrhagia underwent an office endometrial biopsy that indicated features suspicious for atypical polypoid adenomyoma (APA) but was inconclusive. The woman requested further evaluation prior to consenting to a hysterectomy and bilateral salpingo-oophorectomy. Hysteroscopy demonstrated a fleshy 2 cm to 3 cm sessile polypoid tumour, which was resected with the entire endometrium. The histology confirmed APA. Although amenorrhea was achieved, the gynaecological oncologist recommended the woman undergo hysterectomy, which she did 4 months later. Pathologic examination of the uterus revealed no residual endometrium or APA. As this tumour generally occurs in premenopausal women, and as conserving fertility potential may be an important consideration, hysteroscopic resection of such tumours may be a therapeutic option in women who wish to retain their uterus or who would be at high medical risk for hysterectomy. However, close, intermittent postoperative surveillance is recommended.

Teaching Surgical Hysteroscopy with a Computer

PubMed

Lefebvre; Cote; Lefebvre

1996-08-01

Using a hysteroscope can be simulated on a computer. It will improve physician training by measuring basic knowledge and abilities, allow different interventions and anatomic variations, minimize the trauma of surgical intervention, and reduce operative casualties. An integrated questionnaire covers instrumentation, fluid infusion, power source, indications and preparation for endometrial ablation, surgical techniques, and complications to evaluate the user's knowledge. The operation simulation then proceeds. In the endometrial cavity, by virtual simulation, the operating field should appear in real time to allow physicians to adapt the trajectory of the instruments. The computer is an IBM PC compatible. We use a modified joystick with optical encoders to know the instrument position. The simulation can be repeated as desired. An evaluation system is integrated in the software to keep the user informed on the amount of burn area(s) that have been completed. This prototype model is available.

Treatment of cornual pregnancy in a patient with adenomyosis by high-intensity focused ultrasound (HIFU) ablation: A case report.

PubMed

Yu, Lixia; Xu, Linying; Xu, Xiaoyan

2017-12-01

Cornual ectopic pregnancy in adenomyosis patients is a rare clinical condition, which may require careful approach for accurate diagnosis and treatment. A 38-year-old woman presented with amenorrhea for 8 weeks and serum HCG levels of 1455 mmol/L. The B ultrasound showed an endometrial thickness of 1.7 cm, and the presence of a cystic structure (16 6 mm) at the right uterine horn. Color Doppler flow imaging (CDFI) accurately detected and confirmed the position of the cystic structure with its clear boundaries. Cornual ectopic pregnancy in adenomyosis. The diagnosis was confirmed and treated by HIFU ablation. Total ablation was performed for 738 seconds without any bleeding. Serum HCG levels decreased to < 0.1 mmol/L after 60 days post operation, and follow-up for 11 months showed a regular menstrual cycle without dysmenorrhea. Gestational sac was not obvious at postoperative 90 days by MRI. The adenomyosis associated lesion with blood perfusion became smaller at postoperative 90 days. In this case, we successfully performed HIFU ablation and treated the cornual ectopic pregnancy in an adenomyosis patient for the first time, without any adverse complications.

The Surgical Treatments Outcomes Project for Dysfunctional Uterine Bleeding: summary of an Agency for Health Research and Quality-sponsored randomized trial of endometrial ablation versus hysterectomy for women with heavy menstrual bleeding.

PubMed

Munro, Malcolm G; Dickersin, Kay; Clark, Melissa A; Langenberg, Patricia; Scherer, Roberta W; Frick, Kevin D

2011-04-01

Surgical Treatments Outcomes Project for Dysfunctional Uterine Bleeding is an agency for the Healthcare Research and Quality project built around a multicenter randomized clinical trial comparing hysterectomy and endometrial ablation (EA) for the treatment of heavy menstrual bleeding unrelated to structural causes. For inclusion, women self-defined their complaint, and the endometrial cavity was evaluated to exclude structural lesions. The primary outcomes were bleeding and major problem "solved" at 24 months, with length of institutional stay, surgical complications, quality of life, and reoperation included as secondary outcomes. Also measured was the baseline economic impact of heavy menstrual bleeding. The randomized controlled trial enrolled 237 women. Institutional stay was longer, and perioperative adverse events were more common and severe for those randomized to hysterectomy. At 24 months, 94.4% and 84.9% of women randomized to hysterectomy and EA, respectively, considered their major problem to be solved; at 48 months, the numbers were similar at 98.0% and 85.1%. Postprocedure quality-of-life measures (SF-36, EuroQOL) improved similarly in both groups, but reoperation was more common for women undergoing EA (34, or 30.9%, at 60 mo), with most (32 of 34) selecting hysterectomy.At baseline, women reported missed work as well as activity and leisure limitations. Excess monetary costs were $306 per patient-year (95% CI, $30-$1,872). Excess work and home management loss costs were $2,152 (95% CI, $1,862-$2,479). It was estimated that successful treatment, regardless of the type of intervention, could result in a gain of 1.8 quality-adjusted life years. Future studies will examine and compare the impact of the study interventions on economic outcomes. © 2011 by The North American Menopause Society

Assessment of uterine cavity size and shape: a systematic review addressing relevance to intrauterine procedures and events.

PubMed

Goldstuck, Norman

2012-09-01

Uterine cavity measurement began with evaluation of post-mortem and surgical specimens. It has been extended in vivo by use of mechanical instruments and visualization techniques. This is a systematic review of the range of values for the uterine cavity and the practical implications of these measurements, Following a review of multiple data bases & a QUORUM analysis. Only articles with clearly defined quantitative measurements were included. Mechanical cavity measurements with a variety of instruments gave a mean endometrial cavity length (ECL) of 33.73 mm (18-22.1) and a mean endometrial cavity width (ECW) of 25.1 mm (17.8-32.2) for nulliparae. The values for multiparae were mean ECL 38.6mm(20.61-40.3) and mean ECW 34.9 mm (23.4-53). Imaging measurements for the uterine cavity by hysterography and ultrasound were mean ECL 44.3 mm (29-64) for multiparae and ECL 37 mm for nulliparae. Mean ECW was 28.2 mm (21-33) for nulliparae and 32.1 mm (26-38) for multiparae. There were wide variations due to parity, ethnicity and gestational states. Accurate measurement of intrauterine parameters is valuable for improving and enhancing many intrauterine procedures including IUD insertion, endometrial ablation, embryo placement in IVF and management of spontaneous and therapeutic abortion.

Heavy menstrual bleeding: An update on management.

PubMed

Davies, Joanna; Kadir, Rezan A

2017-03-01

Heavy menstrual bleeding (HMB) is defined as excessive menstrual blood loss (MBL) >80 mL per cycle, that interferes with a woman's physical, emotional, social wellbeing and quality of life. Aetiology is due to underlying uterine pathologies, coagulopathy, ovulation dysfunction, or iatrogenic. Up to 20% of women with HMB will have an underlying inherited bleeding disorder (IBD). Assessment of HMB should entail a menstrual and gynaecological history and a bleeding score to distinguish those women who require additional haematological investigations. A pelvic examination and ultrasound scan help to rule out presence of any underlying pathology. Management depends on the underlying cause and the woman's preference and her fertility wishes. Medical therapies include hormonal treatments; levonorgestrel-releasing intrauterine system (LNG-IUS) and combined hormonal contraceptives are most commonly used. Ulipristal acetate is an approved preoperative treatment for uterine fibroids, and has demonstrated efficacy in reducing MBL. Haemostatic therapies include tranexamic acid and DDAVP (1-deamino-8-D-arginine). DDAVP is used for HMB associated with certain IBDs. These therapies can be used in isolation or in combination with hormonal treatments. HMB associated with certain severe IBDs may require factor concentrate administration during menses to alleviate symptoms. Endometrial ablation is a minor surgical procedure that is associated with low operative morbidity and can be performed as an outpatient. Hysterectomy remains the definitive treatment of choice when medical therapies have failed and endometrial ablation is not suitable. Crown Copyright © 2017 Published by Elsevier Ltd. All rights reserved.

Combined Endometrial Ablation and Levonorgestrel Intrauterine System Use in Women With Dysmenorrhea and Heavy Menstrual Bleeding: Novel Approach for Challenging Cases.

PubMed

Papadakis, Efstathios P; El-Nashar, Sherif A; Laughlin-Tommaso, Shannon K; Shazly, Sherif A M; Hopkins, Matthew R; Breitkopf, Daniel M; Famuyide, Abimbola O

2015-01-01

To evaluate the feasibility and impact of levonorgestrel intrauterine system (LNG-IUS) on treatment failure after endometrial ablation (EA) in women with heavy menstrual bleeding (HMB) and dysmenorrhea at 4 years. Cohort study (Canadian Task Force II-2). An academic institution in the upper Midwest. All women with HMB and dysmenorrhea who underwent EA with combined placement of LNG-IUS (EA/LNG-IUS cohort, 23 women) after 2005 and an historic reference group from women who had EA alone (EA cohort, 65 women) from 1998 through the end of 2005. Radiofrequency EA, thermal balloon ablation, and LNG-IUS. The primary outcome was treatment failure defined as persistent pain, bleeding, and hysterectomy after EA at 4 years. The combined treatment failure outcome was documented in 2 patients (8.7%) in the EA/LNG-IUS group and 19 patients (29.2%) in the EA group with an unadjusted OR of .23 (95% CI, .05-1.08). After adjusting for known risk factors of failure, the adjusted OR was .19 (95% CI, .26-.88). None of the women who underwent EA/LNG-IUS had hysterectomy for treatment failure compared with 16 (24%) in the EA group (p = .009); postablation pelvic pain was documented in 1 woman (4.3%) in the EA/LNG-IUS group compared with 8 women (12.3%) in the EA group (p = .24). One woman in the EA/LNG-IUS group (4.3%) presented with persistent bleeding compared with 15 (23.1%) in the EA group (p = .059). Office removal of the intrauterine device was performed in 4 women with no complications. LNG-IUS insertion at the time of EA is feasible and can provide added benefit after EA in women with dysmenorrhea and HMB. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

Treatment of cornual pregnancy in a patient with adenomyosis by high-intensity focused ultrasound (HIFU) ablation

PubMed Central

Yu, Lixia; Xu, Linying; Xu, Xiaoyan

2017-01-01

Abstract Rationale: Cornual ectopic pregnancy in adenomyosis patients is a rare clinical condition, which may require careful approach for accurate diagnosis and treatment. Patient concerns: A 38-year-old woman presented with amenorrhea for 8 weeks and serum HCG levels of 1455 mmol/L. The B ultrasound showed an endometrial thickness of 1.7 cm, and the presence of a cystic structure (16 6 mm) at the right uterine horn. Color Doppler flow imaging (CDFI) accurately detected and confirmed the position of the cystic structure with its clear boundaries. Diagnoses: Cornual ectopic pregnancy in adenomyosis. Interventions: The diagnosis was confirmed and treated by HIFU ablation. Total ablation was performed for 738 seconds without any bleeding. Outcomes: Serum HCG levels decreased to < 0.1 mmol/L after 60 days post operation, and follow-up for 11 months showed a regular menstrual cycle without dysmenorrhea. Gestational sac was not obvious at postoperative 90 days by MRI. The adenomyosis associated lesion with blood perfusion became smaller at postoperative 90 days. Lessons: In this case, we successfully performed HIFU ablation and treated the cornual ectopic pregnancy in an adenomyosis patient for the first time, without any adverse complications. PMID:29310371

Loss of Cdh1 and Trp53 in the uterus induces chronic inflammation with modification of tumor microenvironment.

PubMed

Stodden, G R; Lindberg, M E; King, M L; Paquet, M; MacLean, J A; Mann, J L; DeMayo, F J; Lydon, J P; Hayashi, K

2015-05-07

Type II endometrial carcinomas (ECs) are estrogen independent, poorly differentiated tumors that behave in an aggressive manner. As TP53 mutation and CDH1 inactivation occur in 80% of human endometrial type II carcinomas, we hypothesized that mouse uteri lacking both Trp53 and Cdh1 would exhibit a phenotype indicative of neoplastic transformation. Mice with conditional ablation of Cdh1 and Trp53 (Cdh1(d/d)Trp53(d/d)) clearly demonstrate architectural features characteristic of type II ECs, including focal areas of papillary differentiation, protruding cytoplasm into the lumen (hobnailing) and severe nuclear atypia at 6 months of age. Further, Cdh1(d/d)Trp53(d/d) tumors in 12-month-old mice were highly aggressive, and metastasized to nearby and distant organs within the peritoneal cavity, such as abdominal lymph nodes, mesentery and peri-intestinal adipose tissues, demonstrating that tumorigenesis in this model proceeds through the universally recognized morphological intermediates associated with type II endometrial neoplasia. We also observed abundant cell proliferation and complex angiogenesis in the uteri of Cdh1(d/d)Trp53(d/d) mice. Our microarray analysis found that most of the genes differentially regulated in the uteri of Cdh1(d/d)Trp53(d/d) mice were involved in inflammatory responses. CD163 and Arg1, markers for tumor-associated macrophages, were also detected and increased in the uteri of Cdh1(d/d)Trp53(d/d) mice, suggesting that an inflammatory tumor microenvironment with immune cell recruitment is augmenting tumor development in Cdh1(d/d)Trp53(d/d) uteri. Further, inflammatory mediators secreted from CDH1-negative, TP53 mutant endometrial cancer cells induced normal macrophages to express inflammatory-related genes through activation of nuclear factor-κB signaling. These results indicate that absence of CDH1 and TP53 in endometrial cells initiates chronic inflammation, promotes tumor microenvironment development following the recruitment of macrophages and promotes aggressive ECs.

[Analysis from the French DRG-based information system (PMSI) of conservative surgical treatment for abnormal uterine bleeding in 2008-2010].

PubMed

Fernandez, H; Villefranque, V; Panel, P

2015-05-01

To evaluate the conservative surgical treatment for abnormal uterine bleeding from the Medicalized Information System Program (PMSI). The diagnosis codes were selected from 10th version of the international classification disease. A transversal and longitudinal descriptive analysis was performed from hospital stays, patient's characteristics, medical procedures between 2008-2010. Nineteen thousand six hundred and seventy-nine patients were admitted in hospital (public or private) for treatment of abnormal uterine bleeding. Endometrial ablation increased by 16,7%, 10.2% for first generation technique (G1) and 63.5% for second generation techniques (G2). G2 were used in 15% of indications. The median age was respectively 45.2±6.4 years old versus 45.8±4.9 years old for G2. The median length of hospital stay was 1.6 ±1with 69% of patients in ambulatory care. The likelihood to have a hysterectomy in the 3 years follow-up was higher after G1 than G2 treatments (P=0.0034) for the patients above 40 years old. In longitudinal study, defined only by endometrial hyperplasia, 11,532 patients were included and only 8.2% had been treated by G2. In spite of the international guidelines since 2008, 85% of patients treated with first generation surgical technique. The failure rate defined by a re-ablation or a hysterectomy is higher after G1. This result must be discussed in relationship with cost effective aspects. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Intraoperative microwave ablation of pulmonary malignancies with tumor permittivity feedback control: ablation and resection study in 10 consecutive patients.

PubMed

Wolf, Farrah J; Aswad, Bassam; Ng, Thomas; Dupuy, Damian E

2012-01-01

To determine histologic changes induced by microwave ablation (MWA) in patients with pulmonary malignancy by using an ablation system with tumor permittivity feedback control, enabling real-time modulation of energy power and frequency. Institutional review board approval and patient informed consent were obtained for this prospective HIPAA-complaint ablation and resection study. Between March 2009 and January 2010, 10 patients (four women, six men; mean age, 71 years; age range, 52-82 years) underwent intraoperative MWA of pulmonary malignancies. Power (10-32 W) and frequency (908-928 MHz) were continuously adjusted by the generator to maintain a temperature of 110°-120°C at the 14-gauge antenna tip for one 10-minute application. After testing for an air leak, tumors were resected surgically. Gross inspection, slicing, and hematoxylin-eosin (10 specimens) and nicotinamide adenine dinucleotide (six specimens) staining were performed. Tumors included adenocarcinomas (n = 5), squamous cell carcinomas (n = 3), and metastases from endometrial (n = 1) and colorectal (n = 1) primary carcinomas. Mean maximum tumor diameter was 2.4 cm (range, 0.9-5.0 cm), and mean maximum volume was 8.6 cm(3) (range, 0.5-52.7 cm(3)). One air leak was detected. Five of 10 specimens were grossly measurable, revealing a mean maximum ablation zone diameter of 4.8 cm (range, 3.0-6.5 cm) and a mean maximum ablation zone volume of 15.1 cm(3) (range, 7.3-25.1 cm(3)). At hematoxylin-eosin staining, coagulation necrosis was observed in all ablation zones, extended into the normal lung in nine of 10 specimens, and up to blood vessel walls without evidence of vessel (>4 mm) thrombosis. Nicotinamide adenine dinucleotide staining enabled confirmation of no viability within ablation zones extending into normal lung in five of six specimens. MWA with tumor permittivity feedback control results in cytotoxic intratumoral temperatures and extension of ablation zones into aerated peritumoral pulmonary parenchyma, possibly forming the equivalent of an oncologic resection margin. © RSNA, 2011.

WNT4 is a key regulator of normal postnatal uterine development and progesterone signaling during embryo implantation and decidualization in the mouse

PubMed Central

Franco, Heather L.; Dai, Daisy; Lee, Kevin Y.; Rubel, Cory A.; Roop, Dennis; Boerboom, Derek; Jeong, Jae-Wook; Lydon, John P.; Bagchi, Indrani C.; Bagchi, Milan K.; DeMayo, Francesco J.

2011-01-01

WNT4, a member of the Wnt family of ligands, is critical for the development of the female reproductive tract. Analysis of Wnt4 expression in the adult uterus during pregnancy indicates that it may play a role in the regulation of endometrial stromal cell proliferation, survival, and differentiation, which is required to support the developing embryo. To investigate the role of Wnt4 in adult uterine physiology, conditional ablation of Wnt4 using the PRcre mouse model was accomplished. Ablation of Wnt4 rendered female mice subfertile due to a defect in embryo implantation and subsequent defects in endometrial stromal cell survival, differentiation, and responsiveness to progesterone signaling. In addition to altered stromal cell function, the uteri of PRcre/+Wnt4f/f (Wnt4d/d) mice displayed altered epithelial differentiation characterized by a reduction in the number of uterine glands and the emergence of a p63-positive basal cell layer beneath the columnar luminal epithelial cells. The altered epithelial cell phenotype was further escalated by chronic estrogen treatment, which caused squamous cell metaplasia of the uterine epithelium in the Wnt4d/d mice. Thus, WNT4 is a critical regulator not only of proper postnatal uterine development, but also embryo implantation and decidualization.—Franco, H. L., Dai, D., Lee, K. Y., Rubel, C. S., Roop, D., Boerboom, D., Jeong, J.-W., Lydon, J.-P., Bagchi, I. C., Bagchi, M. K., DeMayo, F. J. WNT4 is a key regulator of normal postnatal uterine development and progesterone signaling during embryo implantation and decidualization in the mouse. PMID:21163860

Rac1 Regulates Endometrial Secretory Function to Control Placental Development.

PubMed

Davila, Juanmahel; Laws, Mary J; Kannan, Athilakshmi; Li, Quanxi; Taylor, Robert N; Bagchi, Milan K; Bagchi, Indrani C

2015-08-01

During placenta development, a succession of complex molecular and cellular interactions between the maternal endometrium and the developing embryo ensures reproductive success. The precise mechanisms regulating this maternal-fetal crosstalk remain unknown. Our study revealed that the expression of Rac1, a member of the Rho family of GTPases, is markedly elevated in mouse decidua on days 7 and 8 of gestation. To investigate its function in the uterus, we created mice bearing a conditional deletion of the Rac1 gene in uterine stromal cells. Ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that Rac1 signaling regulates the expression of Rab27b, another GTPase that plays a key role in targeting vesicular trafficking. Consequently, the Rac1-null decidual cells failed to secrete vascular endothelial growth factor A, which is a critical regulator of decidual angiogenesis, and insulin-like growth factor binding protein 4, which regulates the bioavailability of insulin-like growth factors that promote proliferation and differentiation of trophoblast cell lineages in the ectoplacental cone. The lack of secretion of these key factors by Rac1-null decidua gave rise to impaired angiogenesis and dysregulated proliferation of trophoblast cells, which in turn results in overexpansion of the trophoblast giant cell lineage and disorganized placenta development. Further experiments revealed that RAC1, the human ortholog of Rac1, regulates the secretory activity of human endometrial stromal cells during decidualization, supporting the concept that this signaling G protein plays a central and conserved role in controlling endometrial secretory function. This study provides unique insights into the molecular mechanisms regulating endometrial secretions that mediate stromal-endothelial and stromal-trophoblast crosstalk critical for placenta development and establishment of pregnancy.

The Role of Hysteroscopy in the Diagnosis and Treatment of Adenomyosis.

PubMed

Di Spiezio Sardo, Attilio; Calagna, Gloria; Santangelo, Fabrizia; Zizolfi, Brunella; Tanos, Vasilis; Perino, Antonino; De Wilde, Rudy Leon

2017-01-01

Uterine adenomyosis is a common gynecologic disorder in women of reproductive age, characterized by the presence of ectopic endometrial glands and stroma within the myometrium. Dysmenorrhea, abnormal uterine bleeding, chronic pelvic pain, and deep dyspareunia are common symptoms of this pathological condition. However, adenomyosis is often an incidental finding in specimens obtained from hysterectomy or uterine biopsies. The recent evolution of diagnostic imaging techniques, such as transvaginal sonography, hysterosalpingography, and magnetic resonance imaging, has contributed to improving accuracy in the identification of this pathology. Hysteroscopy offers the advantage of direct visualization of the uterine cavity while giving the option of collecting histological biopsy samples under visual control. Hysteroscopy is not a first-line treatment approach for adenomyosis and it represents a viable option only in selected cases of focal or diffuse "superficial" forms. During office hysteroscopy, it is possible to enucleate superficial focal adenomyomas or to evacuate cystic haemorrhagic lesions of less than 1.5 cm in diameter. Instead, resectoscopic treatment is indicated in cases of superficial adenomyotic nodules > 1.5 cm in size and for diffuse superficial adenomyosis. Finally, endometrial ablation may be performed with the additional removal of the underlying myometrium.

Computer modeling of electromagnetic and thermal effects in microwave soft tissue ablation (Invited Paper)

NASA Astrophysics Data System (ADS)

Cronin, Nigel J.; Clegg, Peter J.

2005-04-01

Microwave Endometrial Ablation (MEA) is a technique that can be used for the treatment of abnormal uterine bleeding. The procedure involves sweeping a specially designed microwave applicator throughout the uterine cavity to achieve an ideally uniform depth of tissue necrosis of between 5 and 6mm. We have performed a computer analysis of the MEA procedure in which finite element analysis was used to determine the SAR pattern around the applicator. This was followed by a Green Function based solution of the Bioheat equation to determine the resulting induced temperatures. The method developed is applicable to situations involving a moving microwave source, as used in MEA. The validity of the simulation was verified by measurements in a tissue phantom material using a purpose built applicator and a calibrated pulling device. From the calculated temperatures the depth of necrosis was assessed through integration of the resulting rates of cell death estimated using the Arrhenius equation. The Arrhenius parameters used were derived from published data on BHK cells. Good agreement was seen between the calculated depths of cell necrosis and those found in human in-vivo testing.

Pelvic denervation procedures for dysmenorrhea.

PubMed

Ramirez, Christina; Donnellan, Nicole

2017-08-01

Chronic pelvic pain and dysmenorrhea are common conditions affecting reproductive-age women. Surgical pelvic denervation procedures may be a treatment option for women with midline dysmenorrhea, in which medical management is declined by the patient, ineffective at managing symptoms, or medically contraindicated. This review describes the surgical techniques and complications associated with pelvic denervation procedures as well as the current evidence for these procedures in women with primary dysmenorrhea and dysmenorrhea secondary to endometriosis. Presacral neurectomy is the preferred pelvic denervation procedure in patients with primary dysmenorrhea and midline chronic pelvic pain associated with endometriosis. In patients with endometriosis presacral neurectomy is a useful adjunct to excision or ablation of all endometrial lesions to improve postoperative pain relief. There is no additional patient benefit of performing combined presacral neurectomy and uterine nerve ablation procedures. Pelvic denervation procedures can be performed safely and quickly with a low risk of complication if the surgeon is knowledgeable and skilled in operating in the presacral space. Patients should be adequately counseled on expected success rates and potential complications associated with pelvic denervation procedures.

Megestrol Acetate or Levonorgestrel-Releasing Intrauterine System in Treating Patients With Atypical Endometrial Hyperplasia or Endometrial Cancer

ClinicalTrials.gov

2014-09-09

Atypical Endometrial Hyperplasia; Endometrial Adenocarcinoma; Recurrent Endometrial Carcinoma; Stage IA Endometrial Carcinoma; Stage IB Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma

An inducible knockout mouse to model the cell-autonomous role of PTEN in initiating endometrial, prostate and thyroid neoplasias.

PubMed

Mirantes, Cristina; Eritja, Núria; Dosil, Maria Alba; Santacana, Maria; Pallares, Judit; Gatius, Sónia; Bergadà, Laura; Maiques, Oscar; Matias-Guiu, Xavier; Dolcet, Xavier

2013-05-01

PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. The role of PTEN in carcinogenesis has been validated by knockout mouse models. PTEN heterozygous mice develop neoplasms in multiple organs. Unfortunately, the embryonic lethality of biallelic excision of PTEN has inhibited the study of complete PTEN deletion in the development and progression of cancer. By crossing PTEN conditional knockout mice with transgenic mice expressing a tamoxifen-inducible Cre-ER(T) under the control of a chicken actin promoter, we have generated a tamoxifen-inducible mouse model that allows temporal control of PTEN deletion. Interestingly, administration of a single dose of tamoxifen resulted in PTEN deletion mainly in epithelial cells, but not in stromal, mesenchymal or hematopoietic cells. Using the mT/mG double-fluorescent Cre reporter mice, we demonstrate that epithelial-specific PTEN excision was caused by differential Cre activity among tissues and cells types. Tamoxifen-induced deletion of PTEN resulted in extremely rapid and consistent formation of endometrial in situ adenocarcinoma, prostate intraepithelial neoplasia and thyroid hyperplasia. We also analyzed the role of PTEN ablation in other epithelial cells, such as the tubular cells of the kidney, hepatocytes, colonic epithelial cells or bronchiolar epithelium, but those tissues did not exhibit neoplastic growth. Finally, to validate this model as a tool to assay the efficacy of anti-tumor drugs in PTEN deficiency, we administered the mTOR inhibitor everolimus to mice with induced PTEN deletion. Everolimus dramatically reduced the progression of endometrial proliferations and significantly reduced thyroid hyperplasia. This model could be a valuable tool to study the cell-autonomous mechanisms involved in PTEN-loss-induced carcinogenesis and provides a good platform to study the effect of anti-neoplastic drugs on PTEN-negative tumors.

An inducible knockout mouse to model the cell-autonomous role of PTEN in initiating endometrial, prostate and thyroid neoplasias

PubMed Central

Mirantes, Cristina; Eritja, Núria; Dosil, Maria Alba; Santacana, Maria; Pallares, Judit; Gatius, Sónia; Bergadà, Laura; Maiques, Oscar; Matias-Guiu, Xavier; Dolcet, Xavier

2013-01-01

SUMMARY PTEN is one of the most frequently mutated tumor suppressor genes in human cancers. The role of PTEN in carcinogenesis has been validated by knockout mouse models. PTEN heterozygous mice develop neoplasms in multiple organs. Unfortunately, the embryonic lethality of biallelic excision of PTEN has inhibited the study of complete PTEN deletion in the development and progression of cancer. By crossing PTEN conditional knockout mice with transgenic mice expressing a tamoxifen-inducible Cre-ERT under the control of a chicken actin promoter, we have generated a tamoxifen-inducible mouse model that allows temporal control of PTEN deletion. Interestingly, administration of a single dose of tamoxifen resulted in PTEN deletion mainly in epithelial cells, but not in stromal, mesenchymal or hematopoietic cells. Using the mT/mG double-fluorescent Cre reporter mice, we demonstrate that epithelial-specific PTEN excision was caused by differential Cre activity among tissues and cells types. Tamoxifen-induced deletion of PTEN resulted in extremely rapid and consistent formation of endometrial in situ adenocarcinoma, prostate intraepithelial neoplasia and thyroid hyperplasia. We also analyzed the role of PTEN ablation in other epithelial cells, such as the tubular cells of the kidney, hepatocytes, colonic epithelial cells or bronchiolar epithelium, but those tissues did not exhibit neoplastic growth. Finally, to validate this model as a tool to assay the efficacy of anti-tumor drugs in PTEN deficiency, we administered the mTOR inhibitor everolimus to mice with induced PTEN deletion. Everolimus dramatically reduced the progression of endometrial proliferations and significantly reduced thyroid hyperplasia. This model could be a valuable tool to study the cell-autonomous mechanisms involved in PTEN-loss-induced carcinogenesis and provides a good platform to study the effect of anti-neoplastic drugs on PTEN-negative tumors. PMID:23471917

Abnormal uterine bleeding in perimenopause.

PubMed

Goldstein, S R; Lumsden, M A

2017-10-01

Abnormal uterine bleeding is one of the commonest presenting complaints encountered in a gynecologist's office or primary-care setting. The wider availability of diagnostic tools has allowed prompt diagnosis and treatment of an increasing number of menstrual disorders in an office setting. This White Paper reviews the advantages and disadvantages of transvaginal ultrasound, blind endometrial sampling and diagnostic hysteroscopy. Once a proper diagnosis has been established, appropriate therapy may be embarked upon. Fortunately, only a minority of such patients will have premalignant or malignant disease. When bleeding is sufficient to cause severe anemia or even hypovolemia, prompt intervention is called for. In most of the cases, however, the abnormal uterine bleeding will be disquieting to the patient and significantly affect her 'quality of life'. Sometimes, reassurance and expectant management will be sufficient in such patients. Overall, however, in cases of benign disease, some intervention will be required. The use of oral contraceptive pills especially those with a short hormone-free interval, the insertion of the levonorgestrel intrauterine system, the incorporation of newer medical therapies including antifibrinolytic drugs and selective progesterone receptor modulators and minimally invasive treatments have made outpatient therapy increasingly effective. For others, operative hysteroscopy and endometrial ablation are proven therapeutic tools to provide both long- and short-term relief of abnormal uterine bleeding, thus avoiding, or deferring, hysterectomy.

Dalantercept in Treating Patients With Recurrent or Persistent Endometrial Cancer

ClinicalTrials.gov

2018-02-13

Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma

Brivanib Alaninate in Treating Patients With Recurrent or Persistent Endometrial Cancer

ClinicalTrials.gov

2017-11-02

Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma

Management of female-to-male transgender persons: medical and surgical management, life expectancy.

PubMed

Gooren, Louis J

2014-06-01

Hormonal treatment of transgender people is becoming a normal part of medicine, though numbers of subjects remain small because of low prevalence. Information on treatment is scattered and this review brings together the latest information on treatment goals and potential side-effects of androgen treatment of female-to-male transsexual subjects. Androgen treatment of female-to-male transsexuals is usually uneventful, with a good patient compliance. Goals of hormonal treatment are elimination of secondary sex characteristics of the female sex and induction of those of the male sex. Completion takes approximately 2 years. Hormonal treatment is eventually followed by surgical ablation of breasts and removal of uterus and ovaries. Phalloplasty may be considered. Concerns are the sequelae of hypogonadism following surgery, such as loss of bone mass. Contrary to earlier expectations, there is no increase in cardiovascular disease. (Hormone-related) cancers are rare, but vaginal, cervical, endometrial carcinomas have been reported. Cancers of the breasts are of greater concern and have been found in residual mammary tissue after breast ablation. So far, androgen treatment has not raised major safety concerns. Regrets about changing sex have not been reported. Testosterone treatment of female-to-male transsexuals is effective and well tolerated.

Thalidomide in Treating Patients With Recurrent or Persistent Endometrial Cancer

ClinicalTrials.gov

2013-01-23

Endometrial Adenoacanthoma; Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma

Nintedanib in Treating Patients With Recurrent or Persistent Endometrial Cancer

ClinicalTrials.gov

2017-09-08

Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Malignant Uterine Corpus Mixed Epithelial and Mesenchymal Neoplasm; Recurrent Uterine Corpus Carcinoma

Liquid-Based Endometrial Cytology Using SurePath™ Is Not Inferior to Suction Endometrial Tissue Biopsy in Clinical Performance for Detecting Endometrial Cancer Including Atypical Endometrial Hyperplasia.

PubMed

Yanaki, Fumiko; Hirai, Yasuo; Hanada, Azusa; Ishitani, Ken; Matsui, Hideo

2017-01-01

We evaluated the clinical performance of liquid-based endometrial cytology (SurePath™) for detecting endometrial malignancies by comparison with the performance of suction endometrial tissue biopsy. From November 2011 to May 2013, we consecutively collected 1,118 liquid-based endometrial cytology specimens and 674 suction endometrial tissue biopsy specimens. The rate of nonpositive final histology in nonpositive liquid-based endometrial cytology (98.2%) was higher than the rate of nonpositive final histology in nonpositive suction endometrial tissue biopsy (97.0%). None of the clinical performance values of liquid-based endometrial cytology for detecting the endometrial malignancies were statistically inferior to those of the suction endometrial tissue biopsy. When the positivity threshold was more than "atypical endometrial cells of undetermined significance," the rate of positive liquid-based endometrial cytology from cases with a positive final histology (84.5%) was higher than the rate of positive suction endometrial tissue biopsy from cases with a positive final histology (69.8%). However, there were still no significant differences among all the performance values. Our liquid-based endometrial cytology would be more appropriate in various clinical situations as the initial detection tool for endometrial malignancies, rather than suction endometrial tissue biopsy. In addition, it could be used in screening for endometrial malignancies on a broader scale. © 2017 S. Karger AG, Basel.

Endometrial cancer arising from atypical complex hyperplasia: The significance in an endometrial biopsy and a diagnostic challenge

PubMed Central

Byun, Jung Mi; Jeong, Dae Hoon; Kim, Young Nam; Cho, En Bee; Cha, Ju Eun; Sung, Moon Su; Lee, Kyung Bok

2015-01-01

Objective We investigated the features of endometrial hyperplasia with concurrent endometrial cancer that had been diagnosed by endometrial sampling. Further, we attempted to identify an accurate differential diagnostic method. Methods We retrospectively studied 125 patients who underwent a diagnostic endometrial biopsy or were diagnosed after the surgical treatment of other gynecological lesions, such as leiomyoma or polyps. Patients were diagnosed between January 2005 and December 2013 at Busan Paik Hospital. Clinical and histopathological characteristics were compared in patients who had atypical endometrial hyperplasia with and without concurrent endometrial cancer. Results The patients were grouped based on the final pathology reports. One hundred seventeen patients were diagnosed with endometrial hyperplasia and eight patients were diagnosed with endometrioid adenocarcinoma arising from atypical hyperplasia. Of the 26 patients who had been diagnosed with atypical endometrial hyperplasia by office-based endometrial biopsy, eight (30.8%) were subsequently diagnosed with endometrial cancer after they had undergone hysterectomy. The patients with endometrial cancer arising from endometrial hyperplasia were younger (39.1 vs. 47.2 years, P=0.0104) and more obese (body mass index 26.1±9.6 vs. 23.8±2.8 kg/m2, P=0.3560) than the patients with endometrial hyperplasia. The correlation rate between the pathology of the endometrial samples and the final diagnosis of endometrial hyperplasia was 67.3%. Conclusion In patients with atypical endometrial hyperplasia, the detection of endometrial cancer before hysterectomy can decrease the risk of suboptimal treatment. The accuracy of endometrial sampling for the diagnosis of concurrent endometrial carcinoma was much lower than that for atypical endometrial hyperplasia. Therefore, concurrent endometrial carcinoma should be suspected and surgical intervention should be considered in young or obese patients who present with atypical endometrial hyperplasia. PMID:26623410

Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization: current clinical status

NASA Astrophysics Data System (ADS)

Marcus, Stuart L.; Golub, Allyn L.; Shulman, D. Geoffrey

1995-03-01

Photodynamic therapy using 5-aminolevulinic acid-induced photosensitization (ALA PDT) via endogenous protoporphyrin IX (PpIX) synthesis has been reported as efficacious, using topical formulations, in the treatment of a variety of dermatologic diseases including superficial basal cell carcinoma, Bowen's disease, and actinic (solar) keratoses. Application of ALA PDT to the detection and treatment of both malignant and non-malignant diseases of internal organs has recently been reported. Local internal application of ALA has been used for the detection, via PpIX fluorescence, of pathological conditions of the human urinary bladder and for selective endometrial ablation in animal model systems. Systemic, oral administration of ALA has been used for ALA PDT of superficial head and neck cancer and of colorectal cancer. This paper reviews the current clinical status of ALA PDT.

The accuracy of endometrial sampling in women with postmenopausal bleeding: a systematic review and meta-analysis.

PubMed

van Hanegem, Nehalennia; Prins, Marileen M C; Bongers, Marlies Y; Opmeer, Brent C; Sahota, Daljit Singh; Mol, Ben Willem J; Timmermans, Anne

2016-02-01

Postmenopausal bleeding (PMB) can be the first sign of endometrial cancer. In case of thickened endometrium, endometrial sampling is often used in these women. In this systematic review, we studied the accuracy of endometrial sampling for the diagnoses of endometrial cancer, atypical hyperplasia and endometrial disease (endometrial pathology, including benign polyps). We systematically searched the literature for studies comparing the results of endometrial sampling in women with postmenopausal bleeding with two different reference standards: blind dilatation and curettage (D&C) and hysteroscopy with histology. We assessed the quality of the detected studies by the QUADAS-2 tool. For each included study, we calculated the fraction of women in whom endometrial sampling failed. Furthermore, we extracted numbers of cases of endometrial cancer, atypical hyperplasia and endometrial disease that were identified or missed by endometrial sampling. We detected 12 studies reporting on 1029 women with postmenopausal bleeding: five studies with dilatation and curettage (D&C) and seven studies with hysteroscopy as a reference test. The weighted sensitivity of endometrial sampling with D&C as a reference for the diagnosis of endometrial cancer was 100% (range 100-100%) and 92% (71-100) for the diagnosis of atypical hyperplasia. Only one study reported sensitivity for endometrial disease, which was 76%. When hysteroscopy was used as a reference, weighted sensitivities of endometrial sampling were 90% (range 50-100), 82% (range 56-94) and 39% (21-69) for the diagnosis of endometrial cancer, atypical hyperplasia and endometrial disease, respectively. For all diagnosis studied and the reference test used, specificity was 98-100%. The weighted failure rate of endometrial sampling was 11% (range 1-53%), while insufficient samples were found in 31% (range 7-76%). In these women with insufficient or failed samples, an endometrial (pre) cancer was found in 7% (range 0-18%). In women with postmenopausal bleeding, the sensitivity of endometrial sampling to detect endometrial cancer and especially atypical hyperplasia and endometrial disease, including endometrial polyps, is lower than previously thought. Therefore, further diagnostic work-up for focal pathology is warranted, after a benign result of endometrial sampling. Copyright © 2015. Published by Elsevier Ireland Ltd.

Radiation Therapy With or Without Cisplatin in Treating Patients With Recurrent Endometrial Cancer

ClinicalTrials.gov

2018-02-14

Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma

Comparison of Two Combination Chemotherapy Regimens Plus Radiation Therapy in Treating Patients With Stage III or Stage IV Endometrial Cancer

ClinicalTrials.gov

2015-04-30

Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Endometrial Serous Adenocarcinoma; Stage III Uterine Corpus Cancer

Prediction of concurrent endometrial carcinoma in women with endometrial hyperplasia.

PubMed

Matsuo, Koji; Ramzan, Amin A; Gualtieri, Marc R; Mhawech-Fauceglia, Paulette; Machida, Hiroko; Moeini, Aida; Dancz, Christina E; Ueda, Yutaka; Roman, Lynda D

2015-11-01

Although a fraction of endometrial hyperplasia cases have concurrent endometrial carcinoma, patient characteristics associated with concurrent malignancy are not well described. The aim of our study was to identify predictive clinico-pathologic factors for concurrent endometrial carcinoma among patients with endometrial hyperplasia. A case-control study was conducted to compare endometrial hyperplasia in both preoperative endometrial biopsy and hysterectomy specimens (n=168) and endometrial carcinoma in hysterectomy specimen but endometrial hyperplasia in preoperative endometrial biopsy (n=43). Clinico-pathologic factors were examined to identify independent risk factors of concurrent endometrial carcinoma in a multivariate logistic regression model. The most common histologic subtype in preoperative endometrial biopsy was complex hyperplasia with atypia [CAH] (n=129) followed by complex hyperplasia without atypia (n=58) and simple hyperplasia with or without atypia (n=24). The majority of endometrial carcinomas were grade 1 (86.0%) and stage I (83.7%). In multivariate analysis, age 40-59 (odds ratio [OR] 3.07, p=0.021), age≥60 (OR 6.65, p=0.005), BMI≥35kg/m(2) (OR 2.32, p=0.029), diabetes mellitus (OR 2.51, p=0.019), and CAH (OR 9.01, p=0.042) were independent predictors of concurrent endometrial carcinoma. The risk of concurrent endometrial carcinoma rose dramatically with increasing number of risk factors identified in multivariate model (none 0%, 1 risk factor 7.0%, 2 risk factors 17.6%, 3 risk factors 35.8%, and 4 risk factors 45.5%, p<0.001). Hormonal treatment was associated with decreased risk of concurrent endometrial cancer in those with ≥3 risk factors. Older age, obesity, diabetes mellitus, and CAH are predictive of concurrent endometrial carcinoma in endometrial hyperplasia patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Diagnostic utility of three-dimensional power Doppler ultrasound for postmenopausal bleeding.

PubMed

Kim, Ari; Lee, Ji Young; Chun, Sungwook; Kim, Heung Yeol

2015-06-01

We evaluated the role of three-dimensional power Doppler ultrasound (3D PD-US) to detect endometrial lesions in women with postmenopausal endometrial bleeding. In this prospective observational study, from January 2009 to November 2012, we recruited 225 postmenopausal women with postmenopausal uterine bleeding who met the study criteria. Women who had hematologic disease, chronic medical diseases, or nonuterine pelvic diseases were excluded. Prior to endometrial biopsy, the patients underwent a baseline transvaginal ultrasound screening. The vascular indices and endometrial volumes were calculated with 3D PD-US and compared with the endometrial histopathology. Among the endometrial histopathologic findings of 174 women, atrophic endometrium was the most common finding (30.5%). Endometrial malignancy was confirmed in 28 cases (16.1%), and endometrial hyperplasia was diagnosed in 17 cases (9.8%). The prevalence of endometrial cancer was high in patients who had endometrial thickness >9.5 mm (p < 0.001) and volume greater than 4.05 mL (p < 0.001). For the endometrial carcinoma only, the cutoff values of vascular index, flow index, and vascular flow index for predicting malignancy were 13.070, 12.610, and 3.764, respectively. For endometrial hyperplasia, endometrial thickness and vascular flow index were significant findings. Endometrial vasculature and volume can be obtained using 3D PD-US. The diagnostic usefulness of 3D PD-US for endometrial diseases is promising in women with postmenopausal endometrial bleeding. Copyright © 2015. Published by Elsevier B.V.

Copanlisib in Treating Patients With Persistent or Recurrent Endometrial Cancer

ClinicalTrials.gov

2018-02-14

Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Metastatic Endometrioid Adenocarcinoma; PIK3CA Gene Mutation; Recurrent Uterine Corpus Carcinoma

VSV-hIFNbeta-NIS in Treating Patients With Stage IV or Recurrent Endometrial Cancer

ClinicalTrials.gov

2018-05-09

Endometrial Clear Cell Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Metastatic Endometrioid Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Recurrent Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IV Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

Dasatinib, Paclitaxel, and Carboplatin in Treating Patients With Stage III-IV or Recurrent Endometrial Cancer

ClinicalTrials.gov

2018-04-04

Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Endometrioid Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage III Uterine Corpus Cancer AJCC v7; Stage IIIA Uterine Corpus Cancer AJCC v7; Stage IIIB Uterine Corpus Cancer AJCC v7; Stage IIIC Uterine Corpus Cancer AJCC v7; Stage IV Uterine Corpus Cancer AJCC v7; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7

[Hematometra & Listeria monocytogenes].

PubMed

Gómez Arzapalo, E; Pérez Mendizábal, A; Herrera Avalos, I; Gorozpe Calvillo, J I

2001-05-01

The hematometra is a nosological entity that may not always be attributed to an embryonic defect of the paramesonefros; cervical-vaginal infections such as etiological possibilities due to Listeria monocytogenes (Lm), cervix malignant neoplasias, iatrogenias due to endometrial ablation with Lasser, traumatic bloody uterine curetage and because of cervical cryocoagulation or electrocoagulation are also mentioned. The case to be reported is from a woman in reproductive stage, who is 32 years old, and had menarca at the age of 13, starting her sexual life at 31, not using any method to control her fertility. When having an eight-week amenorrhea after 8 months of marriage, she visited the doctor for assumed pregnancy, within the prenatal analysis a pelvic echographic study was requested, finding out images that we concluded as hematometra, having been drained and demonstrated the presence of LM by anti-Lm antibodies, being administered Azitromicina and Espiramicina.

Correlation between three-dimensional power Doppler and morphometric measurement of endometrial vascularity at the time of embryo implantation in women with unexplained recurrent miscarriage.

PubMed

Chen, Xiaoyan; Saravelos, Sotirios H; Liu, Yingyu; Huang, Jin; Wang, Chi Chiu; Li, Tin Chiu

2017-06-01

Power Doppler in combination with three-dimensional (3D-PD) ultrasonography has been used as a noninvasive tool to evaluate the vascularity. However, it is unclear whether 3D-PD can accurately reflect endometrial vascularization and replace the invasive endometrial biopsy. This study aims to investigate the correlation between 3D-PD and micro vessel morphometric measurement of endometrial vascularity. Twenty-five women with unexplained recurrent miscarriage were recruited for 3D-PD and endometrial biopsy on precisely day LH + 7. Immunohistochemistry using vWF was employed to identify micro vessels in endometrial biopsy specimens followed by the use of morphometric technique to measure the mean vessel diameter and volume fractions. The vascularization index (VI), flow index (FI) and vascularization flow index (VFI) assessed by 3D-PD were calculated for both the endometrial and sub-endometrial regions. There were no significant correlations between any of the ultrasonographic measurements (endometrial thickness, endometrial volume, endometrial VI/FI/VFI, sub-endometrial volume, sub-endometrial VI/FI/VFI) and morphometric features (number of micro vessel, mean diameter of micro vessel and volume fraction measurement of vessel). This study indicates that endometrial vascularity assessed by 3D-PD could not be used to reflect changes in micro vessels of the endometrium at the time of embryo implantation in women with unexplained recurrent miscarriage.

Endometrial thickness and risk of breast and endometrial carcinomas in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

PubMed Central

Felix, Ashley S.; Weissfeld, Joel L.; Pfeiffer, Ruth M.; Modugno, Francesmary; Black, Amanda; Hill, Lyndon M.; Martin, Jerry; Sit, Anita S.; Sherman, Mark E.; Brinton, Louise A.

2013-01-01

Postmenopausal women with higher circulating estrogen levels are at increased risk of developing breast and endometrial carcinomas. In the endometrium, excess estrogen relative to progesterone produces a net proliferative stimulus, which may result in endometrial thickening. Therefore, we tested the hypothesis that endometrial thickness is a biological marker of excess estrogen stimulation that is associated with risk of breast and endometrial carcinomas. Endometrial thickness was measured in 1,272 postmenopausal women, aged 55–74, who underwent transvaginal ultrasound (TVU) screening as part of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Serial endometrial thickness measurements were available for a subset of women at one (n=1,018), two (n=869) and three years (n=641) after baseline. We evaluated associations between endometrial thickness and breast (n=91) and endometrial (n=14) carcinoma by estimating relative risks (RRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression with age as the time metric. Models incorporating baseline endometrial thickness and as a time-varying covariate using all measurements were examined. Median follow-up among study participants was 12.5 years (range: 0.3–13.8 years). Compared to baseline endometrial thickness of 1.0 – 2.99 mm, women with baseline endometrial thickness greater than or equal to 5.0 mm had an increased risk of breast (RR: 2.00, 95% CI 1.15, 3.48) and endometrial (RR: 5.02, 95% CI 0.96, 26.36) carcinomas in models adjusted for menopausal hormone use and BMI. Our data suggest that increased endometrial thickness as assessed by TVU was associated with increased risk of breast and endometrial carcinomas. PMID:23907658

The clinicopathologic significance of the loss of BAF250a (ARID1A) expression in endometrial carcinoma.

PubMed

Zhang, Zheng-mao; Xiao, Shuang; Sun, Guang-yu; Liu, Yue-ping; Zhang, Feng-hua; Yang, Hong-fang; Li, Jia; Qiu, Hong-bing; Liu, Yang; Zhang, Chao; Kang, Shan; Shan, Bao-en

2014-03-01

AT-rich interactive domain 1A (ARID1A) is a tumor suppressor gene that encodes the BAF250a protein. Recent studies have shown the loss of ARID1A expression in several types of tumors. We aimed to investigate the clinical and pathologic role of BAF250a in endometrial carcinoma. We examined the expression of BAF250a and its correlation with the expression of p53, estrogen receptor, progesterone receptor, glucocorticoid receptor, hypoxiainduciblefactor-1α, and vascular endothelial growth factor in normal and various malignant endometrial tissues. The expression of BAF250 was significantly down-regulated in endometrial carcinoma when compared with normal endometrial tissues. The loss of BAF250a expression was found in 25% of endometrial carcinoma samples but not in normal endometrial tissues, complex endometrial hyperplasia, and atypical endometrial hyperplasia samples. Subtypes of endometrial carcinoma, especially uterine endometrioid carcinoma and uterine clear cell carcinoma, had higher frequency of loss of BAF250a expression. In addition, the expression of BAF250a was positively correlated with estrogen receptor and negatively correlated with p53 in poorly differentiated endometrial adenocarcinoma. Moreover, the expression of BAF250a was significantly associated with the differentiation status of endometrial carcinoma but not associated with clinical stage, the depth of myometrial invasion, lymph node metastasis, and overall survival of patients with endometrial carcinoma. Our data showed that loss of BAF250a is frequently found in high-grade endometrioid and clear cell carcinomas but not in other types of endometrial carcinoma. The loss of BAF250a expression does not have prognostic value for endometrial carcinoma.

Fibroids and in-vitro fertilization: which comes first?

PubMed

Rackow, Beth W; Arici, Aydin

2005-06-01

There is no consensus about the impact of uterine fibroids on fertility. This review explores past and recent studies that investigated the effects of submucosal, intramural, and subserosal fibroids on in-vitro fertilization (IVF) outcomes. We discuss the importance of proper evaluation of the uterus and endometrial cavity, and current options for optimal fibroid management in patients desiring fertility. Several studies have reviewed the data on fibroids and infertility, further exploring this potential relationship. Two recent studies investigated reproductive outcomes before and after myomectomy, and IVF outcomes based on fibroid size and location. Both studies concluded that fibroids can impair reproductive outcomes. Several papers thoroughly reviewed medical and surgical management options for patients with fibroids and desired fertility. Although several medical therapies may reduce fibroid volume or decrease menorrhagia, myomectomy remains the standard of care for future fertility. Recent data identified an increased rate of pregnancy complications after uterine artery embolization compared with laparoscopic myomectomy. A new procedure, magnetic resonance imaging-guided focused ultrasound ablation, shows promise for the management of symptomatic fibroids, and possibly for the management of fibroids prior to pregnancy. As with embolization, more data are needed to evaluate postprocedure fertility and pregnancy outcomes. Fibroid location, followed by size, is the most important factor determining the impact of fibroids on IVF outcomes. Any distortion of the endometrial cavity seriously affects IVF outcomes, and myomectomy is indicated in this situation. Myomectomy should also be considered for patients with large fibroids, and for patients with unexplained unsuccessful IVF cycles.

Hysteroscopic Endometrial Resection Versus Laparoscopic Supracervical Hysterectomy for Abnormal Uterine Bleeding: Long-term Follow-up of a Randomized Trial.

PubMed

Zupi, Errico; Centini, Gabriele; Lazzeri, Lucia; Finco, Andrea; Exacoustos, Caterina; Afors, Karolina; Zullo, Fulvio; Petraglia, Felice

2015-01-01

To compare long-term efficacy of laparoscopic supracervical hysterectomy (LSH) and hysteroscopic endometrial ablation (HEA) in treating persistent abnormal uterine bleeding. Canadian Task Force II-2. University hospital. One hundred fifty-three women treated for abnormal uterine bleeding by LSH or HEA. Long-term follow-up assessment of reintervention rate and quality of life (QoL) using the Quality Metric's Health Survey Short Form 12. This study is the long-term follow-up of a randomized control trial conducted in 2003 comparing LSH and HEA in terms of reoperation rate and QoL. Starting from November 2010 all patients included in the first trial were invited to participate in this study and clinically evaluated through vaginal examination and transvaginal ultrasound. After a mean follow-up of 14.4 years, 29% of patients (20/71) treated with HEA underwent further surgery, whereas no patients after LSH had symptom recurrence. The reintervention rate was significantly higher in the HEA group (p < .0001), with a relative risk of 1.39 (95% confidence interval, 1.20-1.61). The assessment of QoL demonstrated a higher score, in both physical and mental components, in the LSH group (p < .0001). The lower reintervention rate and the better physical and mental health scores make LSH a more suitable procedure to treat recurrent abnormal uterine bleeding when compared with HEA. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

High-temperature thermal treatment of the uterus

NASA Astrophysics Data System (ADS)

Ryan, Thomas P.; Xiao, Jia Hua; Chung, Juh Yun

2003-06-01

More than 200,000 hysterectomies are performed annually in the US due to abnormal uterine bleeding from excessive menstrual flow. A minimally invasive procedure has been developed using thermal treatment combined with pressure to the endometrial lining of the uterus. Results from a 3-D finite element model will be shown, as well as experimental data. Good correlation was seen between simulations and experiments. The study found similar results then temperatures were increased and times for treatment were shortened.More than 200,000 hysterectomies are performed annually in the US due to abnormal uterine bleeding from excessive menstrual flow. A minimally invasive procedure has been developed using a balloon-based thermal treatment combined with pressure to the endometrial lining of the uterus. A 3D finite element model was set up to simulate the balloon ablation device in the human uterus as used in over 150,000 patients to date. Several additional simulations were made at higher temperatures to seek alternative combinations with higher temperature and shorter time intervals for the same depth of penetration, or deeper penetration at longer times and elevated temperatures. A temperature range of 87 to 150°C was explored. The Bioheat Equation was used in the simulations to predict temperature distributions in tissue. The Damage Integral was also used to characterize the location at depth of irreversible damage in the uterus. Treatment safety issues were also analyzed as the simulations showed the depth of penetration into the myometrium, towards the serosa.

Decreased endometrial HOXA10 expression associated with use of the copper intrauterine-device

PubMed Central

Tetrault, Amy M; Richman, Susan M; Fei, Xiaolan; Taylor, Hugh S

2009-01-01

Objective To characterize human endometrial HOXA10 expression in patients using copper intrauterine devices (IUD). Design Case-control study. Setting Academic medical center Patient(s) Women using copper IUD Interventions(s) Immunohistochemical analysis of endometrial HOXA10 expression in biopsies obtained from 24 women using copper Paraguard T380A as well as in biopsies obtained from 10 normal cycling women who were not using IUD or hormonal contraceptives. Main Outcome Measure(s) Endometrial HOXA10 expression. Result(s) Endometrial HOXA10 expression was markedly decreased in biopsies obtained from women using IUD contraceptive when compared to controls. The mean H score for endometrial stromal cell HOXA10 expression in biopsies obtained from women using Paraguard IUD was 0.21 compared to 2.2 in the control endometrial biopsies (P<0.001). Endometrial glandular expression of HOXA10 was absent in all IUD users. Conclusion(s) Decreased endometrial HOXA10 expression was apparent in women who use a copper IUD. Expression of HOXA10 is essential for endometrial receptivity. A novel mechanism of copper IUD action involves suppression of genes required for endometrial receptivity. The dramatic decrease of endometrial HOXA10 in response to IUD use may contribute to contraceptive efficacy. PMID:18930214

Comparison of 2-dimensional, 3-dimensional, and vascular ultrasonographic parameters for endometrial receptivity between 2 consecutive stimulated in vitro fertilization cycles.

PubMed

Ng, Ernest Hung Yu; Chan, Carina Chi Wai; Tang, Oi Shan; Ho, Pak Chung

2007-07-01

We compared the ultrasonographic parameters for endometrial receptivity between 2 consecutive in vitro fertilization (IVF) cycles in the same patients. Patients who had undergone 2 in vitro fertilization cycles between November 2002 and December 2004 were recruited. A 3-dimensional ultrasonographic examination with power Doppler imaging was performed on the day of oocyte retrieval to determine the endometrial thickness, endometrial pattern, pulsatility and resistive indices of uterine vessels, endometrial volume, vascularization index, flow index, and vascularization flow index of endometrial and subendometrial regions. Of 662 patients, 95 (14.4%) underwent 2 consecutive cycles using the same stimulation regimen during the study period. There were no significant differences in these ultrasonographic parameters between the first and second cycles. The intraclass correlation coefficient (ICC) for endometrial volume was significantly higher than that of other ultrasonographic parameters. The ICC for the endometrial thickness, uterine pulsatility index, and endometrial 3-dimensional power Doppler flow indices were similar. Ultrasonographic parameters for endometrial receptivity were comparable in the 2 consecutive stimulated cycles. The endometrial volume had the highest ICC among these ultrasonographic parameters and was most reproducible between 2 cycles.

Brain Metastases from Endometrial Carcinoma

PubMed Central

Piura, Ettie; Piura, Benjamin

2012-01-01

This paper will focus on knowledge related to brain metastases from endometrial carcinoma. To date, 115 cases were documented in the literature with an incidence of 0.6% among endometrial carcinoma patients. The endometrial carcinoma was usually an advanced-stage and high-grade tumor. In most patients (~90%), brain metastasis was detected after diagnosis of endometrial carcinoma with a median interval from diagnosis of endometrial carcinoma to diagnosis of brain metastases of 17 months. Brain metastasis from endometrial carcinoma was either an isolated disease limited to the brain only (~50%) or part of a disseminated disease involving also other parts of the body (~50%). Most often, brain metastasis from endometrial carcinoma affected the cerebrum (~75%) and was solitary (~60%). The median survival after diagnosis of brain metastases from endometrial carcinoma was 5 months; however, a significantly better survival was achieved with multimodal therapy including surgical resection or stereotactic radiosurgery followed by whole brain radiotherapy (WBRT) and/or chemotherapy compared to WBRT alone. It is suggested that brain imaging studies should be considered in the routine follow up of patients with endometrial carcinoma and that the search for a primary source in females with brain metastases of unknown primary should include endometrial biopsy. PMID:22523707

Endometrial neoplasia in reproductive-aged Thai women with polycystic ovary syndrome.

PubMed

Indhavivadhana, Suchada; Rattanachaiyanont, Manee; Wongwananuruk, Thanyarat; Techatraisak, Kitirat; Rayasawath, Nana; Dangrat, Chongdee

2018-05-09

To determine the risk of endometrial neoplasia in relation to endometrial thickness and to evaluate factors influencing endometrial thickness in reproductive-aged Thai women with polycystic ovary syndrome (PCOS). The present cross-sectional study was done at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, between October 1, 2010, and January 31, 2013. We recruited women (aged ≥18 years) with PCOS diagnosed according to the revised 2003 Rotterdam criteria. Data were collected for physical examinations, pelvic ultrasonography, hormonal profiles, and carbohydrate metabolic profiles. Endometrial tissue was obtained using a disposable endometrial-suctioning device. The final analysis included 122 women. Six (4.9%) patients had endometrial neoplasia. All six women had an endometrial thickness of 7 mm or more, representing a risk of 8.7% (6/69) in this group. The endometrial thickness was significantly but weakly associated with body mass index (r=0.227, P=0.012), 2-hour blood glucose (r=0.323, P=0.001), fasting glucose to insulin ratio (r=0.185, P=0.042), homeostatic model assessment of insulin resistance (r=0.183, P=0.044), and free testosterone (r=0.236, P=0.009). No categorical risk factors for an endometrial thickness of 7 mm or more were identified. Thai women with PCOS and a thick endometrium (≥7 mm) had an 8.7% risk of endometrial neoplasia. Invasive endometrial surveillance for the prevention of endometrial cancer is recommended in these women. © 2018 International Federation of Gynecology and Obstetrics.

A novel solution configuration on liquid-based endometrial cytology

PubMed Central

Wang, Qi; Han, Lu; Tuo, Xiaoqian; Hou, Huilian; Liu, Yu; Shi, Zan; Wang, Qing; Li, Yan; Sun, Chao; Xue, Xue

2018-01-01

Objective Early detection and diagnosis of endometrial carcinoma and precancerous change would undoubtedly become the most alluring part for researchers. With the emergence of endometrial brush samplers, a new upsurge in endometrial cytology is in the making. But endometrial specimens obtained by the endometrial brush samplers require special preservation solution. The objective of this study is to develop a new kind of endometrial-cell preservation solution and to test the availability compared with a patented liquid-based cell preservation solution. Methods In this controlled study, we had 5 endometrial cases collected with Li Brush from the First Affiliated Hospital of Xi'an Jiaotong University (09/2016 to 12/2016). The samples of each case were collected 2 times separately and perserved in different perservation solutions. One was a kind of novel endometrial cell preservation solution and the other was a kind of patented liquid-based cell (LBC) preservation solution. The endometrial cells were smeared on slides by using the ZP-C automated slide preparation system and stained with Papanicolaou stain. A semi-quantitative scoring system was used to analyze the quality of slides. Statistical analysis was performed using the Wilcoxon signed rank test on the SPSS program (SPSS 18.0). In all LBC preparations, endometrial cells from the novel endometrial cells preservation solution had more cell quantity, less red blood cell fragments, and the background was cleaner compared with control group. Although the novel endometrial-cell preservation solution showed cellularity and absence of blood and debris expressed by no statistically significant differences (p = 0.063 and 0.102 respectively). The preservation period of the two kinds of liquids was equivalent. Conclusions The novel endometrial-cell preservation solution is superior to the liquid-base cell preservation solution for cervical cells, with clear background, diagnostic cells and low cost. PMID:29401497

A Trial for Patients With Advanced/Recurrent Endometrial Cancer

ClinicalTrials.gov

2009-11-13

Neoplasms; Neoplasms by Site; Urogenital Neoplasms; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms; Cancer of Endometrium; Endometrial Cancer; Cancer of the Endometrium; Endometrium Cancer; Neoplasms, Endometrial

Endometrial thickness as a predictor of the reproductive outcomes in fresh and frozen embryo transfer cycles: A retrospective cohort study of 1512 IVF cycles with morphologically good-quality blastocyst.

PubMed

Zhang, Tao; Li, Zhou; Ren, Xinling; Huang, Bo; Zhu, Guijin; Yang, Wei; Jin, Lei

2018-01-01

To evaluate the relationship between endometrial thickness during fresh in vitro fertilization (IVF) cycles and the clinical outcomes of subsequent frozen embryo transfer (FET) cycles.FET cycles using at least one morphological good-quality blastocyst conducted between 2012 and 2013 at a university-based reproductive center were reviewed retrospectively. Endometrial ultrasonographic characteristics were recorded both on the oocyte retrieval day and on the day of progesterone supplementation in FET cycles. Clinical pregnancy rate, spontaneous abortion rate, and live birth rate were analyzed.One thousand five hundred twelve FET cycles was included. The results showed that significant difference in endometrial thickness on day of oocyte retrieval (P = .03) was observed between the live birth group (n = 844) and no live birth group (n = 668), while no significant difference in FET endometrial thickness was found (P = .261) between the live birth group and no live birth group. For endometrial thickness on oocyte retrieval day, clinical pregnancy rate ranged from 50.0% among patients with an endometrial thickness of ≤6 mm to 84.2% among patients with an endometrial thickness of >16 mm, with live birth rate from 33.3% to 63.2%. Multiple logistic regression analysis of factors related to live birth indicated endometrial thickness on oocyte retrieval day was associated with improved live birth rate (OR was 1.069, 95% CI: 1.011-1.130, P = .019), while FET endometrial thickness did not contribute significantly to pregnancy outcomes following FET cycles. The ROC curves revealed the cut-off points of endometrial thickness on oocyte retrieval day was 8.75 mm for live birth.Endometrial thickness during fresh IVF cycles was a better predictor of endometrial receptivity in subsequent FET cycles than FET cycle endometrial thickness. For those females with thin endometrium in fresh cycles, additional estradiol stimulation might be helpful for adequate endometrial development.

Endometrial thickness as a predictor of the reproductive outcomes in fresh and frozen embryo transfer cycles

PubMed Central

Zhang, Tao; Li, Zhou; Ren, Xinling; Huang, Bo; Zhu, Guijin; Yang, Wei; Jin, Lei

2018-01-01

Abstract To evaluate the relationship between endometrial thickness during fresh in vitro fertilization (IVF) cycles and the clinical outcomes of subsequent frozen embryo transfer (FET) cycles. FET cycles using at least one morphological good-quality blastocyst conducted between 2012 and 2013 at a university-based reproductive center were reviewed retrospectively. Endometrial ultrasonographic characteristics were recorded both on the oocyte retrieval day and on the day of progesterone supplementation in FET cycles. Clinical pregnancy rate, spontaneous abortion rate, and live birth rate were analyzed. One thousand five hundred twelve FET cycles was included. The results showed that significant difference in endometrial thickness on day of oocyte retrieval (P = .03) was observed between the live birth group (n = 844) and no live birth group (n = 668), while no significant difference in FET endometrial thickness was found (P = .261) between the live birth group and no live birth group. For endometrial thickness on oocyte retrieval day, clinical pregnancy rate ranged from 50.0% among patients with an endometrial thickness of ≤6 mm to 84.2% among patients with an endometrial thickness of >16 mm, with live birth rate from 33.3% to 63.2%. Multiple logistic regression analysis of factors related to live birth indicated endometrial thickness on oocyte retrieval day was associated with improved live birth rate (OR was 1.069, 95% CI: 1.011–1.130, P = .019), while FET endometrial thickness did not contribute significantly to pregnancy outcomes following FET cycles. The ROC curves revealed the cut-off points of endometrial thickness on oocyte retrieval day was 8.75 mm for live birth. Endometrial thickness during fresh IVF cycles was a better predictor of endometrial receptivity in subsequent FET cycles than FET cycle endometrial thickness. For those females with thin endometrium in fresh cycles, additional estradiol stimulation might be helpful for adequate endometrial development. PMID:29369190

Therapeutic Amenorrhea in Patients at Risk for Thrombocytopenia

PubMed Central

Martin-Johnston, Meredith K.; Okoji, Olanma Y.; Armstrong, Alicia

2016-01-01

To examine the need for and evaluate the method of menses suppression in women at risk for thrombocytopenia. A systematic review of the published literature in MEDLINE using the search terms thrombocytopenia, menorrhagia, therapeutic amenorrhea, progestin intrauterine device, combination oral contraceptive—extended and cyclic, gonadotropin releasing hormone agonist, danazol, and progestins. There are an increased number of reproductive age women at risk for thrombocytopenia who would benefit from menses suppression. A number of effective medical regimens are available. In patients who fail medical therapy, endometrial ablation appears to be effective in women with thrombocytopenia. As a result of the increased number of women at risk for thrombocytopenia, there is a need for therapeutic amenorrhea. The type of regimen selected depends upon the patients need for contraception and the ability to tolerate estrogen-containing medications. For women who fail medical therapy, there are surgical options, which are associated with less morbidity than hysterectomy. PMID:18492296

Small endometrial carcinoma 10 mm or less in diameter: clinicopathologic and histogenetic study of 131 cases for early detection and treatment

PubMed Central

Hasumi, Katsuhiko; Sugiyama, Yuko; Sakamoto, Kimihiko; Akiyama, Futoshi

2013-01-01

Natural history and clinicopathologic features of early endometrial carcinoma are not evident. Its knowledge is essential to make up strategies for prevention, early detection, and treatment of endometrial carcinoma. Especially it is important to know pathways of endometrial carcinogenesis and frequency of endometrial carcinomas arising from endometrial hyperplasia. Clinicopathologically 131 patients with endometrial carcinoma measuring ≤10 mm in diameter (“small endometrial carcinoma”) were studied to get useful information for early diagnosis, treatment, and histogenesis. The entire endometrium of surgically removed uterus was step-cut and examined. The patients were, on average, 5 years younger than the controls whose carcinomas measure >10 mm (P < 0.0001). Of the 131 patients, 20% were asymptomatic although only 5% of the controls were asymptomatic (P < 0.0001). Seventy-six percent had the carcinomas located in the upper third section of the uterine corpus. Macroscopically 44% of the tumors were flat and 56% were elevated. Incidence of nodal and ovarian metastases were <1%. Forty percent of “small endometrial carcinomas” were associated with endometrial hyperplasia and 60% were not. It is logical to believe that there are two pathways of endometrial carcinogenesis: carcinomas occurring from hyperplasia (40%) and carcinomas occurring from normal endometrium (60%). As hyperplasia-carcinoma sequence is not a main route, we cannot probably prevent carcinomas only by treatment of hyperplasia. Effort must be focused on detecting early de novo carcinomas. As most “small endometrial carcinomas” arise in the upper third of the corpus, careful endometrial sampling there is important for early detection. PMID:24403260

Fludeoxyglucose F 18 PET Scan, CT Scan, and Ferumoxtran-10 MRI Scan Before Chemotherapy and Radiation Therapy in Finding Lymph Node Metastasis in Patients With Locally Advanced Cervical Cancer or High-Risk Endometrial Cancer

ClinicalTrials.gov

2016-11-14

Cervical Adenocarcinoma; Cervical Adenosquamous Cell Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage IVA Cervical Cancer

Is postmenopausal endometrial fluid collection alone a risk factor for endometrial cancer?

PubMed

Yegin Akcay, Gulin Feykan; Tas, Emre Erdem; Yavuz, Ayse Filiz

2018-01-01

To determine the usefulness of single-layer, ultrasonographic measurement of endometrial fluid collection (EFC) volume to predict endometrial pathology in asymptomatic postmenopausal patients. One hundred fifty asymptomatic postmenopausal women were analysed retrospectively from January 2012 to December 2016. After patients with endometrial hyperplasia/neoplasia were included in Group-I, and those with insufficient tissue, endometrial atrophy, or endometritis were included in Group-II; Groups one and two were compared with respect to primary (correlations between endometrial thickness and EFC volume) and secondary (correlations between demographic characteristics and EFC volume) outcomes. There was no correlation between EFC volume and single-layer endometrial thickness ( P = 0.36). Likewise, demographic characteristics were not related to EFC ( P > 0.05). However, both EFC volume and single-layer endometrial thickness were thicker in Group-I compared to Group-II (4.8 ± 1.9 mm vs . 3.7 ± 2.5 mm; and 5.7 ± 9.4 mm vs . 2.7 ± 2.5 mm, respectively) ( P values were < 0.05). Although a cutoff value for endometrial thickness and EFC volume could not be recommended based on our study findings, it should be noted that 2% is a clinically significant rate of malignancy. Thus, postmenopausal patients with EFC should be evaluated for endometrial sampling.

Genetic Risk Score Mendelian Randomization Shows that Obesity Measured as Body Mass Index, but not Waist:Hip Ratio, Is Causal for Endometrial Cancer.

PubMed

Painter, Jodie N; O'Mara, Tracy A; Marquart, Louise; Webb, Penelope M; Attia, John; Medland, Sarah E; Cheng, Timothy; Dennis, Joe; Holliday, Elizabeth G; McEvoy, Mark; Scott, Rodney J; Ahmed, Shahana; Healey, Catherine S; Shah, Mitul; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley V; Beckmann, Matthias W; Ekici, Arif B; Fasching, Peter A; Hein, Alexander; Rübner, Matthias; Czene, Kamila; Darabi, Hatef; Hall, Per; Li, Jingmei; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Amant, Frederic; Annibali, Daniela; Depreeuw, Jeroen; Lambrechts, Diether; Neven, Patrick; Cunningham, Julie M; Dowdy, Sean C; Goode, Ellen L; Fridley, Brooke L; Winham, Stacey J; Njølstad, Tormund S; Salvesen, Helga B; Trovik, Jone; Werner, Henrica M J; Ashton, Katie A; Otton, Geoffrey; Proietto, Anthony; Mints, Miriam; Tham, Emma; Bolla, Manjeet K; Michailidou, Kyriaki; Wang, Qin; Tyrer, Jonathan P; Hopper, John L; Peto, Julian; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Pharoah, Paul D P; Tomlinson, Ian; Dunning, Alison M; Easton, Douglas F; Thompson, Deborah J; Spurdle, Amanda B

2016-11-01

The strongest known risk factor for endometrial cancer is obesity. To determine whether SNPs associated with increased body mass index (BMI) or waist-hip ratio (WHR) are associated with endometrial cancer risk, independent of measured BMI, we investigated relationships between 77 BMI and 47 WHR SNPs and endometrial cancer in 6,609 cases and 37,926 country-matched controls. Logistic regression analysis and fixed effects meta-analysis were used to test for associations between endometrial cancer risk and (i) individual BMI or WHR SNPs, (ii) a combined weighted genetic risk score (wGRS) for BMI or WHR. Causality of BMI for endometrial cancer was assessed using Mendelian randomization, with BMIwGRS as instrumental variable. The BMIwGRS was significantly associated with endometrial cancer risk (P = 3.4 × 10 -17 ). Scaling the effect of the BMIwGRS on endometrial cancer risk by its effect on BMI, the endometrial cancer OR per 5 kg/m 2 of genetically predicted BMI was 2.06 [95% confidence interval (CI), 1.89-2.21], larger than the observed effect of BMI on endometrial cancer risk (OR = 1.55; 95% CI, 1.44-1.68, per 5 kg/m 2 ). The association attenuated but remained significant after adjusting for BMI (OR = 1.22; 95% CI, 1.10-1.39; P = 5.3 × 10 -4 ). There was evidence of directional pleiotropy (P = 1.5 × 10 -4 ). BMI SNP rs2075650 was associated with endometrial cancer at study-wide significance (P < 4.0 × 10 -4 ), independent of BMI. Endometrial cancer was not significantly associated with individual WHR SNPs or the WHRwGRS. BMI, but not WHR, is causally associated with endometrial cancer risk, with evidence that some BMI-associated SNPs alter endometrial cancer risk via mechanisms other than measurable BMI. The causal association between BMI SNPs and endometrial cancer has possible implications for endometrial cancer risk modeling. Cancer Epidemiol Biomarkers Prev; 25(11); 1503-10. ©2016 AACR. ©2016 American Association for Cancer Research.

Paclitaxel, Carboplatin, and Bevacizumab or Paclitaxel, Carboplatin, and Temsirolimus or Ixabepilone, Carboplatin, and Bevacizumab in Treating Patients With Stage III, Stage IV, or Recurrent Endometrial Cancer

ClinicalTrials.gov

2018-01-29

Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

Small endometrial carcinoma 10 mm or less in diameter: clinicopathologic and histogenetic study of 131 cases for early detection and treatment.

PubMed

Hasumi, Katsuhiko; Sugiyama, Yuko; Sakamoto, Kimihiko; Akiyama, Futoshi

2013-12-01

Natural history and clinicopathologic features of early endometrial carcinoma are not evident. Its knowledge is essential to make up strategies for prevention, early detection, and treatment of endometrial carcinoma. Especially it is important to know pathways of endometrial carcinogenesis and frequency of endometrial carcinomas arising from endometrial hyperplasia. Clinicopathologically 131 patients with endometrial carcinoma measuring ≤10 mm in diameter ("small endometrial carcinoma") were studied to get useful information for early diagnosis, treatment, and histogenesis. The entire endometrium of surgically removed uterus was step-cut and examined. The patients were, on average, 5 years younger than the controls whose carcinomas measure >10 mm (P < 0.0001). Of the 131 patients, 20% were asymptomatic although only 5% of the controls were asymptomatic (P < 0.0001). Seventy-six percent had the carcinomas located in the upper third section of the uterine corpus. Macroscopically 44% of the tumors were flat and 56% were elevated. Incidence of nodal and ovarian metastases were <1%. Forty percent of "small endometrial carcinomas" were associated with endometrial hyperplasia and 60% were not. It is logical to believe that there are two pathways of endometrial carcinogenesis: carcinomas occurring from hyperplasia (40%) and carcinomas occurring from normal endometrium (60%). As hyperplasia-carcinoma sequence is not a main route, we cannot probably prevent carcinomas only by treatment of hyperplasia. Effort must be focused on detecting early de novo carcinomas. As most "small endometrial carcinomas" arise in the upper third of the corpus, careful endometrial sampling there is important for early detection. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Fibulin-4 is associated with prognosis of endometrial cancer patients and inhibits cancer cell invasion and metastasis via Wnt/β-catenin signaling pathway

PubMed Central

Wang, Tiantian; Wang, Mei; Fang, Shuang; Wang, Qiang; Fang, Rui; Chen, Jie

2017-01-01

Fibulin-4, an extracellular glycoprotein, which plays significant roles in elastic fiber assembly, is correlated to the progression of some cancers. However, the role of fibulin-4 in endometrial cancer cell invasion and metastasis remains unexplored. In our study, fibulin-4 expression was assessed by immunohistochemistry (IHC) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in normal endometrial tissues and endometrial carcinoma tissues. Using single cell cloning, strongly, and weakly, invasive subclones were derived from KLE and Ishikawa endometrial carcinoma cell lines. RT-qPCR, western blotting, and immunocytochemistry (ICC) were used to assess mRNA and protein expressions of fibulin-4 in primary cultured endometrial cells, 4 types of endometrial cancer cell lines, and the different invasive subclones. Using lentivirus transfection, fibulin-4 shRNA and pLVX-fibulin-4 were constructed and used to infect the strongly and weakly invasive subclones. The effects of fibulin-4 on the biological characteristics of endometrial carcinoma cells were detected by cell functional assays in vitro and in vivo. Using Wnt signaling pathway inhibitor XAV-939 and activator LiCl, we detected the role of fibulin-4 in the Wnt/β-catenin pathway and the relationship with epithelial to mesenchymal transition (EMT). Fibulin-4 was decreased in endometrial carcinoma tissues, and loss of fibulin-4 expression was significantly related with poor differentiation, lymph node metastasis, and poor prognosis of endometrial carcinoma. Fibulin-4 significantly inhibited endometrial carcinoma cell proliferation, invasion, metastasis, and EMT through the Wnt/β-catenin pathway. Fibulin-4 has the ability to suppress endometrial cancer progression. These results can contribute to the development of a new potential therapeutic target for patients with endometrial carcinoma. PMID:28177909

Expression of immune checkpoint molecules in endometrial carcinoma

PubMed Central

LIU, JIA; LIU, YULING; WANG, WULIANG; WANG, CHENYANG; CHE, YANHONG

2015-01-01

The main obstacle in the development of an effective tumor vaccine is the inherent ability of tumors to evade immune responses. Tumors often use common immune mechanisms and regulators to evade the immune system. The present study aimed to analyze the expression levels of indoleamine 2,3-dioxygenase (IDO), programmed death-ligand (PD-L) 1, PD-L2, B7-H4, galectin-1 and galectin-3 in tissue samples from patients with endometrial carcinoma, in order to detect the immunosuppressive environment of endometrial carcinomas. The levels of IDO, PD-L1, PD-L2 and B7-H4 were analyzed by immunohistochemical methods, and the levels of galectin-1 and galectin-3 in tumor lysates were determined using ELISA. PD-L2 was expressed at low levels in the majority of tumor samples. IDO expression was detected in 38, 63 and 43% of primary endometrial carcinoma, recurrent endometrial carcinoma, and metastatic endometrial carcinoma specimens, respectively. Positive expression rates for PD-L1 were 83% in primary endometrial carcinoma, 68% in recurrent endometrial carcinoma, and 100% in metastatic endometrial carcinoma, whereas B7-H4 expression was detected in 100% of both primary endometrial carcinoma and recurrent endometrial carcinoma samples, and in 96% of metastatic endometrial carcinoma specimens. The expression levels of galectin-1 and galectin-3 were not significantly different between the normal and tumor specimens. The results of the present study suggest that the interaction between PD-1/PD-L1 and B7-H4 may be a potential target for immune intervention in the treatment of endometrial carcinoma. Furthermore, the results may provide the basis for immunosuppressant therapy in the treatment of patients with uterine cancer. PMID:26640578

Stem Cell-Like Differentiation Potentials of Endometrial Side Population Cells as Revealed by a Newly Developed In Vivo Endometrial Stem Cell Assay

PubMed Central

Miyazaki, Kaoru; Maruyama, Tetsuo; Masuda, Hirotaka; Yamasaki, Akiko; Uchida, Sayaka; Oda, Hideyuki; Uchida, Hiroshi; Yoshimura, Yasunori

2012-01-01

Background Endometrial stem/progenitor cells contribute to the cyclical regeneration of human endometrium throughout a woman's reproductive life. Although the candidate cell populations have been extensively studied, no consensus exists regarding which endometrial population represents the stem/progenitor cell fraction in terms of in vivo stem cell activity. We have previously reported that human endometrial side population cells (ESP), but not endometrial main population cells (EMP), exhibit stem cell-like properties, including in vivo reconstitution of endometrium-like tissues when xenotransplanted into immunodeficient mice. The reconstitution efficiency, however, was low presumably because ESP cells alone could not provide a sufficient microenvironment (niche) to support their stem cell activity. The objective of this study was to establish a novel in vivo endometrial stem cell assay employing cell tracking and tissue reconstitution systems and to examine the stem cell properties of ESP through use of this assay. Methodology/Principal Findings ESP and EMP cells isolated from whole endometrial cells were infected with lentivirus to express tandem Tomato (TdTom), a red fluorescent protein. They were mixed with unlabeled whole endometrial cells and then transplanted under the kidney capsule of ovariectomized immunodeficient mice. These mice were treated with estradiol and progesterone for eight weeks and nephrectomized. All of the grafts reconstituted endometrium-like tissues under the kidney capsules. Immunofluorescence revealed that TdTom-positive cells were significantly more abundant in the glandular, stromal, and endothelial cells of the reconstituted endometrium in mice transplanted with TdTom-labeled ESP cells than those with TdTom-labeled EMP cells. Conclusions/Significance We have established a novel in vivo endometrial stem cell assay in which multi-potential differentiation can be identified through cell tracking during in vivo endometrial tissue reconstitution. Using this assay, we demonstrated that ESP cells differentiated into multiple endometrial lineages in the niche provided by whole endometrial cells, indicating that ESP cells are genuine endometrial stem/progenitor cells. PMID:23226538

ZEB1 overexpression associated with E-cadherin and microRNA-200 downregulation is characteristic of undifferentiated endometrial carcinoma.

PubMed

Romero-Pérez, Laura; López-García, M Ángeles; Díaz-Martín, Juan; Biscuola, Michele; Castilla, M Ángeles; Tafe, Laura J; Garg, Karuna; Oliva, Esther; Matias-Guiu, Xavier; Soslow, Robert A; Palacios, José

2013-11-01

Undifferentiated endometrial carcinomas are very aggressive high-grade endometrial carcinomas that are frequently under-recognized. This study aimed to analyze the molecular alterations underlying the development of these endometrial carcinomas, focusing on those related to dedifferentiation. We assessed a series of 120 tumors: 57 grade 1 and 2 endometrioid endometrial carcinomas, 15 grade 3 endometrioid endometrial carcinomas, 27 endometrial serous carcinomas, and 21 undifferentiated endometrial carcinomas. We found a high frequency of DNA mismatch repair deficiency (38%) and moderate rate of p53 overexpression (∼33%) in undifferentiated carcinomas. In contrast to the characteristic endometrioid phenotype, there was a dramatic downregulation of E-cadherin expression in the undifferentiated subtype. Quantitative methylation studies dismissed CDH1 promoter hypermethylation as the mechanism responsible for this change in gene expression, while immunohistochemistry revealed that the E-cadherin repressor ZEB1 was frequently overexpressed (62%) in undifferentiated endometrial carcinomas. This finding was accompanied by a sharp downregulation in the expression of the miR-200 family of microRNAs, well-known targets of ZEB1. Furthermore, there was enhanced expression of epithelial-to-mesenchymal transition markers in undifferentiated endometrial carcinomas, such as N-cadherin, cytoplasmic p120, and osteonectin. In addition, HMGA2, a regulator of epithelial-to-mesenchymal transition that is expressed in aggressive endometrial tumors, such as endometrial serous carcinomas and carcinosarcomas, was expressed in >20% of undifferentiated carcinomas. These results suggest that ZEB1 overexpression, associated with E-cadherin and miR-200s downregulation, and the expression of mesenchymal markers might enhance the metastatic potential of undifferentiated endometrial carcinomas, leading to a poor prognosis. In addition, our observations suggest that the immnohistochemical analysis of E-cadherin and ZEB1 can aid in the differential diagnosis of the more agressive undifferentiated endometrial carcinomas from grade 3 endometrioid carcinomas.

DJ-1 is a reliable serum biomarker for discriminating high-risk endometrial cancer.

PubMed

Di Cello, Annalisa; Di Sanzo, Maddalena; Perrone, Francesca Marta; Santamaria, Gianluca; Rania, Erika; Angotti, Elvira; Venturella, Roberta; Mancuso, Serafina; Zullo, Fulvio; Cuda, Giovanni; Costanzo, Francesco

2017-06-01

New reliable approaches to stratify patients with endometrial cancer into risk categories are highly needed. We have recently demonstrated that DJ-1 is overexpressed in endometrial cancer, showing significantly higher levels both in serum and tissue of patients with high-risk endometrial cancer compared with low-risk endometrial cancer. In this experimental study, we further extended our observation, evaluating the role of DJ-1 as an accurate serum biomarker for high-risk endometrial cancer. A total of 101 endometrial cancer patients and 44 healthy subjects were prospectively recruited. DJ-1 serum levels were evaluated comparing cases and controls and, among endometrial cancer patients, between high- and low-risk patients. The results demonstrate that DJ-1 levels are significantly higher in cases versus controls and in high- versus low-risk patients. The receiver operating characteristic curve analysis shows that DJ-1 has a very good diagnostic accuracy in discriminating endometrial cancer patients versus controls and an excellent accuracy in distinguishing, among endometrial cancer patients, low- from high-risk cases. DJ-1 sensitivity and specificity are the highest when high- and low-risk patients are compared, reaching the value of 95% and 99%, respectively. Moreover, DJ-1 serum levels seem to be correlated with worsening of the endometrial cancer grade and histotype, making it a reliable tool in the preoperative decision-making process.

Ultrasound in assisted reproduction: a call to fill the endometrial gap.

PubMed

Hershko-Klement, Anat; Tepper, Ronnie

2016-06-01

Ultrasound offers essential details and an overall view of the anatomic features of the reproductive organs, as well as physiologic assessment. There is still a great gap, however, in our understanding and interpretation of endometrial sonographic findings. Endometrial thickness, growth, and sonographic patterns have been repeatedly tested and compared with pregnancy rates in IVF cycles, yielding conflicting results. Generally, the data accrued so far suggest refraining from clinical decisions based solely on endometrial thickness. The three-layer ultrasound pattern reflects normal follicular/proliferative dynamics, and its presence in the pre-hCG period was reported to carry a better outcome: Significantly higher clinical pregnancy rates were found in patients with this pattern on the day of hCG administration among IVF cohorts. Subendometrial contractility (endometrial "waves") offers a tool that can be used in cases of repeated implantation failure in patients reporting cramps around the planned time of embryo transfer, or as a reassuring modality to assess uterine quiescence during preparations for embryo transfer. We support the creation of an integrated endometrial score incorporating conservative endometrial measurements, endometrial-myometrial junction studies, and endometrial contractility, as well as new concepts that remain to be tested, such as endometrial surface area. Such scores may enable us to improve the effectiveness of endometrial ultrasound imaging in the clinical setting. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian

MedlinePlus

... Bar Home Current Issue Past Issues 6 Common Cancers - Gynecologic Cancers Cervical, Endometrial, and Ovarian Past Issues / Spring 2007 ... of this page please turn Javascript on. Gynecologic Cancers Cervical, Endometrial, and Ovarian NCI estimates that endometrial, ...

Endometrial metastasis of colorectal cancer with coincident endometrial adenocarcinoma.

PubMed

Colling, Richard; Lopes, Tito; Das, Nagiindra; Mathew, Joe

2010-11-05

Metastasis to the uterine corpus is uncommon and secondary colorectal tumours of the endometrium are rare. We describe a uterine tumour with components of both primary endometrial and metastatic colorectal carcinomata. In this case, a 72-year-old obese woman presented with a 2-week history of postmenopausal bleeding per vaginum and weight loss. She had an abdominoperineal resection 3 years previously for a Dukes stage B rectal carcinoma. A transvaginal ultrasonography showed a thickened endometrium. Histology immunophenotyping showed a CK7+, CK20+, CA125- and CEA+ colorectal metastasis (a profile consistent with her previous cancer) associated with a primary CK7+, CK20-, CA125+ and CEA- endometroid endometrial adenocarcinoma. We conclude this represents endometrial metastasis of colorectal carcinoma with coincident primary endometrial adenocarcinoma. We speculate as to whether the endometrial carcinoma arose de novo or was induced by the colorectal metastasis, or whether the primary endometrial tumour provided a fertile site for the colorectal metastasis.

Evaluation of a levonorgestrel-releasing intrauterine system for treating endometrial hyperplasia in patients with polycystic ovary syndrome.

PubMed

Lin, Min; Xu, XiaoWen; Wang, Yi; Hu, Yue; Zhao, Yu

2014-01-01

To evaluate the use of a levonorgestrel-releasing intrauterine system (LNG-IUS) for treating endometrial hyperplasia in patients with polycystic ovary syndrome (PCOS). LNG-IUSs were inserted in 60 PCOS patients with simple (40 cases), irregular (12 cases), or complex (8 cases) endometrial hyperplasia. Follow-ups were performed at 3, 6, 12, and 24 months after insertion. At each time point, changes in menstruation, hemoglobin level, and endometrial thickness and pathology were recorded. Menstrual changes were assessed with the Pictorial Blood Assessment Chart. Hemoglobin levels were measured by the Blood Routine Test. Endometrial thickness was determined by transvaginal ultrasound. Endometrial pathology was defined as simple, irregular, or complex endometrial hyperplasia by a pathologist after curettage. Outcomes at each time point were compared to baseline (pre-insertion) measurements by Student's t test or ANOVA (for multiple comparisons) with the post hoc Dunnett's test. Differences with a p < 0.05 were considered statistically significant. At all time points after LNG-IUS insertion and in all patients, menstrual blood loss was decreased and hemoglobin level was increased significantly compared to pre-insertion levels. The endometrial thickness was significantly reduced in all groups after 12 months. Most patients showed transformation of the endometrial pathology, with complete disappearance of simple and irregular cases of endometrial hyperplasia and a decreased number of complex endometrial hyperplasia cases. LNG-IUS is an effective, safe, nonsurgical, and atraumatic approach with few side effects for the treatment of endometrial hyperplasia in patients with PCOS. © 2014 S. Karger AG, Basel.

Prospective multicenter randomized intermediate biomarker study of oral contraceptive versus depo-provera for prevention of endometrial cancer in women with Lynch syndrome.

PubMed

Lu, Karen H; Loose, David S; Yates, Melinda S; Nogueras-Gonzalez, Graciela M; Munsell, Mark F; Chen, Lee-May; Lynch, Henry; Cornelison, Terri; Boyd-Rogers, Stephanie; Rubin, Mary; Daniels, Molly S; Conrad, Peggy; Milbourne, Andrea; Gershenson, David M; Broaddus, Russell R

2013-08-01

Women with Lynch syndrome have a 40% to 60% lifetime risk for developing endometrial cancer, a cancer associated with estrogen imbalance. The molecular basis for endometrial-specific tumorigenesis is unclear. Progestins inhibit estrogen-driven proliferation, and epidemiologic studies have shown that progestin-containing oral contraceptives (OCP) reduce the risk of endometrial cancer by 50% in women at general population risk. It is unknown whether they are effective in women with Lynch syndrome. Asymptomatic women ages 25 to 50 with Lynch syndrome were randomized to receive the progestin compounds Depo-Provera (depo-MPA) or OCP for three months. An endometrial biopsy and transvaginal ultrasound were conducted before and after treatment. Endometrial proliferation was evaluated as the primary endpoint. Histology and a panel of surrogate endpoint biomarkers were evaluated for each endometrial biopsy as secondary endpoints. A total of 51 women were enrolled, and 46 completed treatment. Two of the 51 women had complex hyperplasia with atypia at the baseline endometrial biopsy and were excluded from the study. Overall, both depo-MPA and OCP induced a dramatic decrease in endometrial epithelial proliferation and microscopic changes in the endometrium characteristic of progestin action. Transvaginal ultrasound measurement of endometrial stripe was not a useful measure of endometrial response or baseline hyperplasia. These results show that women with Lynch syndrome do show an endometrial response to short-term exogenous progestins, suggesting that OCP and depo-MPA may be reasonable chemopreventive agents in this high-risk patient population.

Prospective, Multi-center Randomized Intermediate Biomarker Study of Oral Contraceptive vs. Depo-Provera for Prevention of Endometrial Cancer in Women with Lynch Syndrome

PubMed Central

Lu, Karen H.; Loose, David S.; Yates, Melinda S.; Nogueras-Gonzalez, Graciela M.; Munsell, Mark F.; Chen, Lee-may; Lynch, Henry; Cornelison, Terri; Boyd-Rogers, Stephanie; Rubin, Mary; Daniels, Molly S.; Conrad, Peggy; Milbourne, Andrea; Gershenson, David M.; Broaddus, Russell R.

2013-01-01

Women with Lynch syndrome have a 40–60% lifetime risk for developing endometrial cancer, a cancer associated with estrogen imbalance. The molecular basis for endometrial-specific tumorigenesis is unclear. Progestins inhibit estrogen-driven proliferation, and epidemiologic studies have demonstrated that progestin-containing oral contraceptives (OCP) reduce the risk of endometrial cancer by 50% in women at general population risk. It is unknown if they are effective in women with Lynch syndrome. Asymptomatic women age 25–50 with Lynch syndrome were randomized to receive the progestin compounds depo-Provera (depoMPA) or OCP for three months. An endometrial biopsy and transvaginal ultrasound were performed before and after treatment. Endometrial proliferation was evaluated as the primary endpoint. Histology and a panel of surrogate endpoint biomarkers were evaluated for each endometrial biopsy as secondary endpoints. A total of 51 women were enrolled, and 46 completed treatment. Two of the 51 women had complex hyperplasia with atypia at the baseline endometrial biopsy and were excluded from the study. Overall, both depoMPA and OCP induced a dramatic decrease in endometrial epithelial proliferation and microscopic changes in the endometrium characteristic of progestin action. Transvaginal ultrasound measurement of endometrial stripe was not a useful measure of endometrial response or baseline hyperplasia. These results demonstrate that women with Lynch syndrome do show an endometrial response to short term exogenous progestins, suggesting that OCP and depoMPA may be reasonable chemopreventive agents in this high-risk patient population. PMID:23639481

Relations of Platelet Indices with Endometrial Hyperplasia and Endometrial Cancer.

PubMed

Karateke, Atilla; Kaplanoglu, Mustafa; Baloglu, Ali

2015-01-01

Platelets are blood elements thought to play a role in the immune system and therefore tumor development and metastasis. Platelet activation parameters such as mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) can be easily evaluated with the whole blood count and have been studied as markers of systemic inflammatory responses in various cancer types. Our aim in this study was to evaluate the correlation between endometrial pathologies and MPV, PDW and PCT. A total of 194 patients who presented to our clinic with abnormal vaginal bleeding were included in our study. The patients were divided into 3 groups (endometrial hyperplasia, endometrial cancer, control) according to their pathology results. The groups were compared for MPV, PDW, and PCT values obtained from the blood samples taken on endometrial biopsy day. The endometrial cancer patients were the oldest group (p=0.04). There was no significant difference between the three groups in terms of white blood cell count (WBC), platelet count (PC), and hemoglobin (Hb) level. The highest MPV (p<0.001), PDW (p=0.002), and PCT (p<0.001) levels were in the endometrial cancer group, and the lowest levels were in the control group. The easy evaluation of platelet parameters in patients who are suspected of having endometrial pathology is a significant advantage. We found MPV, PDW, and PCT to be correlated with the severity of endometrial pathology with the highest values in endometrial cancer. Studies to be conducted together with different laboratory parameters will further help evaluate the diagnosis and severity of endometrial cancer and precursor lesions.

Cigarette smoking and endometrial carcinoma risk: the role of effect modification and tumor heterogeneity

PubMed Central

Yang, Hannah P.; Gierach, Gretchen L.; Park, Yikyung; Brinton, Louise A.

2014-01-01

Purpose The inverse relationship between cigarette smoking and endometrial carcinoma risk is well established. We examined effect modification of this relationship and associations with tumor characteristics in the National Institutes of Health–AARP Diet and Health Study. Methods We examined the association between cigarette smoking and endometrial carcinoma risk among 110,304 women. During 1,029,041 person years of follow-up, we identified 1,476 incident endometrial carcinoma cases. Multivariable Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95 % confidence intervals (CIs) for the association between smoking status, years since smoking cessation, and endometrial carcinoma risk overall and within strata of endometrial carcinoma risk factors. Effect modification was assessed using likelihood ratio test statistics. Smoking associations by histologic subtype/grade and stage at diagnosis were also evaluated. Results Reduced endometrial carcinoma risk was evident among former (RR 0.89, 95 % CI 0.80, 1.00) and current (RR 0.65, 95 % CI 0.55, 0.78) smokers compared with never smokers. Smoking cessation 1–4 years prior to baseline was significantly associated with endometrial carcinoma risk (RR 0.65, 95 % CI 0.48, 0.89), while cessation ≥10 years before baseline was not. The association between smoking and endometrial carcinoma risk was not significantly modified by any endometrial carcinoma risk factor, nor did we observe major differences in risk associations by tumor characteristics. Conclusion The cigarette smoking–endometrial carcinoma risk relationship was consistent within strata of important endometrial carcinoma risk factors and by clinically relevant tumor characteristics. PMID:24487725

A randomised trial comparing endometrial resection and abdominal hysterectomy for the treatment of menorrhagia.

PubMed Central

Gannon, M J; Holt, E M; Fairbank, J; Fitzgerald, M; Milne, M A; Crystal, A M; Greenhalf, J O

1991-01-01

OBJECTIVE--To determine the advantages and disadvantages of endometrial resection and abdominal hysterectomy for the surgical treatment of women with menorrhagia. DESIGN--Randomised study of two treatment groups with a minimum follow up of nine months. SETTING--Royal Berkshire Hospital, Reading. SUBJECTS--51 of 78 menorrhagic women without pelvic pathology who were on the waiting list for abdominal hysterectomy. TREATMENT--Endometrial resection or abdominal hysterectomy (according to randomisation). Endometrial resections were performed by an experienced hysteroscopic surgeon; hysterectomies were performed by two other gynaecological surgeons. MAIN OUTCOME MEASURES--Length of operating time, hospitalisation, recovery; cost of surgery; short term results of endometrial resection. RESULTS--Operating time was shorter for endometrial resection (median 30 (range 20-47) minutes) than for hysterectomy (50 (39-74) minutes). The hospital stay for endometrial resection (median 1 (range 1-3) days) was less than for hysterectomy (7 (5-12) days). Recovery after endometrial resection (median 16 (range 5-62) days) was shorter than after hysterectomy (58 (11-125) days). The cost was 407 pounds for endometrial resection and 1270 pounds for abdominal hysterectomy. Four women (16%) who did not have an acceptable improvement in symptoms after endometrial resection had repeat resections. No woman has required hysterectomy during a mean follow up of one year. CONCLUSION--For women with menorrhagia who have no pelvic pathology endometrial resection is a useful alternative to abdominal hysterectomy, with many short term benefits. Larger numbers and a longer follow up are needed to estimate the incidence of complications and the long term efficacy of endometrial resection. PMID:1760601

Implications of telomeres and telomerase in endometrial pathology

PubMed Central

Hapangama, D.K.; Kamal, A.; Saretzki, G.

2017-01-01

Abstract BACKGROUND Eukaryotic chromosomal ends are linear and are protected by nucleoprotein complexes known as telomeres. The complex structural anatomy and the diverse functions of telomeres as well as the unique reverse transcriptase enzyme, telomerase that maintains telomeres are under intensive scientific scrutiny. Both are involved in many human diseases including cancer, but also in ageing and chronic disease such as diabetes. Their intricate involvement in many cellular processes and pathways is being dynamically deciphered in many organs including the endometrium. This review summarizes our current knowledge on the topic of telomeres and telomerase and their potential role in providing plausible explanations for endometrial aberrations related to common gynaecological pathologies. OBJECTIVE AND RATIONALE This review outlines the recent major findings in telomere and telomerase functions in the context of endometrial biology. It highlights the contemporary discoveries in hormonal regulation, normal endometrial regeneration, stem cells and common gynaecological diseases such as endometriosis, infertility, recurrent reproductive failure and endometrial cancer (EC). SEARCH METHODS The authors carried out systematic PubMed (Medline) and Ovid searches using the key words: telomerase, telomeres, telomere length, human telomerase reverse transcriptase, telomeric RNA component, with endometrium, hormonal regulation, endometrial stem/progenitor cells, endometrial regeneration, endometriosis, recurrent miscarriage, infertility, endometrial hyperplasia, EC and uterine cancer. Publications used in this review date from 1995 until 31st June 2016. OUTCOMES The human endometrium is a unique somatic organ, which displays dynamic telomerase activity (TA) related to the menstrual cycle. Telomerase is implicated in almost all endometrial pathologies and appears to be crucial to endometrial stem cells. In particular, it is vital for normal endometrial regeneration, providing a distinct route to formulate possible curative, non-hormonal therapies to treat chronic endometrial conditions. Furthermore, our current understanding of telomere maintenance in EC is incomplete. Data derived from other malignancies on the role of telomerase in carcinogenesis cannot be extrapolated to EC because unlike in other cancers, TA is already present in proliferating healthy endometrial cells. WIDER IMPLICATIONS Since telomerase is pivotal to endometrial regeneration, further studies elucidating the role of telomeres, telomerase, their associated proteins and their regulation in normal endometrial regeneration as well as their role in endometrial pathologies are essential. This approach may allow future development of novel treatment strategies that are not only non-hormonal but also potentially curative. PMID:27979878

The endometrium in breast cancer patients on tamoxifen.

PubMed

Dallenbach-Hellweg, G; Schmidt, D; Hellberg, P; Bourne, T; Kreuzwieser, E; Dören, M; Rydh, W; Rudenstam, G; Granberg, S

2000-04-01

We restudied histologically and immunohistochemically 17 endometrial carcinomas, 2 malignant mixed tumors and 180 endometria with benign changes during or after tamoxifen therapy. The carcinomas were subtyped according to the 1994 WHO-classification. Endometrial biopsies were taken only if the endometrial thickness was > 8 mm sonographically, when a polyp was seen, or for postmenopausal bleeding. About half of the endometrial specimens showed simple or cystic atrophy, 55-76% had cystic-atrophic polyps or regressive hyperplasia. Depending upon the dose of tamoxifen, 7-19% (30 mg) to 27-36% (20 mg) showed moderate glandular proliferation. 20-33% had foci of mucinous, clear cell or serous-papillary metaplasia. 68-70% revealed diffuse extensive fibrosis of the endometrial stroma. None of 11 patients biopsied before starting tamoxifen therapy had advanced endometrial glandular proliferation in the second endometrial biopsy after tamoxifen treatment. None of the 19 endometrial neoplasms after tamoxifen therapy was of the endometrioid type: 11 were mucinous adenocarcinomas, 4 clear cell carcinomas, 2 serous-papillary carcinomas, one carcinosarcoma and one malignant Mullerian mixed tumor. The reasons for discrepancies between suspicious sonograms and endometrial atrophy are discussed.

Management of abnormal uterine bleeding in low- and high-resource settings: consideration of cultural issues.

PubMed

Haththotuwa, Rohana; Goonewardene, Malik; Desai, Shyam; Senanayake, Lakshman; Tank, Jaydeep; Fraser, Ian S

2011-09-01

In non industrialized countries the incidence of heavy menstrual bleeding (HMB) appears to be similar to that of industrialized countries, although data is scanty. In low-resource settings, women with abnormal uterine bleeding (AUB) often delay seeking medical care because of cultural beliefs that a heavy red menstrual bleed is healthy. Efforts to modify cultural issues are being considered. A detailed history and a meticulous examination are the important foundations of a definitive diagnosis and management in low-resource settings but are subject to time constraints and skill levels of the small numbers of health professionals. Women's subjective assessment of blood loss should be combined, if possible, with a colorimetric hemoglobin assessment, if full blood count is not possible. Outpatient endometrial sampling, transvaginal sonography, and hysteroscopy are available in some non industrialized countries but not in the lowest resource settings. After exclusion of serious underlying pathology, hematinics should be commenced and antifibrinolytic or nonsteroidal anti-inflammatory drugs considered during menses to control the bleeding. Intrauterine or oral progestogens or the combined oral contraceptive are often the most cost-effective long-term medical treatments. When medical treatment is inappropriate or has failed, the surgical options available most often are myomectomy or hysterectomy. Hysteroscopic endometrial resection or newer endometrial ablation procedures are available in some centers. If hysterectomy is indicated the vaginal route is the most appropriate in most low-resource settings. In low-resource settings, lack of resources of all types can lead to empirical treatments or reliance on the unproven therapies of traditional healers. The shortage of human resources is often compounded by a limited availability of operative time. Governments and specialist medical organizations have rarely included attention to AUB and HMB in their health programs. Local guidelines and attention to training of doctors, midwives, and traditional health workers are critical for prevention and improvement in management of HMB and its consequences for iron deficiency anemia and postpartum hemorrhage, the major killer of young women in developing countries. © Thieme Medical Publishers.

Correlation between transvaginal ultrasound measured endometrial thickness and histopathological findings in Turkish women with abnormal uterine bleeding.

PubMed

Ozer, Alev; Ozer, Serdar; Kanat-Pektas, Mine

2016-05-01

The present study aims to determine how transvaginal ultrasonography and histopathological examination findings are correlated in a cohort of premenopausal and postmenopausal Turkish women with abnormal uterine bleeding. This is a retrospective review of 350 Turkish women who underwent transvaginal ultrasonography and suction curettage as a result of abnormal uterine bleeding. Sonographic appearance of the endometrium was normal in 244 patients (69.7%), while homogeneous thickening was detected in 47 patients (13.4%) and cystic thickening in 21 patients (6.0%). A sonographic diagnosis of endometrial polyp was made in 38 patients (10.9%). Histopathological analysis of endometrial samplings revealed proliferative endometrium (36%), secretory endometrium (24.6%), decidualization (10.9%), endometrial polyp (8.3%), endometritis (6.8%), endometrial hyperplasia (4.6%), irregular shedding (3.7%), atrophic endometrium (3.1%), endometrial cancer (1.1%) and placental retention (0.9%). The sonographic and histopathological findings correlated significantly (χ(2) = 122 768, P = 0.001; r = 0.215, P = 0.001). Approximately 51% of the women with homogeneous endometrial thickening had proliferative endometrium. Only 44.7% of the women with ultrasonographically visualized endometrial polyps had histopathologically diagnosed endometrial polyps. Nearly 57% of the women with cystic endometrial thickening had proliferative endometrium. If there is no facility for hysteroscopy or hysteroscopy-guided endometrial biopsy for women with abnormal uterine bleeding, transvaginal ultrasonography findings can be efficiently used to make a preliminary diagnosis and, thus, notify the pathologists. © 2016 Japan Society of Obstetrics and Gynecology.

Biological effects of plasma rich in growth factors (PRGF) on human endometrial fibroblasts.

PubMed

Anitua, Eduardo; de la Fuente, María; Ferrando, Marcos; Quintana, Fernando; Larreategui, Zaloa; Matorras, Roberto; Orive, Gorka

2016-11-01

To evaluate the biological outcomes of plasma rich in growth factors (PRGF) on human endometrial fibroblasts in culture. PRGF was obtained from three healthy donors and human endometrial fibroblasts (HEF) were isolated from endometrial specimens from five healthy women. The effects of PRGF on cell proliferation and migration, secretion of vascular endothelial growth factor (VEGF), procollagen type I and hyaluronic acid (HA) and contractility of isolated and cultured human endometrial fibroblasts (HEF) were analyzed. Statistical analysis was performed in order to compare the effects of PRGF with respect to control situation (T-test or Mann-Whitney U-test). We report a significantly elevated human endometrial fibroblast proliferation and migration after treatment with PRGF. In addition, stimulation of HEF with PRGF induced an increased expression of the angiogenic factor VEGF and favored the endometrial matrix remodeling by the secretion of procollagen type I and HA and endometrial regeneration by elevating the contractility of HEF. These results were obtained for all PRGF donors and each endometrial cell line. The myriad of growth factors contained in PRGF promoted HEF proliferation, migration and synthesis of paracrine molecules apart from increasing their contractility potential. These preliminary results suggest that PRGF improves the biological activity of HEF in vitro, enhancing the regulation of several cellular processes implied in endometrial regeneration. This innovative treatment deserves further investigation for its potential in "in vivo" endometrial development and especially in human embryo implantation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Short Course Vaginal Cuff Brachytherapy in Treating Patients With Stage I-II Endometrial Cancer

ClinicalTrials.gov

2018-04-17

Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage I Uterine Corpus Cancer; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Uterine Corpus Carcinosarcoma; Uterine Corpus Sarcoma

Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Bevacizumab in Treating Patients With Stage IV Melanoma That Cannot Be Removed by Surgery or Gynecological Cancers

ClinicalTrials.gov

2018-02-05

Cervical Adenosarcoma; Cervical Adenosquamous Carcinoma; Cervical Carcinosarcoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Endometrial Clear Cell Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Mixed Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Squamous Cell Carcinoma; Endometrial Transitional Cell Carcinoma; Endometrial Undifferentiated Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Epithelial Tumor; Malignant Peritoneal Neoplasm; Ovarian Carcinosarcoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IV Skin Melanoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma; Uterine Corpus Carcinosarcoma

Endometrial adenocarcinoma in a 13-year-old girl.

PubMed

Kim, Sung Mee; Shin, So Jin; Bae, Jin Gon; Kwon, Kun Young; Rhee, Jeong Ho

2016-03-01

Endometrial cancer is the third most common gynecologic cancer in the Korea and occurs mainly in menopausal women. Although it can develop in young premenopausal women cancer as well, an attack in the adolescent girl is very rare. A 13-year-old girl visited gynecology department with the complaint of abnormal uterine bleeding. An endometrial biopsy revealed FIGO (International Federation of Gynecology and Obstetrics) grade II endometrial adenocarcinoma. In the treatment of endometrial cancer, conservative management should be considered if the patient is nulliparous or wants the fertility preservation. Therefore, we decided to perform a hormonal therapy and a follow-up endometrial biopsy after progestin administration for eight months revealed no residual tumor. We report a case of endometrial cancer occurred in a 13-year-old girl with a brief review of the literature.

Sampling in Atypical Endometrial Hyperplasia: Which Method Results in the Lowest Underestimation of Endometrial Cancer? A Systematic Review and Meta-analysis.

PubMed

Bourdel, Nicolas; Chauvet, Pauline; Tognazza, Enrica; Pereira, Bruno; Botchorishvili, Revaz; Canis, Michel

2016-01-01

Our objective was to identify the most accurate method of endometrial sampling for the diagnosis of complex atypical hyperplasia (CAH), and the related risk of underestimation of endometrial cancer. We conducted a systematic literature search in PubMed and EMBASE (January 1999-September 2013) to identify all registered articles on this subject. Studies were selected with a 2-step method. First, titles and abstracts were analyzed by 2 reviewers, and 69 relevant articles were selected for full reading. Then, the full articles were evaluated to determine whether full inclusion criteria were met. We selected 27 studies, taking into consideration the comparison between histology of endometrial hyperplasia obtained by diagnostic tests of interest (uterine curettage, hysteroscopically guided biopsy, or hysteroscopic endometrial resection) and subsequent results of hysterectomy. Analysis of the studies reviewed focused on 1106 patients with a preoperative diagnosis of atypical endometrial hyperplasia. The mean risk of finding endometrial cancer at hysterectomy after atypical endometrial hyperplasia diagnosed by uterine curettage was 32.7% (95% confidence interval [CI], 26.2-39.9), with a risk of 45.3% (95% CI, 32.8-58.5) after hysteroscopically guided biopsy and 5.8% (95% CI, 0.8-31.7) after hysteroscopic resection. In total, the risk of underestimation of endometrial cancer reaches a very high rate in patients with CAH using the classic method of evaluation (i.e., uterine curettage or hysteroscopically guided biopsy). This rate of underdiagnosed endometrial cancer leads to the risk of inappropriate surgical procedures (31.7% of tubal conservation in the data available and no abdominal exploration in 24.6% of the cases). Hysteroscopic resection seems to reduce the risk of underdiagnosed endometrial cancer. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

The effect of fertility stress on endometrial and subendometrial blood flow among infertile women.

PubMed

Dong, Yuezhi; Cai, Yanna; Zhang, Yu; Xing, Yurong; Sun, Yingpu

2017-03-04

To investigate the effect of fertility stress on endometrial and subendometrial blood flow among infertile women. This case-control study was conducted in The First Affiliated Hospital of Zhengzhou University. The fertility problem inventory (FPI) was adopted to evaluate fertility stress. Three-dimensional power Doppler ultrasonography (3D PD-US) was performed during the proliferative phase of the menstrual cycle (days 5-11) to measure endometrial thickness, pattern, endometrial and subendometrial volume (V), the vascularization index (VI), the flow index (FI) and the vascularization-FI (VFI) index. Then, 300 infertile women were separated into two groups (high-score group and low-score group) based on total FPI scores and 80 healthy women were selected as controls. No differences were found among all three groups with regard to general characteristics, endometrial thickness, pattern, endometrial and subendometrial V, VI and VFI. The endometrial and subendometrial FIs associated with different stress levels significantly differed among the three groups (F = 33.95, P < 0.001; F = 44.79, P < 0.001, respectively). The endometrial and subendometrial FIs in the control group were significantly higher than those in the high-score group and low-score groups. The endometrial and subendometrial FIs in the low-score group were significantly higher than those in the high-score group. The total FPI score was closely related to the endometrial and subendometrial FIs (r = -0.304, P < 0.001; r = -0.407, P < 0.001, respectively). Fertility stress was associated with endometrial and subendometrial flow index. Whether fertility stress might affect pregnancy outcome by reducing endometrial and subendometrial blood flow requires further research.

Discovery and validation of methylation markers for endometrial cancer

PubMed Central

Wentzensen, Nicolas; Bakkum-Gamez, Jamie N.; Killian, J. Keith; Sampson, Joshua; Guido, Richard; Glass, Andrew; Adams, Lisa; Luhn, Patricia; Brinton, Louise A.; Rush, Brenda; d’Ambrosio, Lori; Gunja, Munira; Yang, Hannah P.; Garcia-Closas, Montserrat; Lacey, James V.; Lissowska, Jolanta; Podratz, Karl; Meltzer, Paul; Shridhar, Viji; Sherman, Mark E.

2014-01-01

The prognosis of endometrial cancer is strongly associated with stage at diagnosis, suggesting that early detection may reduce mortality. Women who are diagnosed with endometrial carcinoma often have a lengthy history of vaginal bleeding, which offers an opportunity for early diagnosis and curative treatment. We performed DNA methylation profiling on population-based endometrial cancers to identify early detection biomarkers and replicated top candidates in two independent studies. We compared DNA methylation values of 1500 probes representing 807 genes in 148 population-based endometrial carcinoma samples and 23 benign endometrial tissues. Markers were replicated in another set of 69 carcinomas and 40 benign tissues profiled on the same platform. Further replication was conducted in The Cancer Genome Atlas and in prospectively collected endometrial brushings from women with and without endometrial carcinomas. We identified 114 CpG sites showing methylation differences with p-values of ≤10−7 between endometrial carcinoma and normal endometrium. Eight genes (ADCYAP1, ASCL2, HS3ST2, HTR1B, MME, NPY, and SOX1) were selected for further replication. Age-adjusted odds ratios for endometrial cancer ranged from 3.44 (95%-CI: 1.33–8.91) for ASCL2 to 18.61 (95%-CI: 5.50–62.97) for HTR1B. An area under the curve (AUC) of 0.93 was achieved for discriminating carcinoma from benign endometrium. Replication in The Cancer Genome Atlas and in endometrial brushings from an independent study confirmed the candidate markers. This study demonstrates that methylation markers may be used to evaluate women with abnormal vaginal bleeding to distinguish women with endometrial carcinoma from the majority of women without malignancy. PMID:24623538

Family history and risk of endometrial cancer: a systematic review and meta-analysis.

PubMed

Win, Aung Ko; Reece, Jeanette C; Ryan, Shae

2015-01-01

To obtain precise estimates of endometrial cancer risk associated with a family history of endometrial cancer or cancers at other sites. For the systematic review, we used PubMed to search for all relevant studies on family history and endometrial cancer that were published before December 2013. Medical Subject Heading terms "endometrial neoplasm" and "uterine neoplasm" were used in combination with one of the key phrases "family history," "first-degree," "familial risk," "aggregation," or "relatedness." Studies were included if they were case-control or cohort studies that investigated the association between a family history of cancer specified to site and endometrial cancer. Studies were excluded if they were review or editorial articles or not translated into English or did not define family history clearly or used spouses as control participants. We included 16 studies containing 3,871 women as cases and 49,475 women as controls from 10 case-control studies and 33,510 women as cases from six cohort studies. We conducted meta-analyses to estimate the pooled relative risk (95% confidence interval [CI]) of endometrial cancer associated with a first-degree family history of endometrial, colorectal, breast, ovarian, and cervical cancer to be: 1.82 (1.65-1.98), 1.17 (1.03-1.31), 0.96 (0.88-1.04), 1.13 (0.85-1.41), and 1.19 (0.83-1.55), respectively. We estimated cumulative risk of endometrial cancer to age 70 years to be 3.1% (95% CI 2.8-3.4) for women with a first-degree relative with endometrial cancer and the population-attributable risk to be 3.5% (95% CI 2.8-4.2). Women with a first-degree family history of endometrial cancer or colorectal cancer have a higher risk of developing endometrial cancer than those without a family history. This study is likely to be of clinical relevance to inform women of their risk of endometrial cancer.

Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 and Temsirolimus in Treating Patients With Advanced Solid Tumors

ClinicalTrials.gov

2014-05-29

Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Recurrent Renal Cell Cancer; Stage III Endometrial Carcinoma; Stage III Renal Cell Cancer; Stage IV Endometrial Carcinoma; Stage IV Renal Cell Cancer; Unspecified Adult Solid Tumor, Protocol Specific

[Establishment of mouse endometrial injury model by electrocoagulation].

PubMed

Hu, Xiaoxiao; Lin, Xiaona; Jiang, Yinshen; Shi, Libing; Wang, Jieyu; Zhao, Lijuan; Zhang, Songying

2014-12-23

To establish the murine model of moderate endometrial injury. Electrocoagulation was applied to induce endometrial injury of ICR mice with 0.5 watts power while contralateral uterine cavity acted as control without electrocoagulation. The endometrial histomorphology was observed in 7 days later by microscopy and fetal number of each lateral uterus assessed at 17.5 days after pregnancy. At 7 days post-electrocoagulation, the average endometrial thickness of operating side was significantly thinner than that of control side (1.14 ± 0.08 vs 1.88 ± 0.15 mm, P < 0.05). The density of endometrial glands of operating side was significantly lower than that of control side (20 ± 2 vs 32 ± 3 per 100x field, P < 0.05). After pregnancy, the average number of embryos at operating side decreased by 63.1% compared with control (3 ± 2 vs 8 ± 2, P < 0.01). The established model of endometrial electrocoagulation injury shows morphologic changes and decreased fertile ability. It has potential uses for animal studies of endometrial injury treatment.

Human Endometrial CD98 Is Essential for Blastocyst Adhesion

PubMed Central

Domínguez, Francisco; Simón, Carlos; Quiñonero, Alicia; Ramírez, Miguel Ángel; González-Muñoz, Elena; Burghardt, Hans; Cervero, Ana; Martínez, Sebastián; Pellicer, Antonio; Palacín, Manuel; Sánchez-Madrid, Francisco; Yáñez-Mó, María

2010-01-01

Background Understanding the molecular basis of embryonic implantation is of great clinical and biological relevance. Little is currently known about the adhesion receptors that determine endometrial receptivity for embryonic implantation in humans. Methods and Principal Findings Using two human endometrial cell lines characterized by low and high receptivity, we identified the membrane receptor CD98 as a novel molecule selectively and significantly associated with the receptive phenotype. In human endometrial samples, CD98 was the only molecule studied whose expression was restricted to the implantation window in human endometrial tissue. CD98 expression was restricted to the apical surface and included in tetraspanin-enriched microdomains of primary endometrial epithelial cells, as demonstrated by the biochemical association between CD98 and tetraspanin CD9. CD98 expression was induced in vitro by treatment of primary endometrial epithelial cells with human chorionic gonadotropin, 17-β-estradiol, LIF or EGF. Endometrial overexpression of CD98 or tetraspanin CD9 greatly enhanced mouse blastocyst adhesion, while their siRNA-mediated depletion reduced the blastocyst adhesion rate. Conclusions These results indicate that CD98, a component of tetraspanin-enriched microdomains, appears to be an important determinant of human endometrial receptivity during the implantation window. PMID:20976164

Role of DNA Methylation and Epigenetic Silencing of HAND2 in Endometrial Cancer Development

PubMed Central

Hayward, Jane D.; Kannan, Athilakshmi; Mould, Tim; West, James; Zikan, Michal; Cibula, David; Fiegl, Heidi; Lee, Shih-Han; Wik, Elisabeth; Hadwin, Richard; Arora, Rupali; Lemech, Charlotte; Turunen, Henna; Pakarinen, Päivi; Jacobs, Ian J.; Salvesen, Helga B.; Bagchi, Milan K.; Bagchi, Indrani C.; Widschwendter, Martin

2013-01-01

Background Endometrial cancer incidence is continuing to rise in the wake of the current ageing and obesity epidemics. Much of the risk for endometrial cancer development is influenced by the environment and lifestyle. Accumulating evidence suggests that the epigenome serves as the interface between the genome and the environment and that hypermethylation of stem cell polycomb group target genes is an epigenetic hallmark of cancer. The objective of this study was to determine the functional role of epigenetic factors in endometrial cancer development. Methods and Findings Epigenome-wide methylation analysis of >27,000 CpG sites in endometrial cancer tissue samples (n = 64) and control samples (n = 23) revealed that HAND2 (a gene encoding a transcription factor expressed in the endometrial stroma) is one of the most commonly hypermethylated and silenced genes in endometrial cancer. A novel integrative epigenome-transcriptome-interactome analysis further revealed that HAND2 is the hub of the most highly ranked differential methylation hotspot in endometrial cancer. These findings were validated using candidate gene methylation analysis in multiple clinical sample sets of tissue samples from a total of 272 additional women. Increased HAND2 methylation was a feature of premalignant endometrial lesions and was seen to parallel a decrease in RNA and protein levels. Furthermore, women with high endometrial HAND2 methylation in their premalignant lesions were less likely to respond to progesterone treatment. HAND2 methylation analysis of endometrial secretions collected using high vaginal swabs taken from women with postmenopausal bleeding specifically identified those patients with early stage endometrial cancer with both high sensitivity and high specificity (receiver operating characteristics area under the curve = 0.91 for stage 1A and 0.97 for higher than stage 1A). Finally, mice harbouring a Hand2 knock-out specifically in their endometrium were shown to develop precancerous endometrial lesions with increasing age, and these lesions also demonstrated a lack of PTEN expression. Conclusions HAND2 methylation is a common and crucial molecular alteration in endometrial cancer that could potentially be employed as a biomarker for early detection of endometrial cancer and as a predictor of treatment response. The true clinical utility of HAND2 DNA methylation, however, requires further validation in prospective studies. Please see later in the article for the Editors' Summary PMID:24265601

Cardiovascular disease is the leading cause of death among endometrial cancer patients.

PubMed

Ward, Kristy K; Shah, Nina R; Saenz, Cheryl C; McHale, Michael T; Alvarez, Edwin A; Plaxe, Steven C

2012-08-01

To evaluate the causes of death among women with endometrial cancer. SEER registries from 1973-1988 were queried to perform a retrospective cohort study of women with invasive epithelial endometrial cancer. Causes of death were compared according to grade and stage. 33,232 women with incident cases of endometrial cancer had died at the time of last follow up. Overall, women were most likely to die from cardiovascular disease (35.9%, 95% CI 35.3-36.3%), followed by other causes, other malignancies, and endometrial cancer. Women with low grade localized cancer were most likely to die of cardiovascular disease, while women with high grade advanced cancer were least likely to die of cardiovascular disease and most likely to die of endometrial cancer. For the entire population, risk of death from cardiovascular causes surpasses the risk of death from endometrial cancer 5 years after diagnosis. Higher risk of cardiac death among endometrial cancer patients likely reflects the high probability of curative cancer treatment and the prevalence of cardiac disease and risk factors. As the probability of dying of endometrial cancer decreases with time, the probability of dying of cardiovascular disease increases. Interventions and investigations aimed at addressing risk factors for cardiovascular disease may have the greatest potential to improve survival for women diagnosed with endometrial cancer and should feature prominently in treatment and survivorship plans. Copyright © 2012 Elsevier Inc. All rights reserved.

Epidemiology of Endometrial Carcinoma: Etiologic Importance of Hormonal and Metabolic Influences.

PubMed

Felix, Ashley S; Yang, Hannah P; Bell, Daphne W; Sherman, Mark E

2017-01-01

Endometrial carcinoma is the most common gynecologic cancer in developed nations, and the annual incidence is projected to increase, secondary to the high prevalence of obesity, a strong endometrial carcinoma risk factor. Although endometrial carcinomas are etiologically, biologically, and clinically diverse, hormonal and metabolic mechanisms are particularly strongly implicated in the pathogenesis of endometrioid carcinoma, the numerically predominant subtype. The centrality of hormonal and metabolic disturbances in the pathogenesis of endometrial carcinoma, combined with its slow development from well-characterized precursors in most cases, offers a substantial opportunity to reduce endometrial carcinoma mortality through early detection, lifestyle modification, and chemoprevention. In this chapter, we review the epidemiology of endometrial carcinoma, emphasizing theories that link risk factors for these tumors to hormonal and metabolic mechanisms. Future translational research opportunities related to prevention are discussed.

Surgical Management of Endometrial Polyps in Infertile Women: A Comprehensive Review

PubMed Central

Petrini, Allison C.; Lekovich, Jovana P.; Elias, Rony T.; Spandorfer, Steven D.

2015-01-01

Endometrial polyps are benign localized lesions of the endometrium, which are commonly seen in women of reproductive age. Observational studies have suggested a detrimental effect of endometrial polyps on fertility. The natural course of endometrial polyps remains unclear. Expectant management of small and asymptomatic polyps is reasonable in many cases. However, surgical resection of endometrial polyps is recommended in infertile patients prior to treatment in order to increase natural conception or assisted reproductive pregnancy rates. There is mixed evidence regarding the resection of newly diagnosed endometrial polyps during ovarian stimulation to improve the outcomes of fresh in vitro fertilization cycles. Hysteroscopy polypectomy remains the gold standard for surgical treatment. Evidence regarding the cost and efficacy of different methods for hysteroscopic resection of endometrial polyps in the office and outpatient surgical settings has begun to emerge. PMID:26301260

Evaluation of the benefit and use of the new terminology in endometrial cytology reporting system.

PubMed

Shinagawa, Akiko; Kurokawa, Tetsuji; Yamamoto, Makoto; Onuma, Toshimichi; Tsuyoshi, Hideaki; Chino, Yoko; Iwasaki, Kazumi; Mori, Masaki; Imamura, Yoshiaki; Yoshio, Yoshida

2018-04-01

The introduction and establishment of a new classification system for endometrial cytology, the "New Terminology in Endometrial Cytology (NTEMC) system," which is based on the Bethesda System for uterine cervical cytology, has recently been reported. However, the clinical management for new categories in the NTEMC system, particularly atypical endometrial cells (ATEC), has not been clarified. The objective of the present study is to determine how the ATEC category should be treated and whether the introduction of the system has decreased the number of unnecessary endometrial biopsies. Fifty-nine cases were diagnosed as "suspicious positive" according to the three-tier reporting (TTR) system, which was adopted in Japan. The specimens were re-evaluated according to the NTEMC system. Thirty-seven of the 59 patients underwent endometrial biopsy. We correlated the pathological diagnosis with the NTEMC system category. The 59 cases were classified according to the NTEMC system as follows: 36 cases were classified as ATEC of undetermined significance (ATEC-US), 21 cases were classified as ATEC for which atypical endometrial hyperplasia or worse cannot be excluded (ATEC-A), and 2 cases were classified as endometrial hyperplasia. The ratio of atypical endometrial hyperplasia or malignancy in ATEC-US category was significantly lower than that in ATEC-A category. Fifteen cases in ATEC-US category did not show atypical endometrial hyperplasia lesions or malignancy after 3 months. These data suggest that patients with ATEC-US results can be followed up for at least three months, and the introduction of the NTEMC system decreased the number of unnecessary endometrial biopsies. © 2018 Wiley Periodicals, Inc.

Exercise training prevents endometrial hyperplasia and biomarkers for endometrial cancer in rat model of type 1 diabetes.

PubMed

Al-Jarrah, Muhammed; Matalka, Ismail; Aseri, Hasan Al; Mohtaseb, Alia; Smirnova, Irina V; Novikova, Lesya; Stehno-Bittel, Lisa; Alkhateeb, Ahed

2010-10-11

Endometrial cancer is one of the most common types of gynecologic cancers. The ability of exercise to reduce the risk of endometrial cancer in women with type 2 diabetes has been established, but no studies have examined this link in type 1 diabetes.A randomized, controlled animal study was designed using a standard rat model of type 1 diabetes. The goal of this study was to investigate the ability of exercise to prevent increased levels of endometrial cancer biomarkers, estrogen receptor (ERα) and p16, and endometrial hyperplasia associated with diabetes. FORTY FEMALE RATS WERE RANDOMIZED INTO FOUR GROUPS: sedentary control, exercise control, sedentary or exercised diabetic. Diabetes was induced by alloxan injection. A 4-week treadmill training program was initiated with the development of diabetes. Endometrial tissues were evaluated for hyperplasia and ERα and p16 levels and subcellular localization using microscopy. Severe diabetes lead to hyperplasia in the endometrial tissue in 70% of sedentary diabetic rats. Exercise-trained diabetic rats and the non-diabetic rats displayed no hyperplasia. The expression of ERα increased significantly (p < 0.02) while the expression level of p16 decreased significantly (p < 0.04) in the diabetic sedentary group compared to the non-diabetic groups. Exercise training led to a reversal in the percentage of p16 and ERα positive cells in diabetic rats. Severe diabetes leads to hyperplasia of the endometrial tissue and increased ERα levels and decreased p16 levels in rats, which can be prevented with aerobic exercise. Diabetes; Estrogen receptor alpha; P16; Endometrial hyperplasia; Endometrial cancer; Exercise.

Immunohistochemical Study of ER, PR, Ki67 and p53 in Endometrial Hyperplasias and Endometrial Carcinomas

PubMed Central

Masjeed, Nayar Musfera Abdul; Joshi, Avinash R; Kulkarni, Maithili Mandar; Pandya, Nidhi

2017-01-01

Introduction Endometrial carcinoma is the second most common gynecologic malignancy in the developing countries. Endometrial Hyperplasia (EH) is a precursor to Endometrioid Adenocarcinoma (EMAC). A 23% of Atypical Hyperplasias (AEH) progress to EMAC. Aim This study was undertaken to analyse ER, PR, p53 and Ki67 in EH and endometrial carcinomas and attempt correlation with clinical and histopathological findings. Materials and Methods The present study was conducted over a period of seven years. A manual tissue array technique was employed for cases subjected to IHC. Analysis of the expression of IHC markers (ER, PR, p53, Ki67) in EH and endometrial carcinoma was attempted. Results were subjected to statistical analysis. The results were considered to be significant when the p-value <0.05. Results A total of 85 cases of EH and 28 cases of endometrial carcinoma were included in the study. EH (75.22%) was more common than endometrial carcinoma (24.78%). Among 28 cases of endometrial carcinomas, EMAC was most common (78.57%) followed by Clear Cell Carcinoma (CCC) (14.28%), and Uterine Serous Carcinoma (USC) (7.14%). ER and PR expression decreased as lesion progressed from EH to EMAC. ER and PR expression was negative in USC and CCC. The p53 expression and mean Ki67 labelling index increased as the severity of lesion increased from EH to endometrial carcinoma. Conclusion The ER, PR, p53, Ki67 IHC markers may be included in every case of endometrial carcinoma to understand the tumour biological behavior which in turn could help individual treatment strategies. PMID:28969139

Converging endometrial and ovarian tumorigenesis in Lynch syndrome: Shared origin of synchronous carcinomas.

PubMed

Niskakoski, Anni; Pasanen, Annukka; Porkka, Noora; Eldfors, Samuli; Lassus, Heini; Renkonen-Sinisalo, Laura; Kaur, Sippy; Mecklin, Jukka-Pekka; Bützow, Ralf; Peltomäki, Päivi

2018-04-28

The diagnosis of carcinoma in both the uterus and the ovary simultaneously is not uncommon and raises the question of synchronous primaries vs. metastatic disease. Targeted sequencing of sporadic synchronous endometrial and ovarian carcinomas has shown that such tumors are clonally related and thus represent metastatic disease from one site to the other. Our purpose was to investigate whether or not the same applies to Lynch syndrome (LS), in which synchronous cancers of the gynecological tract are twice as frequent as in sporadic cases, reflecting inherited defects in DNA mismatch repair (MMR). MMR gene mutation carriers with endometrial or ovarian carcinoma or endometrial hyperplasia were identified from a nationwide registry. Endometrial (n = 35) and ovarian carcinomas (n = 23), including 13 synchronous carcinoma pairs, were collected as well as endometrial hyperplasias (n = 56) and normal endometria (n = 99) from a surveillance program over two decades. All samples were studied for MMR status, ARID1A and L1CAM protein expression and tumor suppressor gene promoter methylation, and synchronous carcinomas additionally for somatic mutation profiles of 578 cancer-relevant genes. Synchronous carcinomas were molecularly concordant in all cases. Prior or concurrent complex (but not simple) endometrial hyperplasias showed a high degree of concordance with endometrial or ovarian carcinoma as the endpoint lesion. Our investigation suggests shared origins for synchronous endometrial and ovarian carcinomas in LS, in analogy to sporadic cases. The similar degrees of concordance between complex hyperplasias and endometrial vs. ovarian carcinoma highlight converging pathways for endometrial and ovarian tumorigenesis overall. Copyright © 2018. Published by Elsevier Inc.

Immunohistochemical Study of ER, PR, Ki67 and p53 in Endometrial Hyperplasias and Endometrial Carcinomas.

PubMed

Masjeed, Nayar Musfera Abdul; Khandeparkar, Siddhi Gaurish Sinai; Joshi, Avinash R; Kulkarni, Maithili Mandar; Pandya, Nidhi

2017-08-01

Endometrial carcinoma is the second most common gynecologic malignancy in the developing countries. Endometrial Hyperplasia (EH) is a precursor to Endometrioid Adenocarcinoma (EMAC). A 23% of Atypical Hyperplasias (AEH) progress to EMAC. This study was undertaken to analyse ER, PR, p53 and Ki67 in EH and endometrial carcinomas and attempt correlation with clinical and histopathological findings. The present study was conducted over a period of seven years. A manual tissue array technique was employed for cases subjected to IHC. Analysis of the expression of IHC markers (ER, PR, p53, Ki67) in EH and endometrial carcinoma was attempted. Results were subjected to statistical analysis. The results were considered to be significant when the p-value <0.05. A total of 85 cases of EH and 28 cases of endometrial carcinoma were included in the study. EH (75.22%) was more common than endometrial carcinoma (24.78%). Among 28 cases of endometrial carcinomas, EMAC was most common (78.57%) followed by Clear Cell Carcinoma (CCC) (14.28%), and Uterine Serous Carcinoma (USC) (7.14%). ER and PR expression decreased as lesion progressed from EH to EMAC. ER and PR expression was negative in USC and CCC. The p53 expression and mean Ki67 labelling index increased as the severity of lesion increased from EH to endometrial carcinoma. The ER, PR, p53, Ki67 IHC markers may be included in every case of endometrial carcinoma to understand the tumour biological behavior which in turn could help individual treatment strategies.

EF5 in Finding Oxygen in Tumor Cells of Patients Who Are Undergoing Surgery or Biopsy for Cervical, Endometrial, or Ovarian Epithelial Cancer

ClinicalTrials.gov

2013-01-15

Primary Peritoneal Cavity Cancer; Stage I Endometrial Carcinoma; Stage I Ovarian Epithelial Cancer; Stage IA Cervical Cancer; Stage IB Cervical Cancer; Stage II Endometrial Carcinoma; Stage II Ovarian Epithelial Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Endometrial Carcinoma; Stage III Ovarian Epithelial Cancer; Stage IV Endometrial Carcinoma; Stage IV Ovarian Epithelial Cancer; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer

Paclitaxel and Carboplatin With or Without Metformin Hydrochloride in Treating Patients With Stage III, IV, or Recurrent Endometrial Cancer

ClinicalTrials.gov

2018-03-07

Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Recurrent Uterine Corpus Carcinoma; Stage III Uterine Corpus Cancer AJCC v7; Stage IIIA Uterine Corpus Cancer AJCC v7; Stage IIIB Uterine Corpus Cancer AJCC v7; Stage IIIC Uterine Corpus Cancer AJCC v7; Stage IV Uterine Corpus Cancer AJCC v7; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7

[Immunomorphologic features of epithelial-stromal relationships at hyperplasia and endometrial carcinoma].

PubMed

Bantysh, B B; Paukov, v S; Kogan, E A

2012-01-01

The results of a immunomorphologic comprehensive study of epithelial-stromal relationships in the uterus hyperplasia and endometrial cancer suggest that the suppressor gene of cancer (PTEN) plays a key role in the process of neoplastic transformation of endometrial hyperplasia and adenocarcinoma development. For the first time the existence of two highly differentiated endometrial adenocarcinoma immunophenotype were detected The first one is a PTEN-negative endometrial aedenocarcinoma, characterized by an almost complete inhibition of tumor suppressor gene PTEN in the epithelium of the glands and stromal cell of the tumor The second type is a PTEN-positive endometrial adenocarcinoma, in which epithelial and stromal tumor suppressor gene PTEN activity has retained Based on these results we have formulated a hypothesis about the different types of endometrial hyperplasia morphogenesis and its possible transfer to cervical cancer associated with features of tumor suppressor gene PTEN.

Study of endometrial thickness by ultrasonography in regular and irregular menstrual cycles.

PubMed

Shinde, Charushila D; Patil, Pankaj G; Katti, Karuna; Geetha, K N

2013-10-01

Endometrium is the mucosal layer of uterus. Throughout the reproductive age endometrium undergoes cyclical changes during each lunar month to prepare the uterus for implantation. Endometrium proliferates and regenerates during menstrual cycle. The most common cause of abnormal vaginal bleeding during a woman's reproductive years is dysfunctional uterine bleeding. Aim of this study was to compare endometrial thickness in regular and irregular menstrual cycles. A total of 111 patients with regular and irregular menstrual bleeding were selected. Age, duration of menstrual cycle, detailed menstrual history, endometrial thickness, difference in endometrial thickness before and after treatment were recorded. Endometrial thickness was recorded by ultrasonography. In patients with abnormal uterine bleeding, if endometrial thickness was less than 8mm first medical line of treatment was advised. If endometrial thickness was greater than 8mm, line of treatment depended on age and pattern of bleeding.

Increased expression of resistin in ectopic endometrial tissue of women with endometriosis.

PubMed

Oh, Yoon Kyung; Ha, Young Ran; Yi, Kyong Wook; Park, Hyun Tae; Shin, Jung-Ho; Kim, Tak; Hur, Jun-Young

2017-11-01

Inflammation is a key process in the establishment and progression of endometriosis. Resistin, an adipocytokine, has biological properties linked to immunologic functions, but its role in endometriosis is unclear. Resistin gene expression was examined in eutopic and ectopic endometrial tissues from women with (n=25) or without (n=25) endometriosis. Resistin mRNA and protein levels were determined in endometrial tissue using quantitative real-time reverse transcription PCR and Western blotting, following adipokine profiling arrays. Resistin protein was detected in human endometrial tissues using an adipokine array test. Resistin mRNA and protein levels were significantly higher in ectopic endometrial tissue of patients with endometriosis than in normal eutopic endometrial tissue. Our results indicate that resistin is differentially expressed in endometrial tissues from women with endometriosis and imply a role for resistin in endometriosis-associated pelvic inflammation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Detection of endometrial lesions by degree of linear polarization maps

NASA Astrophysics Data System (ADS)

Kim, Jihoon; Fazleabas, Asgerally; Walsh, Joseph T.

2010-02-01

Endometriosis is one of the most common causes of chronic pelvic pain and infertility and is characterized by the presence of endometrial glands and stroma outside of the uterine cavity. A novel laparoscopic polarization imaging system was designed to detect endometriosis by imaging endometrial lesions. Linearly polarized light with varying incident polarization angles illuminated endometrial lesions. Degree of linear polarization image maps of endometrial lesions were constructed by using remitted polarized light. The image maps were compared with regular laparoscopy image. The degree of linear polarization map contributed to the detection of endometriosis by revealing structures inside the lesion. The utilization of rotating incident polarization angle (IPA) for the linearly polarized light provides extended understanding of endometrial lesions. The developed polarization system with varying IPA and the collected image maps could provide improved characterization of endometrial lesions via higher visibility of the structure of the lesions and thereby improve diagnosis of endometriosis.

Proteomics-based approach identified differentially expressed proteins with potential roles in endometrial carcinoma.

PubMed

Li, Zhengyu; Min, Wenjiao; Huang, Canhua; Bai, Shujun; Tang, Minghai; Zhao, Xia

2010-01-01

We used proteomic approaches to identify altered expressed proteins in endometrial carcinoma, with the aim of discovering potential biomarkers or therapeutic targets for endometrial carcinoma. The global proteins extracted from endometrial carcinoma and normal endometrial tissues were separated by 2-dimensional electrophoresis and analyzed with PDQuest (Bio-Rad, Hercules, Calif) software. The differentially expressed spots were identified by mass spectrometry and searched against NCBInr protein database. Those proteins with potential roles were confirmed by Western blotting and immunohistochemical assays. Ninety-nine proteins were identified by mass spectrometry, and a cluster diagram analysis indicated that these proteins were involved in metabolism, cell transformation, protein folding, translation and modification, proliferation and apoptosis, signal transduction, cytoskeleton, and so on. In confirmatory immunoblotting and immunohistochemical analyses, overexpressions of epidermal fatty acid-binding protein, calcyphosine, and cyclophilin A were also observed in endometrial carcinoma tissues, which were consistent with the proteomic results. Our results suggested that these identified proteins, including epidermal fatty acid-binding protein, calcyphosine, and cyclophilin A, might be of potential values in the studies of endometrial carcinogenesis or investigations of diagnostic biomarkers or treatment targets for endometrial carcinoma.

Targeted mutation analysis of endometrial clear cell carcinoma.

PubMed

Hoang, Lien N; McConechy, Melissa K; Meng, Bo; McIntyre, John B; Ewanowich, Carol; Gilks, Cyril Blake; Huntsman, David G; Köbel, Martin; Lee, Cheng-Han

2015-04-01

Endometrial clear cell carcinomas (CCC) constitute fewer than 5% of all carcinomas of the endometrium. Currently, little is known regarding the genetic basis of endometrial CCC. We performed genomic and immunohistochemical analyses on 14 rigorously reviewed pure endometrial CCC. The genomic analysis consisted of sequencing the coding regions of 26 genes implicated previously in endometrial carcinoma. Twelve of 14 tumours displayed a prototypical CCC immunophenotype [napsin A+, hepatocyte nuclear factor-1β (HNF1β(+) ) and oestrogen receptor(-) ] and all showed intact mismatch repair protein expression. We detected mutations in 11 of 14 tumours, and there was a predominance of mutations involving genes that are mutated more frequently in endometrial serous carcinomas than in endometrioid carcinomas. Two tumours displayed a prototypical serous carcinoma mutation profile (concurrent TP53 and PPP2R1A mutations, without PTEN, CTNNB1 or ARID1A mutation). No mutations in PTEN, CTNNB1 or POLE were identified. The overall mutation profile of this cohort of endometrial CCC appears to be more serous-like than endometrioid-like, with a minor subset in the TP53-mutated CCC showing serous carcinoma profile. These findings provide new insights into the molecular features of morphologically prototypical endometrial CCC, and underscore the need for further investigations into the oncogenesis of endometrial CCC. © 2014 John Wiley & Sons Ltd.

Analysis of Protein Kinase C Delta (PKCδ) Expression in Endometrial Tumors

PubMed Central

Reno, Elaine M.; Haughian, James M.; Dimitrova, Irina K.; Jackson, Twila A.; Shroyer, Kenneth R; Bradford., Andrew P.

2007-01-01

Endometrial cancer is the most common gynecological malignancy in the US, however, its underlying molecular mechanisms are poorly understood and few prognostic indicators have been identified. The Protein Kinase C (PKC) family have been shown to regulate pathways critical to malignant transformation, and in endometrial tumors, changes in PKC expression and activity have been linked to a more aggressive phenotype and poor prognosis. We have recently shown that PKCδ is a critical regulator of apoptosis and cell survival in endometrial cancer cells; however, PKCδ levels in endometrial tumors had not been determined. We used immunohistochemistry to examine PKCδ protein levels in normal endometrium and endometrioid carcinomas of increasing grade. Normal endometrium exhibited abundant nuclear and cytoplasmic staining of PKCδ, confined to glandular epithelium. In endometrial tumors, decreased PKCδ expression, both in intensity and fraction of epithelial cells stained, was observed with increasing tumor grade, with PKCδ being preferentially lost from the nucleus. Consistent with these observations, endometrial cancer cell lines derived from poorly differentiated tumors exhibited reduced PKCδ levels relative to well-differentiated lines. Treatment of endometrial cancer cells with etoposide resulted in a translocation of PKCδ from cytoplasm to nucleus concomitant with induction of apoptosis. Decreased PKCδ expression, particularly in the nucleus, may compromise the ability of cells to undergo apoptosis, perhaps conferring resistance to chemotherapy. Our results indicate that loss of PKCδ is an indicator of endometrial malignancy and increasing grade of cancer. Thus, PKCδ may function as a tumor suppressor in endometrial cancer. PMID:17959229

Alterations of choline phospholipid metabolism in endometrial cancer are caused by choline kinase alpha overexpression and a hyperactivated deacylation pathway.

PubMed

Trousil, Sebastian; Lee, Patrizia; Pinato, David J; Ellis, James K; Dina, Roberto; Aboagye, Eric O; Keun, Hector C; Sharma, Rohini

2014-12-01

Metabolic rearrangements subsequent to malignant transformation are not well characterized in endometrial cancer. Identification of altered metabolites could facilitate imaging-guided diagnosis, treatment surveillance, and help to identify new therapeutic options. Here, we used high-resolution magic angle spinning magnetic resonance mass spectroscopy on endometrial cancer surgical specimens and normal endometrial tissue to investigate the key modulators that might explain metabolic changes, incorporating additional investigations using qRT-PCR, Western blotting, tissue microarrays (TMA), and uptake assays of [(3)H]-labeled choline. Lipid metabolism was severely dysregulated in endometrial cancer with various amino acids, inositols, nucleobases, and glutathione also altered. Among the most important lipid-related alterations were increased phosphocholine levels (increased 70% in endometrial cancer). Mechanistic investigations revealed that changes were not due to altered choline transporter expression, but rather due to increased expression of choline kinase α (CHKA) and an activated deacylation pathway, as indicated by upregulated expression of the catabolic enzymes LYPLA1, LYPLA2, and GPCPD1. We confirmed the significance of CHKA overexpression on a TMA, including a large series of endometrial hyperplasia, atypical hyperplasia, and adenocarcinoma tissues, supporting a role for CHKA in malignant transformation. Finally, we documented several-fold increases in the uptake of [(3)H]choline in endometrial cancer cell lines compared with normal endometrial stromal cells. Our results validate deregulated choline biochemistry as an important source of noninvasive imaging biomarkers for endometrial cancer. ©2014 American Association for Cancer Research.

Association of BMI and height with the risk of endometrial cancer, overall and by histological subtype: a population-based prospective cohort study in Japan.

PubMed

Kawachi, Asuka; Shimazu, Taichi; Budhathoki, Sanjeev; Sawada, Norie; Yamaji, Taiki; Iwasaki, Motoki; Inoue, Manami; Tsugane, Shoichiro

2018-04-18

Evidence on the association between BMI, height, and endometrial cancer risk, including by subtypes, among Asian populations remains limited. We evaluated the impact of BMI and height on the risk of endometrial cancer, overall and by histological subtype. We prospectively investigated 53 651 Japanese women aged 40-69 years. With an average follow-up duration of 18.6 years, 180 newly diagnosed endometrial cancers were reported, including 119 type 1 and 21 type 2. The association between BMI, height, and endometrial cancer risk was assessed using a Cox proportional hazards regression model with adjustment for potential confounders. Overweight and obesity were associated positively with the risk of endometrial cancer. Compared with BMI of 23.0-24.9 kg/m, hazard ratios (HRs) (95% confidence intervals) were 1.93 (1.17-3.16) for BMI of 27.0-29.9 kg/m and 2.37 (1.20-4.66) for BMI of at least 30.0 kg/m. On analysis by histological subtype, with each increase in BMI of 5 U, the estimated HR of type 1 endometrial cancer increased (HR=1.54, 95% confidence interval: 1.21-1.98), but HR of type 2 endometrial cancer was unaffected. There was no statistically significant association between height and endometrial cancer risk. In conclusion, the risk of endometrial cancer was elevated in women with a BMI of at least 27.0 kg/m. By histological subtype, BMI was associated with type 1, but not type 2 endometrial cancer risk among a population with a relatively low BMI compared with western populations.

Nonsteroidal Anti-inflammatory Drugs and Endometrial Carcinoma Mortality and Recurrence

PubMed Central

Felix, Ashley S.; Cohn, David E.; McMeekin, D. Scott; Mutch, David G.; Creasman, William T.; Thaker, Premal H.; Walker, Joan L.; Moore, Richard G.; Lele, Shashikant B.; Guntupalli, Saketh R.; Downs, Levi S.; Nagel, Christa I.; Boggess, John F.; Pearl, Michael L.; Ioffe, Olga B.; Park, Kay J.; Ali, Shamshad; Brinton, Louise A.

2017-01-01

Abstract Background: Recent data suggest that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reductions in endometrial cancer risk, yet very few have examined whether their use is related to prognosis among endometrial cancer patients. Methods: Study subjects comprised 4374 participants of the NRG Oncology/Gynecology Oncology Group 210 Study with endometrial carcinoma who completed a presurgical questionnaire that assessed history of regular prediagnostic NSAID use and endometrial cancer risk factors. Recurrences, vital status, and causes of death were obtained from medical records and cancer registries. Fine-Gray semiproportional hazards regression estimated adjusted subhazard ratios (HRs) and 95% confidence intervals (CIs) for associations of NSAID use with endometrial carcinoma–specific mortality and recurrence. Models were stratified by endometrial carcinoma type (ie, type I [endometrioid] vs type II [serous, clear cell, or carcinosarcoma]) and histology. Results: Five hundred fifty endometrial carcinoma–specific deaths and 737 recurrences occurred during a median of five years of follow-up. NSAID use was associated with 66% (HR = 1.66, 95% CI = 1.21 to 2.30) increased endometrial carcinoma–specific mortality among women with type I cancers. Associations were statistically significant for former and current users, and strongest among former users who used NSAIDs for 10 years or longer (HR = 2.23, 95% CI = 1.19 to 4.18, two-sided Ptrend = .01). NSAID use was not associated with recurrence or endometrial carcinoma–specific mortality among women with type II tumors. Conclusions: In this study, use of NSAIDs was associated with increased endometrial carcinoma–specific mortality, especially in patients with type I tumors. Barring a clear biologic mechanism by which NSAIDs would increase the risk of cause-specific mortality, cautious interpretation is warranted. PMID:28376204

Gap junction blockade induces apoptosis in human endometrial stromal cells.

PubMed

Yu, Jie; Berga, Sarah L; Zou, Wei; Sun, He-Ying; Johnston-MacAnanny, Erika; Yalcinkaya, Tamer; Sidell, Neil; Bagchi, Indrani C; Bagchi, Milan K; Taylor, Robert N

2014-07-01

One of the most dynamic adult human tissues is the endometrium. Through coordinated, cyclical proliferation, differentiation, leukocyte recruitment, apoptosis, and desquamation, the uterine lining is expanded and shed monthly, unless pregnancy is established. Errors in these steps potentially cause endometrial dysfunction, abnormal uterine bleeding, failed embryonic implantation, infertility, or endometrial carcinoma. Our prior studies showed that gap junctions comprised of Gap junction alpha-1 (GJA1) protein, also known as connexin 43 (CX43), subunits are critical to endometrial stromal cell differentiation. The current studies were undertaken to explore the mechanism of endometrial dysfunction when gap junction intercellular communication (GJIC) is disrupted. Gap junction blockade by two distinct GJIC inhibitors, 18α-glycyrrhetinic acid (AGA) and octanol (OcOH), suppressed proliferation and induced apoptosis in endometrial stromal cells, as manifested by reduced biomarkers of cell viability, increased TUNEL staining, caspase-3 activation, sub-G1 chromosomal DNA complement, as well as shortened telomere length. Unexpectedly, we also observed that the chemical inhibitors blocked CX43 gene expression. Moreover, when endometrial stromal cells were induced to undergo hormonal decidualization, following a 7-day exposure to 10 nM 17β-estradiol + 100 nM progesterone + 0.5 mM dibutyryl cAMP, characteristic epithelioid changes in cell shape and secretion of prolactin were blunted in the presence of AGA or OcOH, recapitulating effects of RNA interference of CX43. Our findings indicate that endometrial stromal cell proliferation and maintenance of decidualized endometrial function are GJIC-dependent, and that disruption of gap junctions induces endometrial stromal cell apoptosis. These observations may have important implications for several common clinical endometrial pathologies. © 2014 Wiley Periodicals, Inc.

Prevalence of endometrial polyps coexisting with uterine fibroids and associated factors

PubMed Central

Kınay, Tuğba; Öztürk Başarır, Zehra; Fırtına Tuncer, Serap; Akpınar, Funda; Kayıkçıoğlu, Fulya; Koç, Sevgi

2016-01-01

Objective: The aim of the study was to investigate the prevalence of endometrial polyps in patients with uterine fibroids and associated factors of coexistence of these two pathologies. Materials and Methods: The medical records of 772 patients who underwent hysterectomy because of uterine fibroids were retrospectively reviewed. Patients were divided into two groups according to the presence of endometrial polyps in the histopathologic examination. Demographic, clinical and histopathologic findings of the patients with and without endometrial polyps were compared. Student’s t-test, Mann-Whitney U test, Pearson’s Chi-square test, and logistic regression analysis were used for statistical analysis. Results: The prevalence of the endometrial polyps in uterine fibroid cases was found 20.1% (n=155). Age ≥45 years (odds ratio [OR] 1.61; 95% confidence interval [CI]: [1.06-2.44]; p=0.014), presence of hypertension (23.9% vs. 17.5%; p=0.047), endometrial hyperplasia (OR 4.00; 95% CI: [1.92-8.33]; p<0.001) and cervical polyps (OR 3.13; 95% CI: [1.69-5.88]; p<0.001) were significantly associated with the coexistence of endometrial polyps and uterine fibroids. Endometrial polyps were more common in patients with ≥2 fibroids (p=0.023) and largest fibroid <8 cm (p=0.009). A negative correlation was found between condom use and endometrial polyps (8.1% vs. 3.9%; p=0.044). Conclusions: The prevalence of the endometrial polyps coexisting with uterine fibroids was 20.1%. Age, hypertension, endometrial hyperplasia, cervical polyps, and number of fibroids were positively correlated; condom use and size of largest fibroid were negatively correlated with the coexistence of these two pathologies. PMID:28913086

Increased expression of placental growth factor in high-grade endometrial carcinoma

PubMed Central

COENEGRACHTS, LIEVE; SCHRAUWEN, STEFANIE; VAN BREE, RITA; DESPIERRE, EVELYN; LUYTEN, CATHERINE; JONCKX, BART; STASSEN, JEAN MARIE; VERGOTE, IGNACE; AMANT, FRÉDÉRIC

2013-01-01

Placental growth factor (PlGF), a homolog of vascular endothelial growth factor (VEGF), exerts pleiotropic functions in cancer by affecting tumor cells as well as endothelial and inflammatory cells. Moreover, PlGF expression correlates with tumor stage, recurrence, metastasis and patient outcome in different types of cancer. Recently, administration of anti-PlGF therapy reduced tumor growth and metastasis in preclinical tumor models. In the present study, we evaluated the diagnostic and prognostic value of systemic and local expression of PlGF in primary endometrial carcinomas. PlGF levels in tumor lysates (n=128) and serum (n=88) of patients with primary endometrial cancer were determined using ELISA. PlGF mRNA expression in endometrial carcinoma tissues was quantified by quantitative qRT-PCR. Results were compared to endometrial cancer stage and grade. Systemic PlGF levels were not altered in patients with endometrial cancer (FIGO stage I-II-III) as compared to healthy controls. Only in FIGO stage IV patients, serum PlGF levels were slightly increased. Local PlGF mRNA and protein expression in endometrial tumors progressively increased with tumor grade. In endometrioid carcinomas, PlGF mRNA expression was significantly increased in endometrioid grade 3 tumors as compared to normal endometrial tissue. PlGF protein expression was significantly increased in endometrioid grade 2 and 3 carcinomas and in serous carcinomas as compared to normal endometrial tissue. Our study showed that systemic/serum PlGF levels cannot be used as a diagnostic or prognostic marker in endometrial cancer. However, the increased local expression of PlGF, primarily in high-grade carcinomas, underscores the possibility for preclinical assessment of anti-PlGF therapy in endometrial cancer. PMID:23232836

Increased expression of placental growth factor in high-grade endometrial carcinoma.

PubMed

Coenegrachts, Lieve; Schrauwen, Stefanie; Van Bree, Rita; Despierre, Evelyn; Luyten, Catherine; Jonckx, Bart; Stassen, Jean Marie; Vergote, Ignace; Amant, Frédéric

2013-02-01

Placental growth factor (PlGF), a homolog of vascular endothelial growth factor (VEGF), exerts pleiotropic functions in cancer by affecting tumor cells as well as endothelial and inflammatory cells. Moreover, PlGF expression correlates with tumor stage, recurrence, metastasis and patient outcome in different types of cancer. Recently, administration of anti-PlGF therapy reduced tumor growth and metastasis in preclinical tumor models. In the present study, we evaluated the diagnostic and prognostic value of systemic and local expression of PlGF in primary endometrial carcinomas. PlGF levels in tumor lysates (n=128) and serum (n=88) of patients with primary endometrial cancer were determined using ELISA. PlGF mRNA expression in endometrial carcinoma tissues was quantified by quantitative qRT-PCR. Results were compared to endometrial cancer stage and grade. Systemic PlGF levels were not altered in patients with endometrial cancer (FIGO stage I-II-III) as compared to healthy controls. Only in FIGO stage IV patients, serum PlGF levels were slightly increased. Local PlGF mRNA and protein expression in endometrial tumors progressively increased with tumor grade. In endometrioid carcinomas, PlGF mRNA expression was significantly increased in endometrioid grade 3 tumors as compared to normal endometrial tissue. PlGF protein expression was significantly increased in endometrioid grade 2 and 3 carcinomas and in serous carcinomas as compared to normal endometrial tissue. Our study showed that systemic/serum PlGF levels cannot be used as a diagnostic or prognostic marker in endometrial cancer. However, the increased local expression of PlGF, primarily in high-grade carcinomas, underscores the possibility for preclinical assessment of anti-PlGF therapy in endometrial cancer.

[Impaired endometrial receptivity in primary infertility in women with undifferentiated connective tissue dysplasia and hereditary thrombophilia].

PubMed

Zanozin, A S; Demura, T A; Kolosovsky, D Yu; Faizullina, N M; Kogan, E A

The concurrence of undifferentiated connective tissue dysplasia (uCTD) and hereditary thrombophilia (HT) often accompanies female infertility, in the pathogenesis of which impaired endometrial receptivity plays an important role. to investigate endometrial morphological and immunophenotypic features in patients with primary infertility in the presence of uCTD and HT. The pipelle endometrial biopsy specimens taken in the implantation window were examined in 81 patients, including 13 women with a clinical diagnosis of uCTD, 40 with HT, 19 with uCTD concurrent with HT, and in a control group of 9 heathy surrogate mothers. Morphological, immunohistochemical, and morphometric examinations were done to study the paraffin-embedded endometrial biopsy sections stained with hematoxylin and eosin, pikrofuksin by van Gieson, and with toluidine blue. Immunohistochemical tests were carried out using primary antibodies against ER, PgR, LIF, PAI-1, VEGF, Collagen I, Collagen III, fibronectin, laminin, MMP-2, and MMP-9. The uCTD, HT, and uCTD + HT groups were found to have signs of decreased endometrial receptivity as dramatically lower counts of mature pinopodes, slower endometrial maturation, reduced expression of the receptivity marker LIF, and deviations of the stromal progesterone-estrogen index from the normal value. Sclerotic foci with type III collagen accumulation were detected in the endometrial stroma. uCTD and HT and especially their concurrence are commonly a concomitant disease and risk factors for infertility in women due to impaired endometrial receptivity. In uCTD, connective tissue remodeling processes are substantially retarded, which ultimately leads to increased processes of endometrial stromal sclerosis, reduced endometrial receptivity, and infertility. The most pronounced morphological and immunophenotypical changes have been ascertained to develop in the uCTD + NT group. The findings may be used to predict and devise new infertility treatments in patients with uCTD + NT.

Aspirin use and endometrial cancer risk and survival.

PubMed

Takiuchi, Tsuyoshi; Blake, Erin A; Matsuo, Koji; Sood, Anil K; Brasky, Theodore M

2018-01-01

The role of acetylsalicylic acid (aspirin) as a chemo-preventive and adjuvant therapeutic agent for cancers is generating attention. Mounting evidence indicates that aspirin reduces the incidence and mortality of certain obesity-related cancers, particularly colorectal cancer. In endometrial cancer, previous studies examining the effect of aspirin remain inconsistent as to the reduction in the risk of endometrial cancer. While some evidence indicates protective effects in obese women, other studies have showed a potential deleterious effect of these medications on endometrial cancer outcomes. However, exposure measurement across studies has been inconsistent in recording dose, duration, and frequency of use; thus making comparisons difficult. In this article, we review the evidence for the association between endometrial cancer and obesity, the pharmacological differences between regular- and low-dose aspirin, as well as the potential anti-tumor mechanism of aspirin, supporting a possible therapeutic effect on endometrial cancer. A proposed mechanism behind decreased cancer mortality in endometrial cancer may be a result of inhibition of metastasis via platelet inactivation and possible prostaglandin E 2 suppression by aspirin. Additionally, aspirin use in particular may have a secondary benefit for obesity-related comorbidities including cardiovascular disease in women with endometrial cancer. Although aspirin-related bleeding needs to be considered as a possible adverse effect, the benefits of aspirin therapy may exceed the potential risk in women with endometrial cancer. The current evidence reviewed herein has resulted in conflicting findings regarding the potential effect on endometrial cancer outcomes, thus indicating that future studies in this area are needed to resolve the effects of aspirin on endometrial cancer survival, particularly to identify specific populations that might benefit from aspirin use. Copyright © 2017 Elsevier Inc. All rights reserved.

Body mass index trumps age in decision for endometrial biopsy: cohort study of symptomatic premenopausal women.

PubMed

Wise, Michelle R; Gill, Premjit; Lensen, Sarah; Thompson, John M D; Farquhar, Cynthia M

2016-11-01

Clinical guidelines recommend that women with abnormal uterine bleeding with risk factors have an endometrial biopsy to exclude hyperplasia or cancer. Given the majority of endometrial cancer occurs in postmenopausal women, it has not been widely recognized that obesity is a significant risk factor for endometrial hyperplasia and cancer in young, symptomatic, premenopausal women. We sought to evaluate the effect of body mass index on risk of endometrial hyperplasia or cancer in premenopausal women with abnormal uterine bleeding. This was a retrospective cohort study in a single large urban secondary women's health service. Participants were 916 premenopausal women referred for abnormal uterine bleeding of any cause and had an endometrial biopsy from 2008 through 2014. The primary outcome was complex endometrial hyperplasia (with or without atypia) or endometrial cancer. Almost 5% of participants had complex endometrial hyperplasia or cancer. After adjusting for clinical and demographic factors, women with a measured body mass index ≥30 kg/m 2 were 4 times more likely to develop complex hyperplasia or cancer (95% confidence interval, 1.36-11.74). Other risk factors were nulliparity (adjusted odds ratio, 3.08; 95% confidence interval, 1.43-6.64) and anemia (adjusted odds ratio, 2.23; 95% confidence interval, 1.14-4.35). Age, diabetes, and menstrual history were not significant. Obesity is an important risk factor for complex endometrial hyperplasia or cancer in premenopausal women with abnormal uterine bleeding who had an endometrial biopsy in a secondary gynecology service. As over half of women with the outcome in this study were age <45 years, deciding to biopsy primarily based on age, as currently recommended in national guidelines, potentially misses many cases or delays diagnosis. Body mass index should be the first stratification in the decision to perform endometrial biopsy and/or to refer secondary gynecology services. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular changes preceding endometrial and ovarian cancer: a study of consecutive endometrial specimens from Lynch syndrome surveillance.

PubMed

Niskakoski, Anni; Pasanen, Annukka; Lassus, Heini; Renkonen-Sinisalo, Laura; Kaur, Sippy; Mecklin, Jukka-Pekka; Bützow, Ralf; Peltomäki, Päivi

2018-03-27

Molecular alterations preceding endometrial and ovarian cancer and the sequence of events are unknown. Consecutive specimens from lifelong surveillance for Lynch syndrome provides a natural setting to address such questions. To molecularly define the multistep gynecological tumorigenesis, DNA mismatch repair gene mutation carriers with endometrial or ovarian carcinoma or endometrial hyperplasia were identified from a nation-wide registry and endometrial biopsy specimens taken from these individuals during 20 years of screening were collected. A total of 213 endometrial and ovarian specimens from Lynch syndrome individuals and 197 histology-matched (non-serous) samples from sporadic cases were available for this investigation. The specimens were profiled for markers linked to endometrial and ovarian tumorigenesis, including ARID1A protein expression, mismatch repair status, and tumor suppressor gene promoter methylation. In Lynch syndrome-associated endometrial and ovarian carcinomas, ARID1A protein was lost in 61-100% and mismatch repair was deficient in 97-100%, compared to 0-17% and 14-44% in sporadic cases (P = 0.000). ARID1A loss appeared in complex hyperplasia and deficient mismatch repair and tumor suppressor gene promoter methylation in histologically normal endometrium. Despite quantitative differences between Lynch syndrome and sporadic cases, ARID1A expression, mismatch repair, and tumor suppressor gene promoter methylation divided endometrial samples from both patient groups into three categories of increasing abnormality, comprising normal endometrium and simple hyperplasia (I), complex hyperplasia with or without atypia (II), and endometrial cancer (III). Complex hyperplasias without vs. with atypia were molecularly indistinguishable. In conclusion, surveillance specimens from Lynch syndrome identify mismatch repair deficiency, tumor suppressor gene promoter methylation, and ARID1A loss as early changes in tumor development. Our findings are clinically relevant for the classification of endometrial hyperplasias and have potential implications in cancer prevention in Lynch syndrome and beyond.

A comparative study of Cyclofem and depot medroxyprogesterone acetate (DMPA) effects on endometrial vasculature.

PubMed

Simbar, Masoumeh; Tehrani, Fahimeh Ramezani; Hashemi, Zeinab; Zham, Hananeh; Fraser, Ian S

2007-10-01

The most common reason for discontinuation of long-acting progestogen-only contraceptives is irregular bleeding following local endometrial vascular changes. To reduce unpredictable bleeding episodes among depot medroxyprogesterone acetate (DMPA) users, the combined injectable contraceptive, Cyclofem, was offered as an alternative. However, there is a gap in our knowledge about the effects of Cyclofem on the endometrial vasculature and patterns of bleeding. This study aimed to compare the effects of Cyclofem and DMPA on endometrial vascular density, endometrial histology and pattern of bleeding. Sixty-eight healthy women with regular menstrual bleeding and seeking injectable long-acting contraceptives were recruited. Two endometrial samples (before and 3 to 6 months after initial exposure to DMPA or Cyclofem) were collected from each participant. The samples were stained using an immunohistochemical method and anti-CD34 to visualise the endometrial vasculature. Endometrial vascular density was assessed using standard techniques. Sixty-eight women were randomly assigned to Cyclofem (38 women) or DMPA (30 women). Endometrial vascular density was 149.3 +/- 6.7 (mean +/- SD)/mm(2) before injection. This significantly decreased to 132.4 +/- 12.2 after DMPA use, and from 151.9 +/- 5.8 to 131.8 +/- 12.8 vessels/mm(2) following Cyclofem use (paired t-test, p <0.05). However, there was no significant difference between endometrial vascular density during treatment with Cyclofem or DMPA. Total bleeding days in the first and second 3-month time intervals were 28 +/- 23 and 18 +/- 12 days in DMPA users and 22 +/- 14 and 16 +/- 9 days in Cyclofem users, respectively, Spotting was the most common type of bleeding experienced, and atrophic endometrium was the most common histological pattern observed in both groups. This study demonstrated that both Cyclofem and DMPA use are associated with decreased endometrial vascular density and atrophic endometrium, in addition to irregular bleeding, mainly spotting. There was no significant difference in bleeding patterns or endometrial findings observed for these two injectable contraceptives in Iranian women.

Sterol regulatory element binding protein-1 (SREBP1) gene expression is similarly increased in polycystic ovary syndrome and endometrial cancer.

PubMed

Shafiee, Mohamad N; Mongan, Nigel; Seedhouse, Claire; Chapman, Caroline; Deen, Suha; Abu, Jafaru; Atiomo, William

2017-05-01

Women with polycystic ovary syndrome have a three-fold higher risk of endometrial cancer. Insulin resistance and hyperlipidemia may be pertinent factors in the pathogenesis of both conditions. The aim of this study was to investigate endometrial sterol regulatory element binding protein-1 gene expression in polycystic ovary syndrome and endometrial cancer endometrium, and to correlate endometrial sterol regulatory element binding protein-1 gene expression with serum lipid profiles. A cross-sectional study was performed at Nottingham University Hospital, UK. A total of 102 women (polycystic ovary syndrome, endometrial cancer and controls; 34 participants in each group) were recruited. Clinical and biochemical assessments were performed before endometrial biopsies were obtained from all participants. Taqman real-time polymerase chain reaction for endometrial sterol regulatory element binding protein-1 gene and its systemic protein expression were analyzed. The body mass indices of women with polycystic ovary syndrome (29.28 ± 2.91 kg/m 2 ) and controls (28.58 ± 2.62 kg/m 2 ) were not significantly different. Women with endometrial cancer had a higher mean body mass index (32.22 ± 5.70 kg/m 2 ). Sterol regulatory element binding protein-1 gene expression was significantly increased in polycystic ovary syndrome and endometrial cancer endometrium compared with controls (p < 0.0001). Sterol regulatory element binding protein-1 gene expression was positively correlated with body mass index (r = 0.017, p = 0.921) and waist-hip ratio (r = 0.023, p = 0.544) in polycystic ovary syndrome, but this was not statistically significant. Similarly, statistically insignificant positive correlations were found between endometrial sterol regulatory element binding protein-1 gene expression and body mass index in endometrial cancer (r = 0.643, p = 0.06) and waist-hip ratio (r = 0.096, p = 0.073). Sterol regulatory element binding protein-1 gene expression was significantly positively correlated with triglyceride in both polycystic ovary syndrome and endometrial cancer (p = 0.028 and p = 0.027, respectively). Quantitative serum sterol regulatory element binding protein-1 gene correlated with endometrial gene expression (p < 0.05). Sterol regulatory element binding protein-1 gene expression is significantly increased in the endometrium of women with polycystic ovary syndrome and women with endometrial cancer compared with controls and positively correlates with serum triglyceride in both polycystic ovary syndrome and endometrial cancer. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

Prospective endometrial assessment of breast cancer patients treated with third generation aromatase inhibitors.

PubMed

Garuti, Giancarlo; Cellani, Fulvia; Centinaio, Giovanna; Montanari, Giuseppe; Nalli, Giulio; Luerti, Massimo

2006-11-01

A prospective evaluation of the effects on endometrium of third generation aromatase inhibitors (AIs), administered as adjuvant up-front therapy or switched therapy in menopausal patients suffering from breast cancer. Forty-five patients suffering from estrogen-receptor positive breast cancer were treated with AIs as adjuvant endocrine therapy; 27 patients switched from tamoxifen to AIs (group 1) due to adverse medical events related to tamoxifen intake (22 patients) or to an extended endocrine treatment after 60 months of tamoxifen therapy (5 patients); whereas 18 patients received AIs as up-front adjuvant therapy (group 2). All patients underwent endometrial investigation before the start of AIs therapy and, thereafter, at 12 month intervals. Endometrial assessment was based on Transvaginal Ultrasonography (TU), followed by hysteroscopy and endometrial biopsy when a double layered endometrial stripe above 4 mm was measured on the longitudinal plane of uterine scanning. Six patients, showing endometrial hyperplasia before the start of AIs therapy, underwent hysteroscopy on a yearly basis, disregarding the endometrial thickness measured by TU. Histopathologic results on endometrial biopsies represented the reference test in order to estimate the prevalence of endometrial morbidity. Demographic and clinical variables evaluated (age, parity, age at menarche and menopause, Body Mass Index, previous chemotherapy and radiotherapy) did not differ in groups 1 and 2. The average period of endometrial surveillance after the start of AIs therapy was 24.8 +/-10.8 months for group 1 and 21.4 +/- 11.5 months for group 2. A progressive decrease of endometrial thickness, from 8.2 +/- 5.0 to 3.0 +/- 1.2 in group 1 and from 4.7 +/- 4.3 to 1.9 +/- 0.3 in group 2, was found before the start and after 36-48 months of AIs therapy. The second line endometrial investigations' rate dropped from 70.3% to 12.5% in group 1 and from 27.7% to 0.0% in group 2, at baseline and after 36-48 months of AIs therapy, respectively. We found baseline endometrial abnormalities in 25.9% and in 22.2% of patients in groups 1 and 2 (P = 0.4), respectively. During AIs administration, an endometrial pathology was found in 1 patient of group 1 and in 3 patients of group 2. In 3 patients, the abnormality consisted of simple hyperplasias and in all these patients an abnormal endometrium (1 complex atypical hyperplasia and 2 simple hyperplasias) was already detected at baseline assessment. Only in 1 patient (2.2%) of group 2 did we find an emerging pathology, consisting of adenosarcoma harbored within an endometrial polyp, detected after 12 months of therapy with letrozole. In 3 out of 5 patients showing simple hyperplasia and in 1 patient showing atypical hyperplasia before the start of AIs therapy, we observed a reversal to normal endometrium and to simple hyperplasia, respectively, after 12 months of therapy with anastrozole. AIs delivered as up-front therapy for breast cancer have no effects on unspecific endometrial thickening. When administered as switched therapy after tamoxifen withdrawal, AIs may reverse tamoxifen-associated endometrial thickening. As a consequence, we reduced unnecessary second-line endometrial investigations. A low rate of emerging endometrial pathology was found during AIs therapy.

Evidence that the endometrial microbiota has an effect on implantation success or failure.

PubMed

Moreno, Inmaculada; Codoñer, Francisco M; Vilella, Felipe; Valbuena, Diana; Martinez-Blanch, Juan F; Jimenez-Almazán, Jorge; Alonso, Roberto; Alamá, Pilar; Remohí, Jose; Pellicer, Antonio; Ramon, Daniel; Simon, Carlos

2016-12-01

Bacterial cells in the human body account for 1-3% of total body weight and are at least equal in number to human cells. Recent research has focused on understanding how the different bacterial communities in the body (eg, gut, respiratory, skin, and vaginal microbiomes) predispose to health and disease. The microbiota of the reproductive tract has been inferred from the vaginal bacterial communities, and the uterus has been classically considered a sterile cavity. However, while the vaginal microbiota has been investigated in depth, there is a paucity of consistent data regarding the existence of an endometrial microbiota and its possible impact in reproductive function. This study sought to test the existence of an endometrial microbiota that differs from that in the vagina, assess its hormonal regulation, and analyze the impact of the endometrial microbial community on reproductive outcome in infertile patients undergoing in vitro fertilization. To identify the existence of an endometrial microbiota, paired samples of endometrial fluid and vaginal aspirates were obtained simultaneously from 13 fertile women in prereceptive and receptive phases within the same menstrual cycle (total samples analyzed n = 52). To investigate the hormonal regulation of the endometrial microbiota during the acquisition of endometrial receptivity, endometrial fluid was collected at prereceptive and receptive phases within the same cycle from 22 fertile women (n = 44). Finally, the reproductive impact of an altered endometrial microbiota in endometrial fluid was assessed by implantation, ongoing pregnancy, and live birth rates in 35 infertile patients undergoing in vitro fertilization (total samples n = 41) with a receptive endometrium diagnosed using the endometrial receptivity array. Genomic DNA was obtained either from endometrial fluid or vaginal aspirate and sequenced by 454 pyrosequencing of the V3-V5 region of the 16S ribosomal RNA (rRNA) gene; the resulting sequences were taxonomically assigned using QIIME. Data analysis was performed using R packages. The χ 2 test, Student t test, and analysis of variance were used for statistical analyses. When bacterial communities from paired endometrial fluid and vaginal aspirate samples within the same subjects were interrogated, different bacterial communities were detected between the uterine cavity and the vagina of some subjects. Based on its composition, the microbiota in the endometrial fluid, comprising up to 191 operational taxonomic units, was defined as a Lactobacillus-dominated microbiota (>90% Lactobacillus spp.) or a non-Lactobacillus-dominated microbiota (<90% Lactobacillus spp. with >10% of other bacteria). Although the endometrial microbiota was not hormonally regulated during the acquisition of endometrial receptivity, the presence of a non-Lactobacillus-dominated microbiota in a receptive endometrium was associated with significant decreases in implantation [60.7% vs 23.1% (P = .02)], pregnancy [70.6% vs 33.3% (P = .03)], ongoing pregnancy [58.8% vs 13.3% (P = .02)], and live birth [58.8% vs 6.7% (P = .002)] rates. Our results demonstrate the existence of an endometrial microbiota that is highly stable during the acquisition of endometrial receptivity. However, pathological modification of its profile is associated with poor reproductive outcomes for in vitro fertilization patients. This finding adds a novel microbiological dimension to the reproductive process. Copyright © 2016 Elsevier Inc. All rights reserved.

Does dilation and curettage versus expectant management for spontaneous abortion in patients undergoing in vitro fertilization affect subsequent endometrial development?

PubMed

Moon, Kimberly S; Richter, Kevin S; Levy, Michael J; Widra, Eric A

2009-11-01

In in vitro fertilization patients, treatment of spontaneous abortion with dilation and curettage (D&C) versus expectant management has no long-term effect on subsequent endometrial development, as measured by change in endometrial thickness. A transient reduction in endometrial thickness was found within the first 6 months after D&C, which is a novel finding, but it is likely to have little or no effect on pregnancy rates given the small absolute effect on endometrial thickness.

Intensity-Modulated Radiation Therapy, Cisplatin, and Bevacizumab Followed by Carboplatin and Paclitaxel in Treating Patients Who Have Undergone Surgery for Endometrial Cancer

ClinicalTrials.gov

2018-02-15

Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer AJCC v7; Stage IB Uterine Corpus Cancer AJCC v7; Stage II Uterine Corpus Cancer AJCC v7; Stage IIIA Uterine Corpus Cancer AJCC v7; Stage IIIB Uterine Corpus Cancer AJCC v7; Stage IIIC Uterine Corpus Cancer AJCC v7; Stage IVA Uterine Corpus Cancer AJCC v7; Stage IVB Uterine Corpus Cancer AJCC v7

The Role of Engineering Principles in the Medical Utilization of Electromagnetic Energies from kHz to Visible Light - Examples

NASA Astrophysics Data System (ADS)

Rosen, Arye; Rosen, Harel D.

2009-12-01

The use of RF/microwaves in medicine has increased dramatically over the last ten years. RF and microwave therapies for the treatment of cancer in humans are well documented, and are presently used in many cancer centers. RF treatment for supra ventricular arrhythmias, and more recently for the treatment of ventricular tachycardia, are currently employed by major hospitals. RF/microwave are also used in human subjects for the treatment of benign prostatic hyperplasia (BPH). In the last few years, several otolaryngological centers have been utilizing RF to treat upper airway obstruction and to alleviate sleep apnea. Many centers also utilize RF for the treatment of gastro-esophageal disease (GERD), for pain management, and for endometrial ablation. Balloon microwave catheters for ablating solid tumors, then forming cavities in those tumors for the local delivery of therapeutic agents, are currently being investigated. New modalities are being studied, such as RF/microwave for the enhancement of drug absorption and microwave septic wound treatment, microwave imaging for the detection of breast cancer, epidemiological studies on the effects of rats’ exposure to microwave, as well as tissue regeneration using electromagnetic fields. In addition, technology is presently being developed that allows for permanent implantation of microwave wireless sensors in humans. A permanently implantable intra-cranial pressure monitor is one such application of the latter technology. Many more areas of research are currently being investigated, a partial list of which is summarized here.

Tazemetostat in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Endometrial Cancer

ClinicalTrials.gov

2018-03-02

Grade 1 Endometrial Endometrioid Adenocarcinoma; Grade 2 Endometrial Endometrioid Adenocarcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma

Diet and endometrial cancer: a focus on the role of fruit and vegetable intake, Mediterranean diet and dietary inflammatory index in the endometrial cancer risk.

PubMed

Ricceri, Fulvio; Giraudo, Maria Teresa; Fasanelli, Francesca; Milanese, Dario; Sciannameo, Veronica; Fiorini, Laura; Sacerdote, Carlotta

2017-11-13

Endometrial cancer is the fourth most common cancer in European women. The major risk factors for endometrial cancer are related to the exposure of endometrium to estrogens not opposed to progestogens, that can lead to a chronic endometrial inflammation. Diet may play a role in cancer risk by modulating chronic inflammation. In the framework of a case-control study, we recruited 297 women with newly diagnosed endometrial cancer and 307 controls from Northern Italy. Using logistic regression, we investigated the role of fruit and vegetable intake, adherence to the Mediterranean diet (MD), and the dietary inflammatory index (DII) in endometrial cancer risk. Women in the highest quintile of vegetable intake had a statistically significantly lower endometrial cancer risk (adjusted OR 5th quintile vs 1st quintile: 0.34, 95% CI 0.17-0.68). Women with high adherence to the MD had a risk of endometrial cancer that was about half that of women with low adherence to the MD (adjusted OR: 0.51, 95% CI 0.39-0.86). A protective effect was detected for all the lower quintiles of DII, with the highest protective effect seen for the lowest quintile (adjusted OR 5th quintile vs 1st quintile: 3.28, 95% CI 1.30-8.26). These results suggest that high vegetable intake, adherence to the MD, and a low DII are related to a lower endometrial cancer risk, with several putative connected biological mechanisms that strengthen the biological plausibility of this association.

Expression of HOXA10 in endometrial hyperplasia and adenocarcinoma and regulation by sex hormones in vitro.

PubMed

Zhong, Gang; Wang, Yan; Liu, Xuemei

2011-07-01

The objective of the study was to determine the expression of HOXA10 in human endometrial tissue in endometrial hyperplasia and carcinomas, and regulation by sex steroids in Ishikawa cells. Endometrial tissue was obtained from 133 subjects with normal endometria, endometrial hyperplasia, or endometrial adenocarcinoma. Among 133 specimens, 20 were normal endometria, 19 were simple hyperplasias without atypia, 20 were complex hyperplasias without atypia, 33 were atypical hyperplasias, and 41 were endometrial adenocarcinomas. The expression of HOXA10 was analyzed by immunohistochemistry. Ishikawa cell lines were incubated with 17β estradiol (10⁻⁸ mol/L) alone, medroxyprogesterone acetate (10⁻⁶ mol/L) alone, or the combination of estrogen and progesterone for 48 hours, respectively. In certain experiments, the antiprogestin antagonist, RU486 (10⁻⁵ mol/L), was also added to Ishikawa cells along with estradiol and medroxyprogesterone acetate for 48 hours. The expression of HOXA10 gene was detected by reverse transcriptase-polymerase chain reaction and Western blotting. HOXA10 was expressed in both normal and neoplastic endometria. No significant difference in HOXA10 expression was found between normal and hyperplastic endometrial tissues. The expression of HOXA10 was decreased in endometrial adenocarcinomas compared with normal endometria. Estrogen alone, progestin alone, or progestin combined with estrogen could significantly increase the expression of HOXA10 gene (P<0.05). RU486 could inhibit the effect of up-regulation of HOXA10 expression by progestin. The expression of HOXA10 was deregulated in endometrial carcinomas and up-regulated by sex hormones.

Sugar-sweetened beverage intake and the risk of type I and type II endometrial cancer among postmenopausal women.

PubMed

Inoue-Choi, Maki; Robien, Kim; Mariani, Andrea; Cerhan, James R; Anderson, Kristin E

2013-12-01

Sugar-sweetened beverage (SSB) intake has been associated with an increased risk of obesity and type II diabetes. However, its association with endometrial cancer is unclear. We evaluated dietary intake of SSB, fruit juice, sugar-free beverages, sweets/baked goods, starch, and sugars among 23,039 postmenopausal women in the Iowa Women's Health Study. Incident estrogen-dependent type I and estrogen-independent type II endometrial cancers were identified via linkage with the Surveillance Epidemiology and End Results Registry. Risks of type I and type II endometrial cancers were separately compared by energy-adjusted dietary intake in Cox proportional hazards regression models. From 1986 to 2010, 506 type I and 89 type II incident endometrial cancers were identified. An increased risk of type I endometrial cancer was observed with increasing SSB intake after adjustment for body mass index (BMI) and other cofounders (Ptrend = 0.0005). Compared with nondrinkers of SSB, the risk was 78% higher [95% confidence intervals (CI), 1.32-2.40] among women in the highest quintile of SSB intake. The observed association was not modified by BMI, physical activity, history of diabetes, or cigarette smoking. Higher risk of type I endometrial cancer was also observed with higher intake of sugars. None of the dietary items included in the analysis was associated with type II endometrial cancer risk. Higher intake of SSB and sugars was associated with an increased risk of type I, but not type II, endometrial cancer. SSB intake may be a risk factor for type I endometrial cancer regardless of other lifestyle factors. ©2013 AACR.

Thickened Endometrium in Postmenopausal Women With an Initial Biopsy of Limited, Benign, Surface Endometrium: Clinical Outcome and Subsequent Pathologic Diagnosis.

PubMed

Dermawan, Josephine K T; Hur, Christine; Uberti, Maria G; Flyckt, Rebecca; Falcone, Tommaso; Brainard, Jennifer; Abdul-Karim, Fadi W

2018-05-10

Endometrial biopsy or curetting is indicated for postmenopausal women with abnormal uterine bleeding and/or thickened endometrium. Often, endometrial biopsy or curetting yields limited benign surface endometrium, which may indicate insufficient sampling. This study addresses the clinical outcome and subsequent pathologic diagnoses in postmenopausal women who received this initial diagnosis. Among a total of 370 endometrial biopsy or curetting between 2012 and 2015, 192 (52%) were diagnosed as limited benign surface endometrial epithelium. The women ranged in age from 55 to 91 yr old. Their clinical presentations mainly included postmenopausal bleeding, pelvic pain, and enlarged uterus. Primarily because the initial report was interpreted as "benign," 108 (57%) had no subsequent follow-up. Interestingly, women with an increased endometrial thickness were more likely to receive repeat evaluation. Among the 84 women who underwent follow-up endometrial sampling, 6 (7%) had hyperplasia with atypia or malignancy, 21 (25%) had a repeat diagnosis of limited surface sample, 4 (5%) had insufficient materials, and 53 (63%) had other benign findings. Among the subset of women who did receive subsequent follow-up, endometrial atypia or malignancies are more likely found in those with increased body mass index. In conclusion, a slight majority of women with postmenopausal bleeding and/or thickened endometrium had an initial limited surface endometrial sample. Most had no subsequent endometrial sampling. Among those with subsequent follow-up, the majority had benign findings. The study highlights the inconsistencies in adequacy criteria for endometrial sampling and the lack of standardization of subsequent management.

A Prospective Investigation of Coffee Drinking and Endometrial Cancer Incidence

PubMed Central

Gunter, Marc J.; Schaub, Jennifer A.; Xue, Xiaonan; Freedman, Neal D.; Gaudet, Mia M.; Rohan, Thomas E.; Hollenbeck, Albert R.; Sinha, Rashmi

2011-01-01

Coffee drinking may be associated with reduced risk of endometrial cancer; however, prospective data are limited. Further, it is not clear whether any association between coffee and endometrial cancer differs according to coffee caffeine content. The association of coffee drinking with incidence of endometrial cancer was evaluated among 226,732 women, aged 50–71, enrolled in the NIH-AARP Diet and Health Study who completed a baseline epidemiologic questionnaire. Following a mean 9.3 years of follow-up, data were available for 1,486 incident endometrial cancer cases. Cox proportional hazards models were used to estimate associations of coffee with endometrial cancer incidence. Sub-group analyses were performed according to smoking status, hormone therapy use (HT) and body habitus. Coffee drinking was inversely related to incidence of endometrial cancer (Hazard Ratio [HR] comparing drinking of >3 cups/day versus no cups=0.64, 95%CI, 0.51–0.80; Ptrend= 0.0004). The association of coffee with endometrial cancer risk was apparent for consumption of both regular (HR per cup= 0.90, 95%CI, 0.86–0.95) and decaffeinated coffee (HR per cup=0.93, 95%CI, 0.87–0.99). The relation of coffee with endometrial cancer incidence varied significantly by HT use (Pinteraction=0.03) with an association only apparent among HT-never users (HR comparing drinking >3 cups/day versus no cups= 0.54, 95%CI, 0.41–0.72; Ptrend=0.0005). Endometrial cancer incidence appears to be reduced among women that habitually drink coffee, an association that does not differ according to caffeine content. PMID:22021096

[Expression of Id1 and Id3 in endometrial carcinoma and their roles in regulating biological behaviors of endometrial carcinoma cells in vitro].

PubMed

Sun, Lili; Li, Xuenong; Liu, Guobing

2013-06-01

To investigate the expression of inhibitor of DNA differentiation/DNA binding 1 (Id1) and Id3 in endometrial carcinoma and explore their roles in regulating the proliferation, invasion, migration and adhesion of endometrial carcinoma cells in vitro. Id1 and Id3 expression in 4 fresh endometrial cancer tissue specimens and matched adjacent tissues were detected using Western blotting. Two endometrial cancer cell lines, HEC-1-B and RL-952, were both divided into 4 groups, namely the untreated group, blank virus group, promoter group and Id1/Id3 double-knockdown group, and their expressions of MMP2, CXCR4 and P21 were detected by qRT-PCR and Western blotting. The proliferation, invasion, migration and adhesion of the cells were evaluated with MTT, Transwell, wound-healing, and adhesion assays. Endometrial carcinoma tissues showed significantly higher Id1 and Id3 expression than the adjacent tissues (P<0.05). In the two endometrial carcinoma cell lines, Id1/Id3 double-knockdown significantly decreased MMP2 and CXCR4 expression and increased P21 expression at both mRNA and protein levels (P<0.05), and resulted in suppressed cell proliferation, invasion, migration and adhesion. Id1 and Id3 expressions are up-regulated in endometrial carcinoma to promote the proliferation, invasion, migration and adhesion of the tumor cells by increasing MMP2 and CXCR4 expression and reducing P21 expression. Therapies targeting Id1/Id3 can be a novel strategy for treatment of endometrial carcinoma.

Pain evaluation during gynaecological surveillance in women with Lynch syndrome.

PubMed

Helder-Woolderink, Jorien; de Bock, Geertruida; Hollema, Harry; van Oven, Magda; Mourits, Marian

2017-04-01

To evaluate perceived pain during repetitive annual endometrial sampling at gynaecologic surveillance in asymptomatic women with Lynch syndrome (LS) over time and in addition to symptomatic women without LS, undergoing single endometrial sampling. In this prospective study, 52 women with LS or first degree relatives who underwent repetitive annual gynaecological surveillance including endometrial sampling of which 33 were evaluated twice or more and 50 symptomatic women without LS who had single endometrial sampling, were included. Pain intensity was registered with VAS scores. Differences in pain intensities between subsequent visits (in LS) and between the two groups were evaluated. The use of painkillers before endometrial sampling was registered. If women with LS decided for preventive surgery, the reason was recorded. The LS group reported a median VAS score of 5.0 (range 0-10) at the first surveillance (n = 52) and at the second visit (n = 24). Women who repeatedly underwent endometrial sampling more often used painkillers for this procedure. During the study period 7/52 (13 %) women with LS choose for preventive surgery, another 4/52 (8 %) refused further endometrial sampling. Painful endometrial sampling was mentioned as main reason to quit screening. The median VAS score of the 50 symptomatic women was 5.0 (range 1-9). Endometrial sampling, irrespective of indication, is a painful procedure, with a median VAS score of 5.0. During subsequent procedures in women with LS, the median pain score does not aggravate although one in five women chose an alternative for endometrial sampling.

The fate of autologous endometrial mesenchymal stromal cells after application in the healthy equine uterus.

PubMed

Rink, Elisabeth; Beyer, Teresa; French, Hilari; Watson, Elaine; Aurich, Christine; Donadeu, Xavier

2018-05-23

Because of their distinct differentiation, immunomodulatory and migratory capacities, endometrial mesenchymal stromal cells (MSCs) may provide an optimum source of therapeutic cells not only in relation to the uterus but also for regeneration of other tissues. This study reports the fate of endometrial MSCs following intrauterine application in mares. Stromal cell fractions were isolated from endometrial biopsies taken from seven reproductively healthy mares, expanded and fluorescence-labeled in culture. MSCs (15 x 106) or PBS were autologously infused into each uterine horn during early diestrus and subsequently tracked by fluorescence microscopy and flow cytometry of endometrial biopsies and blood samples taken periodically after infusion. The inflammatory response to cell infusion was monitored in endometrial cytology samples. MSCs were detected in endometrial sections at 6, 12 and 24 hours but not later (7 or 14 days) after cell infusion. Cells were in all cases located in the uterine lumen, never within endometrial tissue. No fluorescence signal was detected in blood samples at any time point after infusion. Cytology analyses showed an increase in %PMN between 1 and 3 hours after uterine infusion with either MSCs or PBS, and a further increase by 6 hours only in mares infused with PBS. In summary, endometrial MSCs were detected in the uterine lumen for up to 24 h after infusion but did not migrate into healthy endometrium. Moreover, MSCs effectively attenuated the inflammatory response to uterine infusion. We conclude that endometrial MSCs obtained from routine uterine biopsies could provide a safe and effective cell source for treatment of inflammatory conditions of the uterus and potentially other tissues.

F-prostanoid receptor regulation of fibroblast growth factor 2 signaling in endometrial adenocarcinoma cells.

PubMed

Sales, Kurt J; Boddy, Sheila C; Williams, Alistair R W; Anderson, Richard A; Jabbour, Henry N

2007-08-01

Prostaglandin (PG) F(2alpha) is a potent bioactive lipid in the female reproductive tract, and exerts its function after coupling with its heptahelical G-protein-coupled receptor [F-series-prostanoid (FP) receptor] to initiate cell signaling and target gene transcription. In the present study, we found elevated expression of fibroblast growth factor (FGF) 2, FGF receptor 1 (FGFR1), and FP receptor, colocalized within the neoplastic epithelial cells of endometrial adenocarcinomas. We investigated a role for PGF(2alpha)-FP receptor interaction in modulating FGF2 expression and signaling using an endometrial adenocarcinoma cell line stably expressing the FP receptor to the levels detected in endometrial adenocarcinomas (FPS cells) and endometrial adenocarcinoma tissue explants. PGF(2alpha)-FP receptor activation rapidly induced FGF2 mRNA expression, and elevated FGF2 protein expression and secretion into the culture medium in FPS cells and endometrial adenocarcinoma explants. The effect of PGF(2alpha) on the expression and secretion of FGF2 could be abolished by treatment of FPS cells and endometrial tissues with an FP receptor antagonist (AL8810) and inhibitor of ERK (PD98059). Furthermore, we have shown that FGF2 can promote the expression of FGF2 and cyclooxygenase-2, and enhance proliferation of endometrial adenocarcinoma cells via the FGFR1 and ERK pathways, thereby establishing a positive feedback loop to regulate neoplastic epithelial cell function in endometrial adenocarcinomas.

[Evaluation of postmenopausal uterine bleeding by endometrial biopsy in-office hysteroscopy vs endometrial biopsy with manual vacuum aspiration in the office. Preliminary report].

PubMed

Hernández, José Arias; Franco, María Eugenia Lozano; Mendizábal, David Pablo Bulnes; Broca, Yrma Bocanegra; Escoto, Adrián Fores

2009-11-01

To compare endometrial biopsy by hysteroscopy vs manual endouterine aspiration in office, in patients of Climateric Clinic from Hospital Regional de Alta Especialidad de la Mujer Tabasco, with postmenopausal uterine bleeding. There were included patients that come from October 30 2007 to December 20 2008 to Climateric Clinic, with abnormal uterine bleeding and without hormonal replacement therapy. There were taken biopsy by hysteroscopy and AMEU. The histopathology results were compared. A total of 25 women were evaluated. The average age was 53 years (+/- 5.6). The delivery average was 3 births (+/- 1). We found polyps in 9 (37%) patients, endometrial atrophy in 3 (13%), cystic hyperplasia in 2 (8%), proliferative endometrium in 4 (17%), submucous myomas in 5 (21%) and neoplasia in 1 (4%). The correlation between endometrial biopsy by hysteroscopy and AMEU was 100% for endometrial atrophy, cystic hyperplasia, proliferativo endometrium and neoplasia. There was not correlation between manual endouterine aspiration and endometrial biopsy by hysteroscopy for polyps and submucous myomas. We didn't have complications during the procedures. Hysteroscopic endometrial biopsy seems to have the same histopathology results than AMEU for endometrial atrophy, cystic hyperplasia, proliferative endometrium and neoplasia, not for miomas and polyps. Hysteroscopy can give us the possibility to see miomas and polyps and treat surgical pathology at the same moment almost in all cases.

Role of emmprin in endometrial cancer.

PubMed

Nakamura, Keiichiro; Kodama, Junichi; Hongo, Atsushi; Hiramatsu, Yuji

2012-05-28

Extracellular matrix metalloproteinase inducer (Emmprin/CD147) is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Enriched on the surface of many tumor cells, emmprin promotes tumor growth, invasion, metastasis and angiogenesis. We evaluated the clinical importance of emmprin and investigated its role in endometrial cancer. Emmprin expression was examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. In addition, the biological functions and inhibitory effects of an emmprin knockdown were investigated in HEC-50B and KLE endometrial cancer cell lines. The levels of emmprin expression were significantly increased in the endometrial cancer specimens compared with the normal endometrium and endometrial hyperplasia specimens (p < 0.05). The disease-free survival (DFS) and overall survival (OS) rates of patients with high emmprin expression were significantly higher than those of patients with low emmprin expression (DFS: p < 0.001; OS: p < 0.001). Emmprin knockdown by the siRNA led to cell proliferation, migration and invasion through TGF-β, EGF, NF-κB, VEGF, MMP-2, and MMP-9 expression, which in turn resulted in increased levels of E-cadherin and reduced levels of Vimentin and Snail in endometrial cancer. The present findings suggest that low emmprin expression might be a predictor of favorable prognosis in endometrial cancer patients, and that emmprin may represent a potential therapeutic target for endometrial cancer.

Role of emmprin in endometrial cancer

PubMed Central

2012-01-01

Background Extracellular matrix metalloproteinase inducer (Emmprin/CD147) is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Enriched on the surface of many tumor cells, emmprin promotes tumor growth, invasion, metastasis and angiogenesis. We evaluated the clinical importance of emmprin and investigated its role in endometrial cancer. Methods Emmprin expression was examined in uterine normal endometrium, endometrial hyperplasia and cancer specimens by immunohistochemistry. In addition, the biological functions and inhibitory effects of an emmprin knockdown were investigated in HEC-50B and KLE endometrial cancer cell lines. Results The levels of emmprin expression were significantly increased in the endometrial cancer specimens compared with the normal endometrium and endometrial hyperplasia specimens (p < 0.05). The disease-free survival (DFS) and overall survival (OS) rates of patients with high emmprin expression were significantly higher than those of patients with low emmprin expression (DFS: p < 0.001; OS: p < 0.001). Emmprin knockdown by the siRNA led to cell proliferation, migration and invasion through TGF-β, EGF, NF-κB, VEGF, MMP-2, and MMP-9 expression, which in turn resulted in increased levels of E-cadherin and reduced levels of Vimentin and Snail in endometrial cancer. Conclusions The present findings suggest that low emmprin expression might be a predictor of favorable prognosis in endometrial cancer patients, and that emmprin may represent a potential therapeutic target for endometrial cancer. PMID:22640183

Determination of Heavy Metal Concentrations in Normal and Pathological Human Endometrial Biopsies and In Vitro Regulation of Gene Expression by Metals in the Ishikawa and Hec-1b Endometrial Cell Line

PubMed Central

Tomkiewicz, Céline; Leblanc, Alix; Pierre, Stéphane; El Balkhi, Souleiman; Le Frère-Belda, Marie-Aude; Lecuru, Fabrice; Poupon, Joël; Barouki, Robert; Aggerbeck, Martine; Coumoul, Xavier

2015-01-01

It is well known that several metals, such as lead, mercury, cadmium, and vanadium, can mimic the effects of estrogens (metallo-estrogens). Nevertheless, there are only a few studies that have assessed the effects of toxic metals on the female genital tract and, in particular, endometrial tissue. In this context, we measured the concentrations of several trace elements in human endometrial tissue samples from individuals with hyperplasia or adenocarcinoma and in normal tissues. Hyperplasic endometrial tissue has a 4-fold higher concentration of mercury than normal tissue. Mercury can affect both the AhR and ROS signaling pathways. Thus, we investigated the possible toxic effects of mercury by in vitro studies. We found that mercury increases oxidative stress (increased HO1 and NQO1 mRNA levels) and alters the cytoskeleton in the human endometrial Ishikawa cell line and to a lesser extent, in the “less-differentiated” human endometrial Hec-1b cells. The results might help to explain a potential link between this metal and the occurrence of endometrial hyperplasia. PMID:26600472

Expression and regulation of estrogen-converting enzymes in ectopic human endometrial tissue.

PubMed

Fechner, Sabine; Husen, Bettina; Thole, Hubert; Schmidt, Markus; Gashaw, Isabella; Kimmig, Rainer; Winterhager, Elke; Grümmer, Ruth

2007-10-01

To investigate the regulation of estrogen-converting enzymes in human ectopic endometrial tissue. Animal study. Academic medical center. Sixty female nude mice with implanted human endometrial tissue. Twenty-two premenopausal women undergoing endometrial biopsy or hysterectomy. Human endometrial tissue was implanted into the peritoneal cavity of nude mice, and the effect of therapeutic drugs on transcription of steroid receptors and estrogen-converting enzymes was analyzed. Transcript levels of steroid hormone receptors, 17beta-hydroxysteroid dehydrogenase type 1 and 2, aromatase, and steroid sulfatase as well as proliferation rate were analyzed in the human ectopic endometrial tissue. Steroid receptors and estrogen-converting enzymes were expressed in the ectopic human endometrial fragments. Application of medroxyprogesterone acetate, dydrogesterone, danazol, and the aromatase inhibitor finrozole significantly inhibited aromatase transcription. In addition, danazol caused a significant decrease in transcription of steroid sulfatase, and finrozole, of 17beta-hydroxysteroid dehydrogenase type 1 in parallel to a decrease in proliferation rate in the ectopic human endometrial tissue. Pharmacological regulation of transcription of estrogen-converting enzymes in human endometrium cultured in nude mice may help to develop new therapeutic concepts based on local regulation of estrogen metabolism in endometriosis.

Endometrial 'scratching': what the data show.

PubMed

Santamaria, Xavier; Katzorke, Nora; Simón, Carlos

2016-08-01

Since its first description in 2003, the endometrial scratching procedure has been the topic of over 1000 studies. This procedure, used to improve endometrial receptivity for assisted reproduction, is accessible - any gynecologist can easily perform it - and has been adapted into clinical routine by some reproductive units. However, the available data are controversial, and no biological plausibility exists to support the use of this intervention. This study aims to critically review the existing data, focusing on the last 2 years, regarding the efficiency of endometrial scratching. A total of five randomized controlled studies, one meta-analysis, and a systematic review related to endometrial scratching/injury were published in 2014 and 2015. Considerable heterogeneity exists among these studies regarding the selected population, type of treatment, and even timing and devices used to perform the endometrial injury. Importantly, none of these studies reported improved reproductive outcomes in terms of live birth rates following endometrial scratching. Overall, data from properly designed and powered randomized controlled studies demonstrate no beneficial effect of this intervention that is based on unknown biological effects. Endometrial scratching produces pain, costs money, and the side-effects of systematic scratching in the production of Asherman syndrome remain to be seen. Think before scratching.

Sox9 overexpression in uterine epithelia induces endometrial gland hyperplasia

PubMed Central

Gonzalez, Gabriel; Mehra, Shyamin; Wang, Ying; Akiyama, Haruhiko

2016-01-01

SOX9 is a high mobility group transcription factor that is required in many biological processes, including cartilage differentiation, endoderm progenitor maintenance, hair differentiation, and testis determination. SOX9 has also been linked to colorectal, prostate, and lung cancer. We found that SOX9 is expressed in the epithelium of the adult mouse and human uterus, predominantly marking the uterine glands. To determine if SOX9 plays a role in the development of endometrial cancer we overexpressed Sox9 in the uterine epithelium using a progesterone receptor-Cre mouse model. Sox9 overexpression in the uterine epithelium led to the formation of simple and complex cystic glandular structures in the endometrium of aged-females. Histological analysis revealed that these structures appeared morphologically similar to structures present in patients with endometrial hyperplastic lesions and endometrial polyps that are thought to be precursors of endometrial cancer. The molecular mechanisms that cause the glandular epithelium to become hyperplastic, leading to endometrial cancer are still poorly understood. These findings indicate that chronic overexpression of Sox9 in the uterine epithelium can induce the development of endometrial hyperplastic lesions. Thus, SOX9 expression may be a factor in the formation of endometrial cancer. PMID:27262401

[The effect of vaginal sildenafil citrate on uterine blood flow and endometrium in the infertile women].

PubMed

Malinova, M; Abouyta, T; Krasteva, M

2013-01-01

Evaluation of endometrial receptivity remains a challenge in clinical practice. Ultrasound evaluation of endometrial thickness and texture and measurement of uterine artery blood flow has been used for endometrial assessment. To investigate the role of combination of sildenafil citrate and serophene on endometrial thickness, endometrial volume, endometrial FI and VFI on Angiohistogram, RI and PI to a. uterine on the day of hCG, in prediction of IUI outcome in infertile women. Forty two patients were selected randomly who had anovulatory infertility. In Sildenafil citrate plus Serophene group (Group I), patients got 25 mg sildenafil citrate (Silden) vaginally and Serophene 100-150 mg orally, and in Serophene group (Group II), 100-150 mg of Serophene was given orally. Mean endometrial thickness and endometrial volume was 11.8 +/- 2.6 v/s 10.2 +/- 2.8 and 5.2 +/- 1.4 v/s 3.6 +/- 1.8 respectively in group I and in group II (p < 0.05). There was significant decrease in PI and RI to a. uterina in group I. Combination of Sildenafil citrate and Serophene is an effective agent as a first-line of treatment for ovulation induction.

p53 suppresses type II endometrial carcinomas in mice and governs endometrial tumour aggressiveness in humans

PubMed Central

Wild, Peter J; Ikenberg, Kristian; Fuchs, Thomas J; Rechsteiner, Markus; Georgiev, Strahil; Fankhauser, Niklaus; Noske, Aurelia; Roessle, Matthias; Caduff, Rosmarie; Dellas, Athanassios; Fink, Daniel; Moch, Holger; Krek, Wilhelm; Frew, Ian J

2012-01-01

Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium-specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours. PMID:22678923

Endometrial stromal tumors: the new WHO classification.

PubMed

Conklin, Christopher M J; Longacre, Teri A

2014-11-01

Endometrial stromal tumors are rare uterine mesenchymal neoplasms that have intrigued pathologists for years, not only because they commonly pose diagnostic dilemmas, but also because the classification and pathogenesis of these tumors has been widely debated. The current World Health Organization recognizes 4 categories of endometrial stromal tumor: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS). uterine sarcoma. These categories are defined by the presence of distinct translocations as well as tumor morphology and prognosis. Specifically, the JAZF1-SUZ12 (formerly JAZF1-JJAZ1) fusion identifies a large proportion of ESN and LG-ESSs, whereas the YWHAE-FAM22 translocation identifies HG-ESSs. The latter tumors appear to have a prognosis intermediate between LG-ESS and UUS, which exhibits no specific translocation pattern. This review (1) presents the clinicopathologic features of endometrial stromal tumors; (2) discusses their immunophenotype; and (3) highlights the recent advances in molecular genetics which explain their pathogenesis and lend support for a new classification system.

High prevalence of atypical hyperplasia in the endometrium of patients with epithelial ovarian cancer.

PubMed

Mingels, Marjanka J J M; Masadah, Rina; Geels, Yvette P; Otte-Höller, Irene; de Kievit, Ineke M; van der Laak, Jeroen A W M; van Ham, Maaike A P C; Bulten, Johan; Massuger, Leon F A G

2014-08-01

The aim of the present study is to determine the prevalence of endometrial premalignancies in women diagnosed with epithelial ovarian cancer (EOC). Endometrial and ovarian specimens of 186 patients with EOC were retrospectively selected using the nationwide pathology network and registry, and sections were comprehensively reviewed: 136 (73%) serous, 19 (10%) endometrioid, 15 (8%) mucinous, seven (4%) clear cell, and nine (5%) undifferentiated. Immunohistochemical phenotypes were compared for patients with serous EOC with concurrent endometrial pathology. In 31%, endometrial (pre)malignancy was found: carcinoma in 3%, endometrial intraepithelial carcinoma (EIC) in 4%, and atypical hyperplasia in 24%. Atypical hyperplasia was found in 47% of endometrioid EOCs but in 7% to 33% of other subtypes. Body mass index was higher concurrent to atypical hyperplasia (P=.001). Serous EOC and EIC immunophenotypes were comparable, whereas atypical hyperplasia was expressed differently. Apart from synchronous endometrial carcinoma, endometrial premalignancies should be taken into account when determining optimal treatment for women diagnosed with EOC. Copyright© by the American Society for Clinical Pathology.

Altered peroxisome-proliferator activated receptors expression in human endometrial cancer.

PubMed

Knapp, Paweł; Chabowski, Adrian; Błachnio-Zabielska, Agnieszka; Jarząbek, Katarzyna; Wołczyński, Sławomir

2012-01-01

Peroxisome proliferator-activated receptors (PPARs) belong to a family of nuclear hormone receptors acting as transcriptional factors, recently involved also in carcinogenesis. Present study was undertaken to evaluate the presence and subcellular localization of different PPAR isoforms (α, β, γ) in healthy endometrial tissue (n = 10) and endometrial carcinoma (FIGO I, endometrioides type, G1, n = 35). We sought to analyze PPARs mRNA content as well as protein immunohistochemical expression that was further quantified by Western Blot technique. For both PPARα and PPARβ, protein expression was significantly higher in endometrial cancers compared to normal endometrial mucosa. In opposite, PPARγ protein expression was lower in endometrial cancer cells. In each case, immunohistochemical reaction was confined to the perinuclear and/or nuclear region. At the transcriptional level, the content of mRNA of all PPAR subunits did not follow the protein pattern of changes. These results provide evidence for altered PPAR's protein expression and disregulation of posttranslational processes in endometrial cancers.

Endometrial cancer.

PubMed

Porter, Stephanie

2002-08-01

To provide an update for nurses involved in the care of women at risk or being treated for endometrial cancer. Review articles, research reports, and medical and nursing text-books. Endometrial cancer is the most common gynecologic malignancy. Although most women with endometrial cancer present with early stage disease and have an excellent chance of cure, approximately 6,600 women in the United States are expected to die from the disease in 2002. Treatment of patients with advanced or recurrent disease remains challenging, with no proven best standard of treatment. Nursing plays an important role in prevention and early detection of endometrial cancer, patient education, patient care, and rehabilitation.

FGFR2 alterations in endometrial carcinoma.

PubMed

Gatius, Sonia; Velasco, Ana; Azueta, Ainara; Santacana, Maria; Pallares, Judit; Valls, Joan; Dolcet, Xavier; Prat, Jaime; Matias-Guiu, Xavier

2011-11-01

Fibroblast growth factor receptor 2 (FGFR2) is a tyrosine kinase receptor involved in many biological processes such as embryogenesis, adult tissue homeostasis and cell proliferation. Mutations in FGFR2 have been reported in up to 10-12% of endometrial carcinomas identical to those found in congenital craniofacial disorders. Inhibition of FGFR2 could be a new therapeutic target in endometrial carcinoma. FGFR2 immunostaining was assessed in three tissue microarrays: one constructed from paraffin-embedded blocks of 60 samples of normal endometrium in different phases of menstrual cycle, and two tissue microarrays containing endometrial carcinoma samples (95 and 62 cases). FGFR2 expression was correlated with stage, histological type and grade as well as with immunostaining of PTEN, RASSF1A, estrogen and progesterone receptors, KI67, Cyclin D1, STAT-3 and SPRY2. FGFR2 mutations were assessed by PCR and direct sequencing, with DNA obtained from 31 paraffin-embedded endometrial carcinoma samples. In normal endometrium, FGFR2 expression was higher in the secretory than in the proliferative phase (P=0.001), with an inverse correlation with Ki67 (P=0.00032), suggesting a tumor-suppressor role for FGFR2 in normal endometrium. Cytoplasmic expression of FGFR2 was higher in endometrial carcinoma when compared with the atrophic endometrium from the same patients (P=0.0283), but was lower in comparison with normal endometrium from women in the menstrual cycle. Interestingly, nuclear staining was observed in some cases, and it was less frequent in endometrial carcinoma when compared with the adjacent atrophic endometrium (P=0.0465). There were no statistical differences when comparing superficial and myoinvasive endometrial carcinoma samples. Endometrioid endometrial carcinomas showed higher expression of FGFR2 than nonendometrioid endometrial carcinomas (fold change 2.56; P=0.0015). Grade III endometrioid endometrial carcinomas showed decreased FGFR2 expression when compared with grade II endometrioid endometrial carcinomas (P=0.0055). No differences were found regarding pathological stage. Two missense mutations of FGFR2 gene were detected in exons 6 and 11 (S252W and N549K, respectively; 6.45%). Results support the hypothesis that FGFR2 has a dual role in the endometrium, by inhibiting cell proliferation in normal endometrium during the menstrual cycle, but acting as an oncogene in endometrial carcinoma.

Surveying ourselves: examining the use of a web-based approach for a physician survey.

PubMed

Matteson, Kristen A; Anderson, Britta L; Pinto, Stephanie B; Lopes, Vrishali; Schulkin, Jay; Clark, Melissa A

2011-12-01

A survey was distributed, using a sequential mixed-mode approach, to a national sample of obstetrician-gynecologists. Differences between responses to the web-based mode and the on-paper mode were compared to determine if there were systematic differences between respondents. Only two differences in respondents between the two modes were identified. University-based physicians were more likely to complete the web-based mode than private practice physicians. Mail respondents reported a greater volume of endometrial ablations compared to online respondents. The web-based mode had better data quality than the paper-based mailed mode in terms of less missing and inappropriate responses. Together, these findings suggest that, although a few differences were identified, the web-based survey mode attained adequate representativeness and improved data quality. Given the metrics examined for this study, exclusive use of web-based data collection may be appropriate for physician surveys with a minimal reduction in sample coverage and without a reduction in data quality.

Endometrial Cancer Prevention (PDQ®)—Health Professional Version

Cancer.gov

Endometrial cancer prevention strategies are associated with endogenous and exogenous estrogen effects. Get detailed information about known risk factors and prevention strategies for endometrial cancer in this summary for clinicians.

Overexpression of microRNA-194 suppresses the epithelial-mesenchymal transition in targeting stem cell transcription factor Sox3 in endometrial carcinoma stem cells.

PubMed

Gong, Baolan; Yue, Yan; Wang, Renxiao; Zhang, Yi; Jin, Quanfang; Zhou, Xi

2017-06-01

The epithelial-mesenchymal transition is the key process driving cancer metastasis. MicroRNA-194 inhibits epithelial-mesenchymal transition in several cancers and its downregulation indicates a poor prognosis in human endometrial carcinoma. Self-renewal factor Sox3 induces epithelial-mesenchymal transition at gastrulation and is also involved epithelial-mesenchymal transition in several cancers. We intended to determine the roles of Sox3 in inducing epithelial-mesenchymal transition in endometrial cancer stem cells and the possible role of microRNA-194 in controlling Sox3 expression. Firstly, we found that Sox3 and microRNA-194 expressions were associated with the status of endometrial cancer stem cells in a panel of endometrial carcinoma tissue, the CD133+ cell was higher in tumorsphere than in differentiated cells, and overexpression of microRNA-194 would decrease CD133+ cell expression. Silencing of Sox3 in endometrial cancer stem cell upregulated the epithelial marker E-cadherin, downregulated the mesenchymal marker vimentin, and significantly reduced cell invasion in vitro; overexpression of Sox3 reversed these phenotypes. Furthermore, we discovered that the expression of Sox3 was suppressed by microRNA-194 through direct binding to the Sox3 3'-untranslated region. Ectopic expression of microRNA-194 in endometrial cancer stem cells induced a mesenchymal-epithelial transition by restoring E-cadherin expression, decreasing vimentin expression, and inhibiting cell invasion in vitro. Moreover, overexpression of microRNA-194 inhibited endometrial cancer stem cell invasion or metastasis in vivo by injection of adenovirus microRNA-194. These findings demonstrate the novel mechanism by which Sox3 contributes to endometrial cancer stem cell invasion and suggest that repression of Sox3 by microRNA-194 may have therapeutic potential to suppress endometrial carcinoma metastasis. The cancer stem cell marker, CD133, might be the surface marker of endometrial cancer stem cell.

The Regulation of Vascular Endothelial Growth Factor by Hypoxia and Prostaglandin F2α during Human Endometrial Repair

PubMed Central

Maybin, Jacqueline A.; Hirani, Nikhil; Brown, Pamela; Jabbour, Henry N.

2011-01-01

Context: The human endometrium has an exceptional capacity for repeated repair after menses, but its regulation remains undefined. Premenstrually, progesterone levels fall and prostaglandin (PG) F2α synthesis increases, causing spiral arteriole constriction. We hypothesized that progesterone withdrawal, PGF2α, and hypoxia increase vascular endothelial growth factor (VEGF), an endometrial repair factor. Design and Results: Endometrial biopsies were collected (n = 47) with ethical approval and consent. VEGF mRNA, quantified by quantitative RT-PCR, was increased during menstruation (P < 0.01).VEGF protein was maximally secreted from proliferative endometrial explants. Treatment of an endometrial epithelial cell line and primary human endometrial stromal cells with 100 nm PGF2α or hypoxia (0.5% O2) resulted in significant increases in VEGF mRNA and protein. VEGF was maximal when cells were cotreated with PGF2α and hypoxia simultaneously (P < 0.05–0.001). Secretory-phase endometrial explants also showed an increase in VEGF with cotreatment (P < 0.05). However, proliferative-phase explants showed no increase in VEGF on treatment with PGF2α and/or hypoxia. Proliferative tissue was induced to increase VEGF mRNA expression when exposed to progesterone and its withdrawal in vitro but only in the presence of hypoxia and PG. Hypoxia-inducible factor-1α (HIF-1α) silencing with RNA interference suppressed hypoxia-induced VEGF expression in endometrial cells but did not alter PGF2α-induced VEGF expression. Conclusions: Endometrial VEGF is increased at the time of endometrial repair. Progesterone withdrawal, PGF2α, and hypoxia are necessary for this perimenstrual VEGF expression. Hypoxia acts via HIF-1α to increase VEGF, whereas PGF2α acts in a HIF-1α-independent manner. Hence, two pathways regulate the expression of VEGF during endometrial repair. PMID:21677035

ACR appropriateness criteria(®) on abnormal vaginal bleeding.

PubMed

Bennett, Genevieve L; Andreotti, Rochelle F; Lee, Susanna I; Dejesus Allison, Sandra O; Brown, Douglas L; Dubinsky, Theodore; Glanc, Phyllis; Mitchell, Donald G; Podrasky, Ann E; Shipp, Thomas D; Siegel, Cary Lynn; Wong-You-Cheong, Jade J; Zelop, Carolyn M

2011-07-01

In evaluating a woman with abnormal vaginal bleeding, imaging cannot replace definitive histologic diagnosis but often plays an important role in screening, characterization of structural abnormalities, and directing appropriate patient care. Transvaginal ultrasound (TVUS) is generally the initial imaging modality of choice, with endometrial thickness a well-established predictor of endometrial disease in postmenopausal women. Endometrial thickness measurements of ≤5 mm and ≤4 mm have been advocated as appropriate upper threshold values to reasonably exclude endometrial carcinoma in postmenopausal women with vaginal bleeding; however, the best upper threshold endometrial thickness in the asymptomatic postmenopausal patient remains a subject of debate. Endometrial thickness in a premenopausal patient is a less reliable indicator of endometrial pathology since this may vary widely depending on the phase of menstrual cycle, and an upper threshold value for normal has not been well-established. Transabdominal ultrasound is generally an adjunct to TVUS and is most helpful when TVUS is not feasible or there is poor visualization of the endometrium. Hysterosonography may also allow for better delineation of both the endometrium and focal abnormalities in the endometrial cavity, leading to hysteroscopically directed biopsy or resection. Color and pulsed Doppler may provide additional characterization of a focal endometrial abnormality by demonstrating vascularity. MRI may also serve as an important problem-solving tool if the endometrium cannot be visualized on TVUS and hysterosonography is not possible, as well as for pretreatment planning of patients with suspected endometrial carcinoma. CT is generally not warranted for the evaluation of patients with abnormal bleeding, and an abnormal endometrium incidentally detected on CT should be further evaluated with TVUS. Copyright © 2011 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Long-term, adverse genitourinary outcomes among endometrial cancer survivors in a large, population-based cohort study.

PubMed

Soisson, Sean; Ganz, Patricia A; Gaffney, David; Rowe, Kerry; Snyder, John; Wan, Yuan; Deshmukh, Vikrant; Newman, Mike; Fraser, Alison; Smith, Ken; Herget, Kimberly; Hanson, Heidi A; Wu, Yelena P; Stanford, Joseph; Werner, Theresa L; Setiawan, Veronica Wendy; Hashibe, Mia

2018-03-01

With the increasing incidence of endometrial cancer, the high survival rate, and the large number of endometrial cancer survivors, investigations of long-term genitourinary outcomes are important for the management of these outcomes among endometrial cancer survivors. Cohorts of 2648 endometrial cancer survivors diagnosed in the state of Utah between 1997 and 2012 and 10,503 general population women were identified. All ICD-9 diagnosis codes were collected from the state's two largest healthcare systems and statewide databases. Multivariate Cox regression models were used to estimate hazard ratios at 1-5years and >5-10years after endometrial cancer diagnosis for genitourinary outcomes. Endometrial cancer survivors were at elevated risk for urinary system disorders between 1 and 5years (HR: 1.64, 95% CI: 1.50-1.78) and >5-10years (HR: 1.40, 95% CI: 1.26-1.56) and genital organ disorders between 1 and 5years (HR: 1.71, 95% CI: 1.58-2.03) and >5-10years (HR: 1.33, 95% CI: 1.19-1.49). Significantly elevated risk was observed among endometrial cancer survivors for renal failure, chronic kidney disease, urinary tract infections, and nonmalignant breast conditions, persisting between >5-10years. Between 1 and 5years after cancer diagnosis, those with higher stage, higher grade, older age and treated with radiation or chemotherapy were at higher risk for urinary disorders. Endometrial cancer survivors were at higher risk for many genitourinary outcomes compared to women from the general population. This study presents evidence suggesting the necessity of increased monitoring and counseling for genitourinary disorders for endometrial cancer patients both immediately after treatment cessation and for years afterwards. Copyright © 2018 Elsevier Inc. All rights reserved.

Role of dilatation and curettage performed for spontaneous or induced abortion in the etiology of endometrial thinning.

PubMed

Azumaguchi, Atsushi; Henmi, Hirofumi; Ohnishi, Hirofumi; Endo, Toshiaki; Saito, Tsuyoshi

2017-03-01

The aim of this study was to clarify the role of dilatation and curettage (D&C) performed for spontaneous or induced abortion in the etiology of endometrial thinning. This was a retrospective and cross-sectional study of 310 infertile patients from January 2013 through December 2015. Endometrial thickness observed 5-7 days after ovulation in a natural menstrual cycle was correlated with the number of D&C noted in each patient's history. Study 1 was an investigation of patients without D&C (group A: n = 232) and patients with D&C performed for spontaneous abortion (group B: n = 46). Study 2 was an investigation of patients in group A and patients with D&C performed for induced abortion (group C: n = 32). A significant negative correlation (P < 0.01) between endometrial thickness and number of D&C was observed in both studies. The mean endometrial thickness of the patients in group A was 10.9 ± 2.1 mm. The mean endometrial thickness of the patients in group B with one and ≥two D&C was 7.9 ± 2.3 and 6.9 ± 2.9 mm, respectively. The mean endometrial thickness of the patients in group C with one and ≥two D&C was 9.1 ± 2.3 and 7.8 ± 2.0 mm, respectively. There was a tendency toward gradual endometrial thinning following repeated procedures and the number of previous D&C was significantly associated with endometrial thinning (P < 0.001) in both studies. D&C performed for spontaneous or induced abortion may play a causal role in endometrial thinning. © 2017 Japan Society of Obstetrics and Gynecology.

Targeting histone deacetylases in endometrial cancer: a paradigm-shifting therapeutic strategy?

PubMed

Garmpis, N; Damaskos, C; Garmpi, A; Spartalis, E; Kalampokas, E; Kalampokas, T; Margonis, G-A; Schizas, D; Andreatos, N; Angelou, A; Lavaris, A; Athanasiou, A; Apostolou, K G; Spartalis, M; Damaskou, Z; Daskalopoulou, A; Diamantis, E; Tsivelekas, K; Alavanos, A; Valsami, S; Moschos, M M; Sampani, A; Nonni, A; Antoniou, E A; Mantas, D; Tsourouflis, G; Markatos, K; Kontzoglou, K; Perrea, D; Nikiteas, N; Kostakis, A; Dimitroulis, D

2018-02-01

Endometrial cancer is increasingly prevalent in western societies and affects mainly postmenopausal women; notably incidence rates have been rising by 1.9% per year on average since 2005. Although the early-stage endometrial cancer can be effectively managed with surgery, more advanced stages of the disease require multimodality treatment with varying results. In recent years, endometrial cancer has been extensively studied at the molecular level in an attempt to develop effective therapies. Recently, a family of compounds that alter epigenetic expression, namely histone deacetylase inhibitors, have shown promise as possible therapeutic agents in endometrial cancer. The present review aims to discuss the therapeutic potential of these agents. This literature review was performed using the MEDLINE database; the search terms histone, deacetylase, inhibitors, endometrial, targeted therapies for endometrial cancer were employed to identify relevant studies. We only reviewed English language publications and also considered studies that were not entirely focused on endometrial cancer. Ultimately, sixty-four articles published until January 2018 were incorporated into our review. Studies in cell cultures have demonstrated that histone deacetylase inhibitors exert their antineoplastic activity by promoting expression of p21WAF1 and p27KIP1, cyclin-dependent kinase inhibitors, that have important roles in cell cycle regulation; importantly, the transcription of specific genes (e.g., E-cadherin, PTEN) that are commonly silenced in endometrial cancer is also enhanced. In addition to these abstracts effects, novel compounds with histone deacetylase inhibitor activity (e.g., scriptaid, trichostatin, entinostat) have also demonstrated significant antineoplastic activity both in vitro and in vivo, by liming tumor growth, inducing apoptosis, inhibiting angiogenesis and potentiating the effects of chemotherapy. The applications of histone deacetylase inhibitors in endometrial cancer appear promising; nonetheless, additional trials are necessary to establish the therapeutic role, clinical utility, and safety of these promising compounds.

Decreased endometrial vascularity and receptivity in unexplained recurrent miscarriage patients during midluteal and early pregnancy phases.

PubMed

Tan, Shu-Yin; Hang, Fu; Purvarshi, Gowreesunkur; Li, Min-Qing; Meng, Da-Hua; Huang, Ling-Ling

2015-10-01

To evaluate the predictive value of three-dimensional (3D)-power Doppler sonography on recurrent miscarriage. The study patients were divided into a recurrent miscarriage group (30 cases) and a normal pregnancy group (21 cases). Measurement of endometrial thickness was performed using two-dimensional transvaginal ultrasound in the midluteal phase. The endometrial volume, vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) in midluteal and placenta volume, as well as the VI, FI, and VFI of early pregnancy were measured using Virtual Organ Computer-aided Analysis of 3D-power Doppler ultrasound. Endometrial thickness, endometrial volume, endometrial vascular data, VI, FI, and VFI of the midluteal phase were lower in the recurrent miscarriage group compared with the normal pregnancy group (p < 0.05). Placental volume, VI, and VFI during early pregnancy were lower in the miscarriage group compared with the normal pregnancy group (p < 0.05). There was no significant change in FI between the recurrent miscarriage and control groups during early pregnancy (p > 0.05). The predictive accuracy of endometrial thickness, endometrial volume, VI, FI, and VFI in the midluteal phase, and placenta volume, VI, FI, and VFI in early pregnancy as measured by the receiver operating characteristic curve to predict miscarriage before 12 gestational weeks in participants was 0.681, 0.876, 0.770, 0.720, 0.879, 0.771, 0.907, 0.592, respectively. The 3D-power Doppler ultrasound is a more comprehensive and sensitive method for evaluating endometrial receptivity. Endometrial volume, VI, FI, and VFI in the midluteal phase, as well as VI in early pregnancy, can be considered as predictive factors for recurrent miscarriage. Copyright © 2015. Published by Elsevier B.V.

Progesterone-induced miR-133a inhibits the proliferation of endometrial epithelial cells.

PubMed

Pan, J-L; Yuan, D-Z; Zhao, Y-B; Nie, L; Lei, Y; Liu, M; Long, Y; Zhang, J-H; Blok, L J; Burger, C W; Yue, L-M

2017-03-01

This study aimed to understand the role of miR-133a in progesterone actions, explore the regulative mechanism of the progesterone receptor, and investigate the effects of miR-133a on the progesterone-inhibited proliferation of mouse endometrial epithelial cells. The expression of miR-133a induced by progesterone was detected by quantitative real-time PCR both in vivo and in vitro. Ishikawa subcell lines stably transfected with progesterone receptor subtypes were used to determine the receptor mechanism of progesterone inducing miR-133a. Specific miR-133a mimics or inhibitors were transfected into mouse uteri and primary cultured endometrial epithelial cells to overexpress or downregulate the miR-133a. The roles of miR-133a in the cell cycle and proliferation of endometrial epithelial cells were analysed by flow cytometry and Edu incorporation analysis. The protein levels of cyclinD2 in uterine tissue sections and primary cultured endometrial epithelial cells were determined by immunohistochemistry and Western blot analysis. Progesterone could induce miR-133a expression in a PRB-dependent manner in endometrial epithelial cells. miR-133a inhibited endometrial epithelial cell proliferation by arresting cell cycle at the G 1 -S transition. Moreover, miR-133a acted as an inhibitor in downregulating cyclinD2 in endometrial epithelial cells. We showed for the first time that progesterone-induced miR-133a inhibited the proliferation of endometrial epithelial cells by downregulating cyclinD2. Our research indicated an important mechanism for progesterone inhibiting the proliferation of endometrial epithelial cells by inducing special miRNAs to inhibit positive regulatory proteins in the cell cycle. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Clusterin immunoexpression is associated with early stage endometrial carcinomas.

PubMed

Al-Maghrabi, Jaudah Ahmed; Butt, Nadeem Shafique; Anfinan, Nisrin; Sait, Khalid; Sait, Hesham; Bajouh, Osama; Khabaz, Mohamad Nidal

2016-05-01

Clusterin has anti-apoptotic, regeneration and migration stimulating effects on tumor cells. This study investigates the relation between clusterin expression and the clinicopathological parameters in endometrial carcinomas. Seventy one cases of previously diagnosed endometrial carcinoma (including 59 endometrioid adenocarcinoma, 9 serous adenocarcinoma, 1 clear cell adenocarcinoma, and 2 malignant mixed Mullerian tumor) and 30 tissue samples of non-cancerous endometrium (including 16 proliferative endometrium, 10 secretory endometrium and 4 endometrial polyps) were employed for clusterin detection using tissue microarrays and immunostaining. A total number of 23 (32.4%) cases were positive for clusterin immunostaining. Brown granular cytoplasmic expression of clusterin was detected in 33.9% of endometrioid adenocarcinomas, 22.2% papillary serous endometrial carcinomas. Three (10%) control cases showed granular cytoplasmic expression. Positive clusterin immunostaining was found more frequent in well differentiated and stage I endometrial carcinomas, showing significant statistical association (p-value=0.036 and p-value=0.002 respectively). Significant difference in clusterin expression was observed between tumor cases and control group (P-Value=0.019), i.e., endometrial carcinoma cases are more than four times likely to show positive clusterin immunostaining (odds ratio 4.313 with 95% confidence interval 1.184-15.701). This study did not find relation between clusterin expression and disease recurrence, survival or any of the other clinicopathological parameters in endometrial tumors. The results of our study confirms the diagnostic values of clusterin in supporting the diagnosis of endometrioid carcinoma. When clusterin is expressed in endometrial tumors, it is associated with lower stage. The correlation of clusterin with tumor stage suggests involvement of this molecule in endometrial tumor progression. Copyright © 2016 Elsevier GmbH. All rights reserved.

Enhancer of zeste homolog 2 blockade by RNA interference is implicated with inhibited proliferation, invasion and promoted apoptosis in endometrial carcinoma.

PubMed

Wang, Juan; Ai, Zhihong; Chen, Jing; Teng, Yincheng; Zhu, Jieping

2018-06-01

Endometrial carcinoma is the most common gynecological malignancy of the female genital tract worldwide (2012). Enhancer of zeste homolog 2 (EZH2), a critical component of the polycomb repressive complex 2, has been found to be associated with multiple biological processes and is overexpressed in multiple types of cancer. Previous studies have demonstrated that EZH2 is associated with endometrial carcinoma. The present study investigated the expression and biology function of EZH2 in endometrial cancer (EC). It was found that EZH2 levels were markedly increased in endometrial cancer tissues compared with that in adjacent normal tissues. EZH2 was significantly overexpressed in 3 separate endometrial cancer cell lines (Ishikawa, RL95-2 and HEC1-A) when compared with the normal endometrial cell line ESC. Additionally, small interfering RNA was used to investigate the role of EZH2 in endometrial carcinoma cell proliferation, and the results showed that EZH2 knockdown suppressed the proliferation of endometrial carcinoma cells in vitro . Furthermore, EZH2 knockdown induced apoptosis of human EC cells by promoting the expression of pro-apoptosis protein caspase 3, caspase 9, BCL2 associated X and decreasing the expression of anti-apoptosis protein Bcl-2. Finally, the present study demonstrated that EZH2 knockdown suppressed the invasion of EC cells through downregulation of the epithelial-mesenchymal transition. Collectively, these data demonstrate that EZH2 is frequently overexpressed in EC cells and its overexpression is associated with promoting the proliferation and invasion and decreasing the apoptosis of EC cells, suggesting that EZH2 may provide potential therapeutic targets for treatment of endometrial carcinoma.

Time trends in the incidence of hysterectomy-corrected overall, type 1 and type 2 endometrial cancer in Denmark 1978-2014.

PubMed

Faber, Mette Tuxen; Frederiksen, Kirsten; Jensen, Allan; Aarslev, Peter Bo; Kjaer, Susanne K

2017-08-01

To investigate time trends in the incidence of overall, type 1 and type 2 endometrial cancer in Denmark 1978-2014, correcting for hysterectomy. Based on the Danish Cancer Registry and the Danish National Patient Registry we calculated hysterectomy-corrected incidence rates of overall, type 1 and type 2 endometrial cancer. Separate analyses for women <55years (defined as pre- and perimenopausal age) and women aged ≥55years (defined as postmenopausal age) and analyses allowing for different time trends before and after the study period midyear 1996 were performed. Log-linear Poisson models were used to estimate annual percentage change (APC) in incidence with 95% confidence intervals (CI). The overall incidence of endometrial cancer decreased slightly from 1978 to 1995, but in the last two decades of the study period the incidence has been stable (APC=0.16; 95% CI: -0.19; 0.50). In the study period (1978-2014) type 1 endometrial cancer incidence decreased slightly (APC=-0.67; 95% CI:-0.83; -0.52), whereas the incidence of type 2 endometrial cancer increased substantially (APC=4.85; 95% CI: 4.47; 5.23). The decrease in type 1 endometrial cancer was most pronounced before 1996 in women younger than 55 years (APC=-2.79; 95% CI: -3.65; -1.91), while the largest increase in type 2 endometrial cancer was observed after 1996 (APC=6.42; 95% CI: 5.72; 7.12). Over a period of more than 35 years, the incidence of type 1 endometrial cancer decreased, mainly in pre- and perimenopausal women, while type 2 endometrial cancer incidence increased. Copyright © 2017 Elsevier Inc. All rights reserved.

Coffee consumption and risk of endometrial cancer: a prospective study in Japan.

PubMed

Shimazu, Taichi; Inoue, Manami; Sasazuki, Shizuka; Iwasaki, Motoki; Kurahashi, Norie; Yamaji, Taiki; Tsugane, Shoichiro

2008-11-15

Coffee has been proposed to decrease the circulating insulin and estrogen levels, which are related to the development of endometrial cancer. However, few studies have prospectively assessed the association between coffee consumption and endometrial cancer. We conducted a population-based prospective cohort study in 53,724 Japanese women aged 40-69 years with no history of cancer at baseline in 1990-1994. We used Cox proportional hazards regression analysis to estimate the hazard ratio (HR) and 95% confidence interval (CI) of endometrial cancer incidence in relation to coffee consumption. All reported p values are 2-tailed. During the 15-year follow-up period, we documented 117 cases of endometrial cancer. Coffee consumption was significantly associated with a decreased risk of endometrial cancer. After adjustment for age, study area, body mass index, menopausal status, age at menopause for postmenopausal women, parity, use of exogenous female hormones, smoking status and by consumption of green vegetables, beef, pork and green tea, the multivariate HRs (95% CI) of endometrial cancer in women who drank coffee /=3 cups/day were 1.00, 0.97 (0.56-1.68), 0.61 (0.39-0.97) and 0.38 (0.16-0.91), respectively (p for trend = 0.007). In contrast, green tea consumption was not significantly associated with a reduced risk of endometrial cancer (p for trend = 0.22). The inverse association between coffee consumption and risk of endometrial cancer was consistently observed in subgroup analyses stratified by potential confounders. Coffee consumption may be associated with a decreased risk of endometrial cancer. (c) 2008 Wiley-Liss, Inc.

Endometrial biopsy

MedlinePlus

... Names Biopsy - endometrium Images Pelvic laparoscopy Female reproductive anatomy Endometrial biopsy Uterus Endometrial biopsy References Beard JM, Osborn J. Common office procedures. In: Rakel RE, Rakel DP, eds. Textbook of Family Medicine . 9th ed. Philadelphia, PA: Elsevier ...

General Information About Endometrial Cancer

MedlinePlus

... Research Endometrial Cancer Treatment (PDQ®)–Patient Version General Information About Endometrial Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

Endometrial cancer - reduce to the minimum. A new paradigm for adjuvant treatments?

PubMed Central

2011-01-01

Background Up to now, the role of adjuvant radiation therapy and the extent of lymph node dissection for early stage endometrial cancer are controversial. In order to clarify the current position of the given adjuvant treatment options, a systematic review was performed. Materials and methods Both, Pubmed and ISI Web of Knowledge database were searched using the following keywords and MESH headings: "Endometrial cancer", "Endometrial Neoplasms", "Endometrial Neoplasms/radiotherapy", "External beam radiation therapy", "Brachytherapy" and adequate combinations. Conclusion Recent data from randomized trials indicate that external beam radiation therapy - particularly in combination with extended lymph node dissection - or radical lymph node dissection increases toxicity without any improvement of overall survival rates. Thus, reduced surgical aggressiveness and limitation of radiotherapy to vaginal-vault-brachytherapy only is sufficient for most cases of early stage endometrial cancer. PMID:22118369

[Pitfalls in the histopathological diagnostics of endometrial carcinoma and its precursors : Clinically relevant differential diagnoses, avoidance of false positive diagnoses].

PubMed

Kommoss, F; Lax, S F

2016-11-01

Making an incorrect histopathological diagnosis of an endometrial lesion may lead to unwanted loss of fertility and therapy-associated morbidity; therefore, endometrial carcinomas need to be correctly typed and differentiated from hyperplastic precursors, benign lesions and artifacts. Typical diagnostic pitfalls are described in this article. Misdiagnosing endometrial lesions can be avoided by paying thorough attention to gross as well as microscopic features and by taking crucial differential diagnoses into consideration. These are, in particular, well-differentiated endometrioid adenocarcinoma of the endometrium versus atypical endometrial hyperplasia, myoinvasive endometrioid adenocarcinoma versus atypical polypoid adenomyoma and endometrioid carcinoma versus serous carcinoma of the endometrium with a predominantly glandular pattern. It is also important to consider the possibility of a false positive diagnosis of atypical endometrial hyperplasia or carcinoma in cases of biopsy-induced artifacts.

Expression and function of activin receptors in human endometrial adenocarcinoma cells.

PubMed

Tanaka, Tetsuji; Toujima, Saori; Otani, Tsutomu; Minami, Sawako; Yamoto, Mareo; Umesaki, Naohiko

2003-09-01

Menstrual cycle-dependent expressions of activin A in normal human endometrial tissues have been reported. Expression of activin receptor mRNAs and increased activin A production were also observed in human endometrial adenocarcinoma tissues, suggesting that activin A might enhance cell proliferation and inhibit apoptotic signaling in endometrial cancer cells. In this study, we have examined the effects of activin A on cell proliferation, anticancer drug-induced apoptosis and Fas-mediated apoptosis in 3 differentiated human endometrial adenocarcinoma cell lines, namely HEC-1, HHUA and Ishikawa. Flow cytometric analyses revealed moderate expressions of all 4 types of activin receptor subunits on the cell surfaces of the 3 cell lines. The proliferations of the 3 endometrial cancer cells were completely unaffected by activin A, whereas it suppressed the cell proliferation of a human ovarian endometrioid adenocarcinoma cell line, OVK-18, in a dose-dependent manner. Moreover, activin A did not affect the apoptotic changes in the 3 endometrial adenocarcinoma cells treated with 4 different anticancer drugs, namely CDDP, paclitaxel, etoposide and SN38. The apoptotic changes in HHUA cells treated with anti-Fas IgM were also unaffected by activin A. These results indicate that the increased activin A production in human endometrial adenocarcinoma tissues in vivo may not stimulate carcinoma cell proliferation or inhibit apoptotic signaling in carcinoma cells. Insensitivity to the usual growth suppression signals induced by activin A might be one of the mechanisms of immortality of human endometrial adenocarcinoma cells.

New diagnostic reporting format for endometrial cytology based on cytoarchitectural criteria

PubMed Central

Yanoh, K; Norimatsu, Y; Hirai, Y; Takeshima, N; Kamimori, A; Nakamura, Y; Shimizu, K; Kobayashi, T K; Murata, T; Shiraishi, T

2009-01-01

Objective: The aim of this study was to develop a new reporting format for endometrial cytology that would standardize the diagnostic criteria and the terminology used for reporting. Methods: In previous studies, cytoarchitectural criteria were found to be useful for the cytological assessment of endometrial lesions. To apply these criteria, an appropriate cytological specimen is imperative. In this article, the requirements of an adequate endometrial cytological specimen for the new diagnostic criteria are first discussed. Then, the diagnostic criteria, standardized on a combination of conventional and cytoarchitectural criteria, are presented. Third, terminology that could be used, not only for reporting the histopathological diagnosis, but also for providing better guidance for the gynaecologist to determine further clinical action, is introduced. The proposed reporting format was investigated using endometrial cytology of 58 cases that were cytologically underestimated or overestimated compared to the histopathological diagnosis made on the subsequent endometrial biopsy or surgical specimens. Results: Of the 58 cases, 12 were reassessed as being unsatisfactory for evaluation. Among the remaining 46 cases, 25 of the 27 cases, which had been underestimated and subsequently diagnosed as having endometrial carcinoma or a precursor stage on histopathological examination,were reassessed as recommended for endometrial biopsy. On the other hand, 19 cases overestimated by cytology were all reassessed as not requiring biopsy. Conclusions: The reporting format for endometrial cytology proposed in this article may improve diagnostic accuracy and reduce the number of patients managed inappropriately. PMID:18657157

Development of In Vitro Embryo Production System Using Collagen Matrix Gel Attached with Vascular Endothelial Growth Factor Derived from Interleukin-1 Beta-Treated Porcine Endometrial Tissue.

PubMed

Han, Hye-In; Lee, Sang-Hee; Park, Choon-Keun

2017-07-01

The aim of this study was to establish an embryo culture system using collagen gel attached with vascular endothelial growth factor (VEGF) derived from interleukin-1 beta (IL-1β)-treated endometrial tissues from pigs. Endometria were separated from the porcine uterus at the follicular phase of the estrous cycle and were cultured with IL-1β. The collagen gels coincubated with IL-1β-treated endometria (C, without endometrial tissue; CE, with endometrial tissue; and CEI, IL-1β-treated endometrial tissue) were used for embryo culture. We found that, compared with the comparable figures in the control group, prostaglandin synthase-2 (PTGS-2) mRNA was increased in IL-1β-treated endometrial tissue (p < 0.05). The VEGF protein was not observed in collagen gel coincubated without endometrial tissue (C); however, it was detected in collagen gels coincubated with endometrial tissue (CE and CEI). The embryo cleavage rates and blastocyst formation did not differ among the treatment groups. The proportion of blastocysts did not differ among the groups. However, the number of blastocyst cells was significantly (p < 0.05) higher in the CEI group than in the other groups. These results clarify the effects of the intrauterine environment on preimplantation embryos and may be useful in research on the effects of extracellular matrix- and cytokine-treated endometrial tissue on embryo development.

Curcumin exhibits anti-tumor effect and attenuates cellular migration via Slit-2 mediated down-regulation of SDF-1 and CXCR4 in endometrial adenocarcinoma cells.

PubMed

Sirohi, Vijay Kumar; Popli, Pooja; Sankhwar, Pushplata; Kaushal, Jyoti Bala; Gupta, Kanchan; Manohar, Murli; Dwivedi, Anila

2017-06-01

Although curcumin shows anti-proliferative and anti-inflammatory activities in various cancers, the effect of curcumin on cellular migration in endometrial adenocarcinoma cells remains to be understood. The current investigation was aimed to explore the anti-proliferative and anti-migratory effects of curcumin and its mechanism of action in endometrial cancer cells. Our in-vitro and in-vivo experimental studies showed that curcumin inhibited the proliferation of endometrial cancer cells and suppressed the tumor growth in Ishikawa xenograft mouse model. Curcumin induced ROS-mediated apoptosis in endometrial cancer cells. Curcumin suppressed the migration rate of Ishikawa and Hec-1B cells as analyzed by scratch wound assay. In transwell migration studies, knock down of Slit-2 reversed the anti-migratory effect of curcumin in these cell lines. Curcumin significantly up-regulated the expression of Slit-2 in Ishikawa, Hec-1B and primary endometrial cancer cells while it down-regulated the expression of stromal cell-derived factor-1 (SDF-1) and CXCR4 which in turn, suppressed the expression of matrix metallopeptidases (MMP) 2 and 9, thus attenuating the migration of endometrial cancer cells. In summary, we have demonstrated that curcumin has inhibitory effect on cellular migration via Slit-2 mediated down-regulation of CXCR4, SDF-1, and MMP2/MMP9 in endometrial carcinoma cells. These findings helped explore the role of Slit-2 in endometrial cancer cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Oral Progestogens Versus Levonorgestrel-Releasing Intrauterine System for Treatment of Endometrial Intraepithelial Neoplasia.

PubMed

Marnach, Mary L; Butler, Kristina A; Henry, Michael R; Hutz, Catherine E; Langstraat, Carrie L; Lohse, Christine M; Casey, Petra M

2017-04-01

Limited therapeutic guidelines exist regarding medical therapy, ideal dosing, duration of therapy, or recommendations for timing of endometrial reassessment for women with endometrial intraepithelial neoplasia (EIN) who desire fertility preservation or who are not optimal surgical candidates. We aimed to determine the effectiveness of oral progestogens (OP) versus the levonorgestrel-releasing intrauterine system (LNG IUS) in the medical treatment of EIN. We retrospectively identified women with EIN at our institution from 2007 through 2014 and compared the outcomes of those treated with OP versus LNG IUS. Among 390 women, 296 were initially treated with OP and 94 with LNG IUS. Baseline characteristics of the patient groups were comparable, except for higher median body mass index in the LNG IUS group versus the OP group (37 kg/m 2 vs. 31 kg/m 2 ; p < 0.001). Among 332 women with follow-up endometrial biopsies (263 OP and 69 LNG IUS), EIN subcategory 1 (benign endometrial hyperplasia) resolved in 83% and 87% of patients, respectively (p = 0.31). Rates of resolution of EIN subcategory 2 (endometrial intraepithelial neoplasia) were also similar between groups (68% vs. 62%; p = 0.82). In women with EIN subcategory 3 (endometrial adenocarcinoma), 22% of those using LNG IUS and one of two women treated with OP had resolution of disease as of last follow-up. OP and LNG IUS offer similar endometrial protection for women with EIN. LNG IUS offers convenience, minimal adverse effects, reversibility, and long-term endometrial protection.

Treatment of Low-Risk Endometrial Cancer and Complex Atypical Hyperplasia With the Levonorgestrel-Releasing Intrauterine Device.

PubMed

Pal, Navdeep; Broaddus, Russell R; Urbauer, Diana L; Balakrishnan, Nyla; Milbourne, Andrea; Schmeler, Kathleen M; Meyer, Larissa A; Soliman, Pamela T; Lu, Karen H; Ramirez, Pedro T; Ramondetta, Lois; Bodurka, Diane C; Westin, Shannon N

2018-01-01

To assess efficacy of the levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of complex atypical hyperplasia or low-grade endometrial cancer. This retrospective case series included all patients treated with the LNG-IUD for complex atypical hyperplasia or early-grade endometrial cancer from January 2003 to June 2013. Response rates were calculated and the association of response with clinicopathologic factors, including age, body mass index, and uterine size, was determined. Forty-six patients diagnosed with complex atypical hyperplasia or early-grade endometrial cancer were treated with the LNG-IUD. Of 32 evaluable patients at the 6-month time point, 15 had complex atypical hyperplasia (47%), nine had G1 endometrial cancer (28%), and eight had grade 2 endometrial cancer (25%). Overall response rate was 75% (95% CI 57-89) at 6 months; 80% (95% CI 52-96) in complex atypical hyperplasia, 67% (95% CI 30-93) in grade 1 endometrial cancer, and 75% (CI 35-97) in grade 2 endometrial cancer. Of the clinicopathologic features evaluated, there was a trend toward the association of lack of exogenous progesterone effect in the pathology specimen with nonresponse to the IUD (P=.05). Median uterine diameter was 1.3 cm larger in women who did not respond to the IUD (P=.04). Levonorgestrel-releasing IUD therapy for the conservative treatment of complex atypical hyperplasia or early-grade endometrial cancer resulted in return to normal histology in a majority of patients.

Obesity and age at diagnosis of endometrial cancer.

PubMed

Nevadunsky, Nicole S; Van Arsdale, Anne; Strickler, Howard D; Moadel, Alyson; Kaur, Gurpreet; Levitt, Joshua; Girda, Eugenia; Goldfinger, Mendel; Goldberg, Gary L; Einstein, Mark H

2014-08-01

Obesity is an established risk factor for development of endometrial cancer. We hypothesized that obesity might also be associated with an earlier age at endometrial cancer diagnosis, because mechanisms that drive the obesity-endometrial cancer association might also accelerate tumorigenesis. A retrospective chart review was conducted of all cases of endometrial cancer diagnosed from 1999 to 2009 at a large medical center in New York City. The association of body mass index (BMI) with age at endometrial cancer diagnosis, comorbidities, stage, grade, and radiation treatment was examined using analysis of variance and linear regression. Overall survival by BMI category was assessed using Kaplan-Meier method and the log-rank test. A total of 985 cases of endometrial cancer were identified. The mean age at endometrial cancer diagnosis was 67.1 years (±11.9 standard deviation) in women with a normal BMI, whereas it was 56.3 years (±10.3 standard deviation) in women with a BMI greater than 50. Age at diagnosis of endometrioid-type cancer decreased linearly with increasing BMI (y=67.89-1.86x, R=0.049, P<.001). This association persisted after multivariable adjustment (R=0.181, P<.02). A linear association between BMI and age of nonendometrioid cancers was not found (P=.12). There were no differences in overall survival by BMI category. Obesity is associated with earlier age at diagnosis of endometrioid-type endometrial cancers. Similar associations were not, however, observed with nonendometrioid cancers, consistent with different pathways of tumorigenesis. II.

Thicker endometrial linings are associated with better IVF outcomes: a cohort of 6331 women.

PubMed

Holden, Emily C; Dodge, Laura E; Sneeringer, Rita; Moragianni, Vasiliki A; Penzias, Alan S; Hacker, Michele R

2017-06-18

Our objective was to determine if a correlation exists between endometrial thickness measured on the day of ovulation trigger during an in vitro fertilization (IVF) cycle and pregnancy outcomes among non-cancelled cycles. We performed a retrospective cohort study looking at 6331 women undergoing their first, fresh autologous IVF cycle from 1 May 2004 to 31 December 2012 at Boston IVF (Waltham, MA). Our primary outcome was the risk ratio (RR) of live birth and positive β-hCG. We found that thicker endometrial linings were associated with positive β-hCG and live birth rates. For each additional millimetre of endometrial thickness, we found a statistically significant increased risk of positive β-hCG (adjusted RR: 1.14; 95% CI: 1.09-1.18) and live birth (RR: 1.08; 95% CI: 1.05-1.11). There was no association between endometrial thickness and miscarriage (RR: 0.99; 95% CI: 0.91-1.07). Similar results were seen when categorizing endometrial thickness. Compared with an endometrial thickness >7 to <11 mm, the likelihood of a live birth was significantly higher for an endometrial thickness ≥11 mm (adjusted RR: 1.23; 95% CI: 1.11-1.37) and significantly lower for the ≤7 mm group (adjusted RR: 0.64; 95% CI: 0.45-0.90). In conclusion, thicker endometrial linings were associated with increased pregnancy and live birth rates.

Roles of the insulinlike growth factor family in nonpregnant human endometrium and at the decidual: trophoblast interface.

PubMed

Giudice, L C; Irwin, J C

1999-01-01

The insulinlike growth factor (IGF) family is believed to be important in endometrial development during the menstrual cycle and in the process of implantation. The mitogenic, differentiative, and antiapoptotic properties of the IGFs and their binding proteins, as well as their spatial and temporal expression in cycling endometrium, suggest that they may participate in endometrial growth, differentiation, apoptosis, and perhaps angiogenesis. IGFBP proteases, which increase IGF bioavailability, have been localized to endometrial stromal cells and to the human cytotrophoblast and likely play important roles in endometrial, decidual, and trophoblast physiology. IGFBP-1 is a major protein product of nonpregnant endometrium during the mid-late secretory phase and occurs in abundance in decidua. Its roles as an IGF-binding protein and as a trophoblast integrin ligand suggest that it may have multiple roles in endometrial development and in interactions between the decidua and the invading trophoblast. Recent evidence suggests that it may have a role in the process of shallow implantation in the clinical disorder of preclampsia. In contrast to knowledge about the roles of IGF peptides, IGFBP proteases, and IGFBPs in normal endometrial development and early human pregnancy, little information is available regarding this family in abnormal endometrial development, in occult endometrial defects, and in uterine receptivity and nonreceptivity.

Higher Prevalence of Endometrial Polyps in Infertile Patients with Endometriosis.

PubMed

Zhang, Ya-Nan; Zhang, You-Sheng; Yu, Qian; Guo, Zi-Zhen; Ma, Jin-Long; Yan, Lei

2018-06-07

To study whether infertile patients with endometriosis have a higher prevalence of endometrial polyps, and to clarify the characteristics of the pathology of combined polyps. Infertile patients who had undergone both hysteroscopy and laparoscopy in Reproductive Hospital Affiliated with Shandong University from January 2014 to May 2017 were enrolled. Patients with and without endometriosis, diagnosed by laparoscopy, were staged and included in the study group and control group, respectively, and the prevalence of polyps was compared. The pathological types of endometrial polyps were analyzed. A total of 414 cases were enrolled in the study group and 3,048 cases in the control group; polyps were diagnosed, with endoscopy, in 1,107 patients. Endometrial polyps were detected by hysteroscopy in 47.83% of the endometriosis group and 29.82% of the control group. The prevalence of endometrial polyps was significantly higher in the endometriosis group than in the control group (p < 0.001) but not significantly different between stages of endometriosis (p = 0.580). The pathological diagnosis included 899 endometrial polyps and 208 polypoid hyperplasia; 66.5% of endometrial polyps were combined with simple hyperplasia. The infertile patients with endometriosis had a higher prevalence of endometrial polyps, and those polyps are often combined with simple hyperplasia. © 2018 S. Karger AG, Basel.

Dietary fat intake and endometrial cancer risk

PubMed Central

Zhao, Jing; Lyu, Chen; Gao, Jian; Du, Li; Shan, Boer; Zhang, Hong; Wang, Hua-Ying; Gao, Ying

2016-01-01

Abstract Since body fatness is a convincing risk factor for endometrial cancer, dietary fat intake was speculated to be associated with endometrial cancer risk. However, epidemiological studies are inconclusive. We aimed to conduct a meta-analysis to assess the associations between dietary fat intake and endometrial cancer risk. We searched the PubMed, Embase, and Web of science databases updated to September 2015. In total, 7 cohort and 14 case–control studies were included. Pooled analysis of case–control studies suggested that endometrial cancer risk was significantly increased by 5% per 10% kilocalories from total fat intake (P=0.02) and by 17% per 10 g/1000 kcal of saturated fat intake (P < 0.001). Summary of 3 cohort studies showed significant inverse association between monounsaturated fatty acids and endometrial cancer risk (odds ratio = 0.84, 95% confidence interval = 0.73–0.98) with a total of 524583 participants and 3503 incident cases. No significant associations were found for polyunsaturated fatty acids and linoleic acid. In conclusion, positive associations with endometrial cancer risk were observed for total fat and saturated fat intake in the case–control studies. Results from the cohort studies suggested higher monounsaturated fatty acids intake was significantly associated with lower endometrial cancer risk. PMID:27399120

Postmenopausal bleeding: value of imaging.

PubMed

Reinhold, Caroline; Khalili, Ida

2002-05-01

Endovaginal sonography in combination with HSG is an effective screening tool in evaluating patients with postmenopausal bleeding. Endovaginal sonography is highly sensitive for detecting endometrial carcinoma and can identify patients at low risk for endometrial disease obviating the need for endometrial sampling in this subgroup of patients. In patients with abnormal findings at sonography, a detailed morphologic analysis can be used to determine which patients can undergo blind endometrial sampling successfully versus those who would benefit from hysteroscopic guidance. In patients in whom endovaginal sonography and HSG are inadequate, MRI may provide additional information on the appearance of the endometrium, particularly in patients in whom endometrial sampling is difficult (eg, patients with cervical stenosis).

Tamoxifen-Dependent Induction of AGR2 Is Associated with Increased Aggressiveness of Endometrial Cancer Cells.

PubMed

Hrstka, Roman; Podhorec, Jan; Nenutil, Rudolf; Sommerova, Lucia; Obacz, Joanna; Durech, Michal; Faktor, Jakub; Bouchal, Pavel; Skoupilova, Hana; Vojtesek, Borivoj

2017-05-28

Tamoxifen treatment in breast cancer patients is associated with increased risk of endometrial malignancies. Significantly, higher AGR2 expression was found in endometrial cancers that developed in women previously treated with tamoxifen compared to those who had not been exposed to tamoxifen. An association of elevated AGR2 level with myometrial invasion occurrence and invasion depth was also found. In vitro analyses identified a stimulatory effect of AGR2 on cellular proliferation. Although adverse tamoxifen effects on endometrial cells remain elusive, our work identifies elevated AGR2 as a candidate tamoxifen-dependent mechanism of action responsible for increased incidence of endometrial cancer.

Moving forward with actionable therapeutic targets and opportunities in endometrial cancer: NCI clinical trials planning meeting report on identifying key genes and molecular pathways for targeted endometrial cancer trials

PubMed Central

MacKay, Helen J.; Levine, Douglas A.; Bae-Jump, Victoria L.; Bell, Daphne W.; McAlpine, Jessica N.; Santin, Alessandro; Fleming, Gini F.; Mutch, David G.; Nephew, Kenneth P.; Wentzensen, Nicolas; Goodfellow, Paul J.; Dorigo, Oliver; Nijman, Hans W.; Broaddus, Russell; Kohn, Elise C.

2017-01-01

The incidence and mortality rates from endometrial cancer are increasing. There have been no new drugs approved for the treatment of endometrial cancer in decades. The National Cancer Institute, Gynecologic Cancer Steering Committee identified the integration of molecular and/or histologic stratification into endometrial cancer management as a top strategic priority. Based on this, they convened a group of experts to review the molecular data in this disease. Here we report on the actionable opportunities and therapeutic directions identified for incorporation into future clinical trials. PMID:29137450

Progesterone potentiates the growth inhibitory effects of calcitriol in endometrial cancer via suppression of CYP24A1.

PubMed

Bokhari, Amber A; Lee, Laura R; Raboteau, Dewayne; Turbov, Jane; Rodriguez, Isabel V; Pike, John Wesley; Hamilton, Chad A; Maxwell, George Larry; Rodriguez, Gustavo C; Syed, Viqar

2016-11-22

Here, we evaluated the expression of CYP24A1, a protein that inactivates vitamin D in tissues. CYP24A1 expression was increased in advanced-stage endometrial tumors compared to normal tissues. Similarly, endometrial cancer cells expressed higher levels of CYP24A1 than immortalized endometrial epithelial cells. RT-PCR and Western blotting were used to examine CYP24A1 mRNA and protein levels in endometrial cancer cells after 8, 24, 72, and 120 h of exposure to progesterone, progestin derivatives and calcitriol, either alone or in combination. Progestins inhibited calcitriol-induced expression of CYP24A1 and splice variant CYP24SV mRNA and protein in cancer cells. Furthermore, actinomycin D, but not cycloheximide, blocked calcitriol-induced CYP24A1 splicing. siRNA-induced knockdown of CYP24A1 expression sensitized endometrial cancer cells to calcitriol-induced growth inhibition. These data suggest that CYP24A1 overexpression reduces the antitumor effects of calcitriol in cancer cells and that progestins may be beneficial for maintaining calcitriol's anti-endometrial cancer activity.

Cigarette Smoke Increases Progesterone Receptor and Homeobox A10 Expression in Human Endometrium and Endometrial Cells: A Potential Role in the Decreased Prevalence of Endometrial Pathology in Smokers1

PubMed Central

Zhou, Yuping; Jorgensen, Elisa M.; Gan, Ye; Taylor, Hugh S.

2011-01-01

Cigarette smoking has long been tied to a multitude of poor health outcomes; however, in reproductive biology, smoking has shown several unintuitive findings. Smoking is associated with significantly decreased rates of endometriosis and endometrial cancer. Here, we show that treatment with cigarette smoke extract leads to increased mRNA and protein expression of homeobox A10 (HOXA10) and progesterone receptor (PGR) as well as more rapid decidualization of endometrial stromal cells in vitro. In vivo, mice exposed to cigarette smoke similarly showed increased expression of HOXA10 and PGR in the endometrium. Both HOXA10 and PGR drive endometrial differentiation and are suppressed in endometrial tumors and in endometriosis. The increased expression found upon exposure to cigarette smoke may provide a protective effect, mediating the decreased incidence of endometrial disease among smokers. This mechanism contrasts with the accepted paradigm that the effects of smoking on the uterus are secondary to ovarian alterations rather than direct effects on endometrium as demonstrated here. PMID:21325691

H19 promotes endometrial cancer progression by modulating epithelial-mesenchymal transition

PubMed Central

Zhao, Le; Li, Zhen; Chen, Wei; Zhai, Wen; Pan, Jingjing; Pang, Huan; Li, Xu

2017-01-01

Endometrial cancer is one of the most common types of gynecological malignancy worldwide. Novel biomarkers and therapeutic targets are imperative for improving patients' survival. Previous studies have suggested the long non-coding RNA H19 as a potential cancer biomarker. To investigate the role of H19 in endometrial cancer, the present study examined the expression pattern of H19 in endometrial cancer tissues by quantitative polymerase chain reaction, and characterized its function in the endometrial cancer cell line via knocking down its expression with small interfering RNAs. It was found that H19 level was significantly higher in tumor tissues than in paratumoral tissues. Knockdown of H19 did not affect the growth rate of HEC-1-B endometrial cancer cells, but significantly suppressed in vitro migration and invasion of HEC-1-B cells. Furthermore, H19 downregulation decreased Snail level and increased E-cadherin expression without affecting vimentin level, indicating partial reversion of epithelial-mesenchymal transition (EMT). The present findings suggested that H19 contributed to the aggressiveness of endometrial cancer by modulating EMT process. PMID:28123568

Endometrial Cancer Screening (PDQ®)—Health Professional Version

Cancer.gov

Endometrial cancer screening by ultrasonography or tissue sampling is not supported by current evidence, but most cases are diagnosed at early stage. Get detailed information about potential harms of endometrial cancer screening in this summary for clinicians.

Study establishes basis for genomic classification of endometrial cancers

Cancer.gov

A comprehensive genomic analysis of nearly 400 endometrial tumors suggests that certain molecular characteristics – such as the frequency of mutations – could complement current pathology methods and help distinguish between principal types of endometrial

Endometrial Cancer Prevention (PDQ®)—Patient Version

Cancer.gov

Endometrial cancer prevention strategies include avoiding risk factors when possible and increasing protective factors that may help prevent cancer. Learn more about known risk and protective factors and approaches to prevent endometrial cancer in this expert-reviewed summary.

Endometrial Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Endometrial cancer is usually diagnosed at an early stage and can be treated with surgery. Learn about the symptoms, diagnosis, prognosis, staging, and treatment for early- and advanced-stage endometrial cancer in this expert-reviewed summary.

Robot-assisted laparoscopic adenomyomectomy of adenomyotic nodule implanted in the uterine endometrium manifesting as endometrial cancer: a case report and literature review.

PubMed

Jeon, J H; Jeong, K; Moon, H S

2017-01-01

Thickened uterine endometrium with abnormal uterine bleeding highly suggests endometrial hyperplasia or endometrial carcinoma. A case of 35-year-old nulliparous woman came to our department with endometrial mass manifesting as endometrial cancer. Transrectal ultrasonography and magnetic resonance imaging (MRI) showed an 8x6 cm multicystic, ill-defined mass compacted at the uterine endometrium, the anterior wall of the uterus, and 3x3 cm heterogenous mass at the left adnexa. The edometrial mass showed multiple septations with enhancement and low-signal intensity on T2-weighted images. After endometrial biopsy was done and simple hyperplasia without atypia was observed at the histopathologic finding, the patient underwent robot-assisted laparoscopy and diagnosed as adenomyoma at the frozen pathology. After adenomyomectomy, permanent pathologic analysis revealed the same result and she recovered without any complications and responded well to gonadotropin-releasing hormone (GnRH) agonist therapy.

Evaluation of endometrial cancer epidemiology in Romania.

PubMed

Bohîlțea, R E; Furtunescu, F; Dosius, M; Cîrstoiu, M; Radoi, V; Baroș, A; Bohîlțea, L C

2015-01-01

Endometrial cancer represents the most frequent gynecological malignant affection in the developed countries, in which the incidence of cervical cancer has significantly decreased due to the rigorous application of screening methods and prophylaxis. According to its frequency, endometrial cancer is situated on the fourth place in the category of women's genital-mammary malignant diseases, after breast, cervical and ovarian cancer in Romania. The incidence and mortality rates due to endometrial cancer have registered an increasing trend worldwide and also in Romania, a significant decrease of the age of appearance for the entire endometrial pathology sphere being noticed. At the national level, the maximum incidence is situated between 60 and 64 years old, the mortality rate of the women under 65 years old being high in Romania. The study evaluates endometrial cancer, from an epidemiologic point of view, at the national level compared to the international statistic data.

Androgens and endometrium: New insights and new targets.

PubMed

Simitsidellis, Ioannis; Saunders, Philippa T K; Gibson, Douglas A

2018-04-15

Androgens are synthesised in both the ovary and adrenals in women and play an important role in the regulation of female fertility, as well as in the aetiology of disorders such as polycystic ovarian syndrome, endometriosis and endometrial cancer. The endometrium is an androgen target tissue and the impact of AR-mediated effects has been studied using human endometrial tissue samples and rodent models. In this review we highlight recent evidence that endometrial androgen biosynthesis and intracrine action is important in preparation of a tissue microenvironment that can support implantation and establishment of pregnancy. The impact of androgens on endometrial cell proliferation, in repair of the endometrial wound at the time of menstruation and in endometrial disorders is discussed. Future directions for research focused on AR function as a therapeutic target are considered. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

International Endometrial Tumor Analysis (IETA) terminology in women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm: agreement and reliability study.

PubMed

Sladkevicius, P; Installé, A; Van Den Bosch, T; Timmerman, D; Benacerraf, B; Jokubkiene, L; Di Legge, A; Votino, A; Zannoni, L; De Moor, B; De Cock, B; Van Calster, B; Valentin, L

2018-02-01

To estimate intra- and interrater agreement and reliability with regard to describing ultrasound images of the endometrium using the International Endometrial Tumor Analysis (IETA) terminology. Four expert and four non-expert raters assessed videoclips of transvaginal ultrasound examinations of the endometrium obtained from 99 women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm but without fluid in the uterine cavity. The following features were rated: endometrial echogenicity, endometrial midline, bright edge, endometrial-myometrial junction, color score, vascular pattern, irregularly branching vessels and color splashes. The color content of the endometrial scan was estimated using a visual analog scale graded from 0 to 100. To estimate intrarater agreement and reliability, the same videoclips were assessed twice with a minimum of 2 months' interval. The raters were blinded to their own results and to those of the other raters. Interrater differences in the described prevalence of most IETA variables were substantial, and some variable categories were observed rarely. Specific agreement was poor for variables with many categories. For binary variables, specific agreement was better for absence than for presence of a category. For variables with more than two outcome categories, specific agreement for expert and non-expert raters was best for not-defined endometrial midline (93% and 96%), regular endometrial-myometrial junction (72% and 70%) and three-layer endometrial pattern (67% and 56%). The grayscale ultrasound variable with the best reliability was uniform vs non-uniform echogenicity (multirater kappa (κ), 0.55 for expert and 0.52 for non-expert raters), and the variables with the lowest reliability were appearance of the endometrial-myometrial junction (κ, 0.25 and 0.16) and the nine-category endometrial echogenicity variable (κ, 0.29 and 0.28). The most reliable color Doppler variable was color score (mean weighted κ, 0.77 and 0.69). Intra- and interrater agreement and reliability were similar for experts and non-experts. Inter- and intrarater agreement and reliability when using IETA terminology were limited. This may have implications when assessing the association between a particular ultrasound feature and a specific histological diagnosis, because lack of reproducibility reduces the reliability of the association between a feature and the outcome. Future studies should investigate whether using fewer categories of variable or offering practical training could improve agreement and reliability. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

"Pseudomyxoma Endometrii": Endometrial Deposition of Acellular Mucin from a Low-Grade Appendiceal Mucinous Neoplasm as a Rare Mimic of Myxoid Uterine Tumors.

PubMed

Shaw, Kristin C; Kokh, Dina; Ioffe, Olga B; Staats, Paul N

2015-07-01

Low-grade appendiceal mucinous neoplasms (LAMNs) are commonly associated with deposition of mucin, with or without admixed low-grade epithelium, on peritoneal surfaces (pseudomyxoma peritonei). We describe a very rare presentation of LAMN as extensive mucin deposition in the endometrium of a 43-yr-old woman initially mistaken for a primary uterine myxoid neoplasm. The patient underwent endometrial curettage that demonstrated abundant myxoid/mucoid material interspersed with small vessels, bland eosinophilic spindled cells, scattered foci of typical endometrial stroma, and occasional endometrioid glands. The endometrial stroma was positive for CD10, and the eosinophilic spindled cells were positive for actin. The lesion was interpreted as "myxoid/mucinous neoplasm, most likely of smooth muscle/endometrial stromal origin." Subsequent laparotomy revealed peritoneal mucin in the anterior cul-de-sac and a dilated appendix. Pathologic review confirmed appendiceal LAMN and multifocal peritoneal mucinosis. The uterus contained scant residual mucoid material. On review of all pathologic material at our institution, the endometrial lesion was consistent with organizing mucin derived from the LAMN with entrapped benign endometrium. "Pseudomyxoma endometrii" is readily mistaken for a primary uterine myxoid neoplasm, particularly myxoid endometrial stromal tumor. A key to diagnosis is recognition that the material is mucin rather than myxoid stroma. This is evidenced by the absence of embedded stromal cells and presence of myofibroblastic, vascular, and macrophage infiltration associated with organization. Epithelium containing goblet cells is an important clue if present. The presence of rare endometrial glands within the endometrial stroma suggests that the latter is entrapped rather than neoplastic.

S100A4 Mediates Endometrial Cancer Invasion and is a Target of TGF-β1 Signaling

PubMed Central

Xie, Ran; Schlumbrecht, Matthew; Shipley, Gregory L.; Xie, Susu; Bassett, Roland L.; Broaddus, Russell R.

2009-01-01

The molecular mechanisms of endometrial cancer invasion are poorly understood. S100A4, also known as FSP1 (fibroblast specific protein 1), has long been known to be a molecular marker of fibrosis in a variety of different fibrotic diseases of the lungs, liver, kidney, and heart. We demonstrate here that increased expression of S100A4 is associated with advanced stage endometrial cancer and decreased recurrence free survival. To verify the essential role of S100A4 in invasiveness of endometrial cancer, S100A4 expression was down-regulated by RNAi in HEC-1A cells, which resulted in undetectable S100A4 protein and significantly decreased migration and invasion. Due to the established connection between TGF-β1 and S100A4 induction in experimental models of kidney and liver fibrosis, we next examined whether TGF-β1 could also regulate S100A4 in endometrial cancer cells. TGF-β1 stimulated endometrial cancer cell migration and invasion with a concomitant increase in S100A4 protein. Induction of S100A4 was associated with the activation of Smads. TGF -β1 mediated endometrial cancer cell motility was inhibited by S100A4 siRNA. In aggregate, these results suggest that S100A4 is a critical mediator of invasion in endometrial cancer and is upregulated by the TGF-β1 signaling pathway. These results also suggest that endometrial cancer cell invasion and fibrosis share common molecular mechanisms. PMID:19506550

Endometrial thickness affects the outcome of in vitro fertilization and embryo transfer in normal responders after GnRH antagonist administration.

PubMed

Wu, Yu; Gao, Xiaohong; Lu, Xiang; Xi, Ji; Jiang, Shan; Sun, Yin; Xi, Xiaowei

2014-10-09

The goal of this study was to assess the association between endometrial thickness on the chorionic gonadotropin (hCG) day and in vitro fertilization and embryo transfer (IVF-ET) outcome in normal responders after GnRH antagonist administration. A retrospective cohort study was performed in normal responders with GnRH antagonist administration from January 2011-December 2013. Patients were divided into four groups according to endometrial thickness, as follows: <7 mm (group 1), > = 7- < 8 mm (group 2), > = 8- < 14 mm (group 3), and > =14 mm (group 4). A total of 2106 embryo transfer cycles were analyzed. The pregnancy rate (PR) was 44.87%.The clinical pregnancy rate, ongoing pregnancy rate and the implantation rate (17.28%, 13.79%, 10.17%, respectively) were significantly lower in group 1 compared to the other three groups (p < 0.05). The miscarriage rate was higher in patients with endometrial thickness less than 7 mm. The clinical pregnancy rate, ongoing pregnancy rate and implantation rate were highest in patients with endometrial thickness higher than 14 mm, but showed no difference in patients with those of endometrial thickness between 8-14 mm. There is a correlation between endometrial thickness measured on hCG day and clinical outcome in normal responders with GnRH antagonist administration. The pregnancy rate was lower in patients with endometrial thickness less than 7 mm compared with patients with endometrial thickness more than 7 mm.

Stromal deletion of the APC tumor suppressor in mice triggers development of endometrial cancer

PubMed Central

Tanwar, Pradeep S.; Zhang, LiHua; Roberts, Drucilla J.; Teixeira, Jose M.

2011-01-01

The contribution of the stromal microenvironment to the progression of endometrial cancer (EC) has not been well explored. We have conditionally expressed a mutant allele of adenomatous polyposis coli (APCcKO) in murine uterine stroma cells to study its effect on uterine development and function. In addition to metrorrhagia, the mice develop complex atypical endometrial gland hyperplasia that progresses to endometrial carcinoma in situ and endometrial adenocarcinoma as evidenced by myometrial invasion. Stromal cells subjacent to the carcinoma cells express αSMA with fewer cells expressing PDGFR-α compared to normal stromal cells suggesting that the mutant stromal cells have acquired a more myofibroblastic phenotype, which have been described as cancer-associated fibroblasts and have been shown to induce carcinogenesis in other organ systems. Analyses of human EC specimens showed substantial αSMA expression in the stroma compared with normal endometrial stroma cells. We also show that APCcKO mutant uteri and human EC have decreased stromal levels of TGFβ and BMP activities and that the mutant uteri failed to respond to exogenous estradiol stimulation. The mutant stroma cells also had higher levels of VEGF and SDF signaling components and diminished expression of ERα and PR which is common in advanced stages of human EC and is an indicator of poor prognosis. Our results indicate that de novo mutation or loss of heterozygosity in stromal APC is sufficient to induce endometrial hyperplasia and endometrial carcinogenesis by mechanisms that are consistent with unopposed estrogen signaling in the endometrial epithelium. PMID:21363919

Combination of Scoring Criteria and Whole Exome Sequencing Analysis of Synchronous Endometrial and Ovarian Carcinomas.

PubMed

Yang, Lingyi; Zhang, Lin; Huang, Qiujuan; Liu, Changxu; Qi, Lisha; Li, Lingmei; Qu, Tongyuan; Wang, Yalei; Liu, Suxiang; Meng, Bin; Sun, Baocun; Cao, Wenfeng

2018-05-01

The purpose of this study was to distinguish synchronous primary endometrial and ovarian carcinomas from single primary tumor with metastasis by clinical pathologic criteria and whole exome sequencing (WES). Fifty-two patients with synchronous endometrial and ovarian carcinomas (SEOCs) between 2010 and 2017 were reviewed and subjected to WES. On the basis of the Scully criteria, 11 cases were supposed as synchronous primary endometrial and ovarian carcinomas, 38 cases as single primary tumor with metastasis, and the remaining 3 cases (S50-S52) cannot be defined. Through a quantization scoring analysis, 9 cases that were scored 0-1 point were defined as synchronous primary endometrial and ovarian carcinomas, and 42 cases that were scored 3-8 points were defined as single primary tumor with metastasis. Two of the undefined cases were classified into metastatic disease, and another one that scored 2 points (S52) was subjected to WES. S52 was deemed synchronous primary endometrial and ovarian carcinomas, with few shared somatic mutations and overlapping copy number varieties. The finding of a serous component examined from the uterine endometrium samples further illustrated that the case was synchronous primary endometrial and ovarian carcinomas. By scoring criterion, SEOCs were divided into 2 groups: synchronous primary endometrial and ovarian carcinoma group and single primary tumor with metastasis group. The analysis of clonality indicated that the case that scored 2 (S52) can be considered as synchronous primary endometrial and ovarian carcinomas. Scoring criteria of clinical pathology, along with the study of the WES, may further identify the classification of SEOCs.

Biological Significance of Prolactin in Gynecological Cancers

PubMed Central

Levina, Vera V; Nolen, Brian; Su, YunYun; Godwin, Andrew K.; Fishman, David; Liu, Jinsong; Mor, Gil; Maxwell, Larry G.; Herberman, Ronald B.; Szczepanski, Miroslaw J.; Szajnik, Marta E.; Gorelik, Elieser; Lokshin, Anna E

2010-01-01

There is increasing evidence that Prolactin (PRL), a hormone/cytokine, plays a role in breast, prostate and colorectal cancers via local production or accumulation. Elevated levels of serum PRL in ovarian and endometrial cancers have been reported indicating a potential role for prolactin in endometrial and ovarian carcinogenesis. In this study, we demonstrate that serum PRL levels are significantly elevated in women with a strong family history of ovarian cancer. We demonstrate dramatically increased expression of PRL receptor (PRLR) in ovarian and endometrial tumors as well as in endometrial hyperplasia signifying the importance of PRL signaling in malignant and premalignant conditions. PRL mRNA was expressed in ovarian and endometrial tumors indicating the presence of an autocrine loop. PRL potently induced proliferation in several ovarian and endometrial cancer cell lines. Binding of PRL to its receptor was followed by rapid phosphorylation of ERK1/2, MEK-1, STAT3, CREB, ATF-2, and p53, and activation of 37 transcription factors in ovarian and endometrial carcinoma cells. PRL also activated Ras oncogene in these cells. When human immortalized normal ovarian epithelial (NOE) cells were chronically exposed to PRL a malignant transformation occurred manifested by the acquired ability of transformed cells to form clones, grow in soft agar, and form tumors in SCID-beige mice. Transformation efficiency was diminished by a Ras inhibitor providing proof that PRL-induced transformation utilizes the Ras pathway. In summary, we present findings that indicate an important role for PRL in ovarian and endometrial tumorigenesis. PRL may represent a risk factor for ovarian and endometrial cancers. PMID:19491263

Benign endometrial proliferations mimicking malignancies: a review of problematic entities in small biopsy specimens.

PubMed

Ip, Philip Pun-Ching

2018-02-14

Benign proliferations that mimic malignancies are commonly encountered during the course of assessment of small and fragmented endometrial samples. Although benign, endometrial epithelial metaplasias often coexist with premalignant or malignant lesions causing diagnostic confusion. The difficulty with mucinous metaplasia lies in its distinction from atypical mucinous glandular proliferations and mucinous carcinomas, which are associated with significant interobserver variability. Papillary proliferation of the endometrium is commonly associated with hormonal drugs and endometrial polyps and is characterised by papillae with fibrovascular cores covered by epithelial cells without cytologic atypia. They are classified into simple or complex papillary proliferations depending on the architectural complexity and extent of proliferation. Complex papillary proliferations are associated with a high risk of concurrent or subsequent hyperplasia with atypia/carcinoma. Papillary proliferations may have coexisting epithelial metaplasias and, most commonly, mucinous metaplasia and syncytial papillary change. Those with striking mucinous metaplasia overlap morphologically with papillary mucinous metaplasia. The latter has been proposed as a precursor of endometrial mucinous carcinoma. Misinterpreting the Arias-Stella reaction as a malignant or premalignant lesion is more likely to occur if the pathologist is unaware that the patient is pregnant or on hormonal drugs. Endometrial hyperplasia with secretory changes may occasionally be difficult to distinguish from the torturous and crowded glands of a late secretory endometrium. Endometrial polyps may have abnormal features that can be misinterpreted as endometrial hyperplasia or Mullerian adenosarcoma. Awareness of these benign endometrial proliferations and their common association with hormonal medication or altered endogenous hormonal levels will help prevent the over-diagnosis of premalignant and malignant lesions.

Medroxyprogesterone in Treating Patients With Endometrioid Adenocarcinoma of the Uterine Corpus

ClinicalTrials.gov

2016-03-17

Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Recurrent Uterine Corpus Carcinoma; Stage I Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage III Uterine Corpus Cancer; Stage IV Uterine Corpus Cancer

Comparison of serum androgens and endometrial thickness in obese and non-obese postmenopausal women

PubMed Central

Arıkan, İlker İnan; Barut, Aykut; Arıkan, Deniz; Harma, Müge; Harma, Mehmet İbrahim; Bozkurt, Serpil

2010-01-01

Objective In this study, we investigated whether serum androgen levels and endometrial thickness differed in obese and non-obese women. Material and Methods Thirtytwo non-obese (BMI <30) and 48 obese (BMI ≥ 30) women were enrolled. Blood samples were analyzed for testosterone, free testosterone, androstenedione, DHEAS, and SHBG, and transvaginal ultrasonography was performed. Results Obese women had significantly higher free testosterone and endometrial thickness and significantly lower SHBG. Eight of 17 women with endometrial thickness >5 mm had significant pathology. Conclusion These results suggest that obesity may be a risk factor for endometrial carcinoma and other pathologies in post-menopausal women through an action on androgen concentrations. PMID:24591922

Hormones and endometrial carcinogenesis.

PubMed

Kamal, Areege; Tempest, Nicola; Parkes, Christina; Alnafakh, Rafah; Makrydima, Sofia; Adishesh, Meera; Hapangama, Dharani K

2016-02-01

Endometrial cancer (EC) is the commonest gynaecological cancer in the Western World with an alarmingly increasing incidence related to longevity and obesity. Ovarian hormones regulate normal human endometrial cell proliferation, regeneration and function therefore are implicated in endometrial carcinogenesis directly or via influencing other hormones and metabolic pathways. Although the role of unopposed oestrogen in the pathogenesis of EC has received considerable attention, the emerging role of other hormones in this process, such as androgens and gonadotropin-releasing hormones (GnRH) is less well recognised. This review aims to consolidate the current knowledge of the involvement of the three main endogenous ovarian hormones (oestrogens, progesterone and androgens) as well as the other hormones in endometrial carcinogenesis, to identify important avenues for future research.

Emodin enhances the chemosensitivity of endometrial cancer by inhibiting ROS-mediated Cisplatin-resistance.

PubMed

Ding, Ning; Zhang, Hong; Su, Shan; Ding, Yumei; Yu, Xiaohui; Tang, Yujie; Wang, Qingfang; Liu, Peishu

2017-12-18

Background Endometrial cancer is a common cause of death in gynecological malignancies. Cisplatin is a clinically chemotherapeutic agent. However, drug-resistance is the primary cause of treatment failure. Objective Emodin is commonly used clinically to increase the sensitivity of chemotherapeutic agents, yet whether Emodin promotes the role of Cisplatin in the treatment of endometrial cancer has not been studied. Method CCK-8 kit was utilized to determine the growth of two endometrial cancer cell lines, Ishikawa and HEC-IB. The apoptosis level of Ishikawa and HEC-IB cells was detected by Annexin V / propidium iodide double-staining assay. ROS level was detected by DCFH-DA and NADPH oxidase expression. Expressions of drug-resistant genes were examined by real-time PCR and Western blotting. Results Emodin combined with Cisplatin reduced cell growth and increased the apoptosis of endometrial cancer cells. Co-treatment of Emodin and Cisplatin increased chemosensitivity by inhibiting the expression of drug-resistant genes through reducing the ROS levels in endometrial cancer cells. In an endometrial cancer xenograft murine model, the tumor size was reduced and animal survival time was increased by co-treatment of Emodin and Cisplatin. Conclusion This study demonstrates that Emodin enhances the chemosensitivity of Cisplatin on endometrial cancer by inhibiting ROS-mediated expression of drug-resistance genes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Ligand-Activated Peroxisome Proliferator-activated Receptor β/δ Modulates Human Endometrial Cancer Cell Survival

PubMed Central

MA, JJ; Monsivais, D; Dyson, MT; Coon, JS; Malpani, S; Ono, M; Zhao, H; Xin, H; Pavone, ME; Kim, JJ; Chakravarti, D; Bulun, SE

2013-01-01

Endometrial cancer is the fourth most common malignancy among women and is a major cause of morbidity- contributing to approximately 8,200 annual deaths in the United States. Despite advances to the understanding of endometrial cancer, novel interventions for the disease are necessary given that many tumors become refractory to therapy. As a strategy to identify novel therapies for endometrial carcinoma, in this study we examined the contribution of the peroxisome proliferator-activated receptor β/δ (PPARβ/δ) to endometrial cancer cell proliferation and apoptosis. We found that when activated with the highly selective PPARβ/δ agonists, GW0742 and GW501516, PPARβ/δ inhibited the proliferation and markedly induced the apoptosis of three endometrial cancer cell lines. The specificity of the PPARβ/δ-induced effects on cell proliferation and apoptosis was demonstrated using PPARβ/δ-selective antagonists and PPARβ/δ siRNA in combination with PPARβ/δ-selective agonists. Furthermore, we showed that PPARβ/δ activation increased PTEN expression, which led to AKT and GSK3β dephosphorylation, and increased β-catenin phosphorylation associated with its degradation. Overall, our data suggest that the anti-tumorigenic effect of PPARβ/δ activation in endometrial cancer is mediated through the negative regulation of the AKT/GSK3β/β-catenin pathway. These findings warrant further investigation of PPARβ/δ as a therapeutic target in endometrial cancer. PMID:23943160

Urokinase-type Plasminogen Activator Resulting from Endometrial Carcinogenesis Enhances Tumor Invasion and Correlates with Poor Outcome of Endometrial Carcinoma Patients

PubMed Central

Huang, Chia-Yen; Chang, Ming-Cheng; Huang, Wei-Yun; Huang, Ching-Ting; Tang, Yu-Chien; Huang, Hsien-Da; Kuo, Kuan-Ting; Chen, Chi-An; Cheng, Wen-Fang

2015-01-01

The purpose of this study was to identify the dysregulated genes involved in the tumorigenesis and progression of endometrial endometrioid adenocarcinoma (EEC), and their possible mechanisms. Endometrial specimens including normal endometrial tissues, atypical endometrial hyperplasia, and EEC were analyzed. The expression profiles were compared using GeneChip Array. The gene expression levels were determined by real-time RT-PCR in the training and testing sets to correlate the clinico-pathological parameters of EEC. Immunoblotting, in vitro cell migration and invasion assays were performed in human endometrial cancer cell lines and their transfectants. In microarray analysis, seven dysregulated genes were identified. Only the levels of urokinase-type plasminogen activator (uPA) were higher in EEC with deep myometrial invasion, positive lympho-vascular space invasion, lymph node metastasis, and advanced stages. After multivariate analysis, uPA was the only independent poor prognostic factor for disease-free survival in the EEC patients (hazard ratio: 4.65, p = 0.03). uPA may enhance the migratory and invasive capabilities of endometrial tumor cells by the phosphorylation of ERK1/2, Akt and p38 molecules. uPA is a dysregulated gene involved in the tumorigenesis, bio-pathological features and outcomes of EEC. uPA may be a potential molecule and target for the detection and treatment of EEC. PMID:26033187

Three-dimensional ultrasonography and power Doppler for discrimination between benign and malignant endometrium in premenopausal women with abnormal uterine bleeding.

PubMed

El-Sharkawy, Mohamed; El-Mazny, Akmal; Ramadan, Wafaa; Hatem, Dina; Abdel-Hafiz, Aly; Hammam, Mohamed; Nada, Adel

2016-03-16

Ultrasonography has been extensively used in women suspected of having a gynecological malignancy. The aim of this study is to evaluate the efficacy of 3D ultrasonography and power Doppler for discrimination between benign and malignant endometrium in premenopausal women with abnormal uterine bleeding. This cross-sectional study included 78 premenopausal women with abnormal uterine bleeding scheduled for hysteroscopy and endometrial curettage. The endometrial thickness (ET), uterine artery pulsatility index (PI) and resistance index (RI), and endometrial volume (EV) and 3D power Doppler vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured and compared with hysteroscopic and histopathologic findings. The ET (P <0.001), EV (P <0.001), and endometrial VI (P <0.001) and VFI (P = 0.043) were significantly increased in patients with atypical endometrial hyperplasia and endometrial carcinoma (n = 10) than those with benign endometrium (n = 68); whereas, the uterine artery PI and RI and endometrial FI were not significantly different between the two groups. The best marker for discrimination between benign and malignant endometrium was the VI with an area under the ROC curve of 0.88 at a cutoff value of 0.81%. 3D ultrasonography and power Doppler, especially endometrial VI, may be useful for discrimination between benign and malignant endometrium in premenopausal women with abnormal uterine bleeding.

Agreement of histopathological findings of uterine curettage and hysterectomy specimens in women with abnormal uterine bleeding.

PubMed

Moradan, Sanam; Ghorbani, Raheb; Lotfi, Azita

2017-05-01

To examined the diagnostic value of  dilatation and curettage (D and C) in patients with abnormal uterine bleeding (AUB) by conducting a histopathological examination of endometrial tissues by D and C and hysterectomy. Methods: In this retrospective study, the medical records of 163 women who had been hospitalized  in the Obstetrics and Gynecology Ward, Amir-al-Momenin Hospital, Semnan, Iran between 2010 and 2015 for diagnostic curettage due to  AUB and who had undergone hysterectomy were investigated. The patients' characteristics and histopathologic results of curettage and hysterectomy were extracted, and sensitivity and specificity and positive and negative predictive values of curettage were calculated. Results: The mean ± standard deviation age of the patients was 49.8±7.8 years. The sensitivity values of D and C in the diagnosis of endometrial pathologies was 49.1%, specificity 84.5%, positive 60.5%, and negative predictive 77.5%. The sensitivities of D and C in the diagnosis of various endometrial hyperplasia was 62.5%, disordered proliferative endometrium 36.8%, and endometrial cancer 83.3%. Of 6 patients with endometrial polyps on performing hysterectomy, no patient was diagnosed by curettage. Conclusions: Dilatation and curettage has acceptable sensitivity in the diagnosis of endometrial cancer, low sensitivity in the diagnosis of endometrial hyperplasia, and very low sensitivity in the diagnosis of disordered proliferative endometrium and endometrial polyps.

Agreement of histopathological findings of uterine curettage and hysterectomy specimens in women with abnormal uterine bleeding

PubMed Central

Moradan, Sanam; Ghorbani, Raheb; Lotfi, Azita

2017-01-01

Objectives: To examined the diagnostic value of dilatation and curettage (D&C) in patients with abnormal uterine bleeding (AUB) by conducting a histopathological examination of endometrial tissues by D&C and hysterectomy. Methods: In this retrospective study, the medical records of 163 women who had been hospitalized in the Obstetrics and Gynecology Ward, Amir-al-Momenin Hospital, Semnan, Iran between 2010 and 2015 for diagnostic curettage due to AUB and who had undergone hysterectomy were investigated. The patients’ characteristics and histopathologic results of curettage and hysterectomy were extracted, and sensitivity and specificity and positive and negative predictive values of curettage were calculated. Results: The mean ± standard deviation age of the patients was 49.8±7.8 years. The sensitivity values of D&C in the diagnosis of endometrial pathologies was 49.1%, specificity 84.5%, positive 60.5%, and negative predictive 77.5%. The sensitivities of D&C in the diagnosis of various endometrial hyperplasia was 62.5%, disordered proliferative endometrium 36.8%, and endometrial cancer 83.3%. Of 6 patients with endometrial polyps on performing hysterectomy, no patient was diagnosed by curettage. Conclusions: Dilatation and curettage has acceptable sensitivity in the diagnosis of endometrial cancer, low sensitivity in the diagnosis of endometrial hyperplasia, and very low sensitivity in the diagnosis of disordered proliferative endometrium and endometrial polyps. PMID:28439599

The Emerging Genomic Landscape of Endometrial Cancer

PubMed Central

Le Gallo, Matthieu; Bell, Daphne W.

2014-01-01

BACKGROUND Endometrial cancer is responsible for ~74,000 deaths amongst women worldwide each year. It is a heterogeneous disease that consists of multiple different histological subtypes. In the United States, the majority of deaths from endometrial carcinoma are attributed to the serous and endometrioid subtypes. An understanding of the fundamental genomic alterations that drive serous and endometrioid endometrial carcinomas lays the foundation for the identification of molecular markers that could improve the clinical management of patients presenting with these tumors. CONTENT Herein we review the current state of knowledge of the somatic genomic alterations that are present in serous and endometrioid endometrial tumors. We present this knowledge in a historical context – reviewing the genomic alterations that have been identified over the past two decades or more, from studies of individual genes and proteins, followed by a review of very recent studies that have conducted comprehensive, systematic surveys of genomic, exomic, transcriptomic, epigenomic, and proteomic alterations in serous and endometrioid endometrial carcinomas. SUMMARY The recent mapping of the genomic landscape of serous and endometrioid endometrial carcinomas has resulted in the first comprehensive molecular classification of these tumors and has distinguished four molecular subgroups: a POLE ultramutated subgroup, a hypermutated/microsatellite unstable subgroup, a copy number low/microsatellite stable subgroup, and a copy number high subgroup. This molecular classification may ultimately serve to refine the diagnosis and treatment of women with endometrioid and serous endometrial tumors. PMID:24170611

Obesity and Endometrial Cancer: A Lack of Knowledge but Opportunity for Intervention.

PubMed

Haggerty, Ashley F; Sarwer, David B; Schmitz, Kathryn H; Ko, Emily M; Allison, Kelly C; Chu, Christina S

2017-10-01

The causal link between obesity and endometrial cancer is well established; however obese women's knowledge of this relationship is unknown. Our objective was to explore patients' understanding of this relationship and assess the acceptability of a technology-based weight loss intervention. Obese women with Type I endometrial cancer/hyperplasia were surveyed about their assessment of their body mass, knowledge of the relationship of obesity and endometrial cancer, and eating and activity habits. Interest in participation in an intervention also was assessed. Eighty-one women with early stage (71.6% stage I) and grade (41.7% grade 1) disease completed the survey. The median BMI was 35.4 kg/m 2 (IQR 32.2-43.5 kg/m 2 ) and the average age was 59.3 (SD 11.1) yr. 76.25% of women were unable to categorize their BMI correctly and 86.9% of those incorrectly underestimated their BMI category. One-third (35.9%) were unaware of any association between obesity and endometrial cancer and 33.3% responded that obesity decreased or did not significantly increase the risk of endometrial cancer. 59% expressed interest in a weight loss intervention. Endometrial cancer survivors with obesity underestimated their obesity and lacked knowledge regarding the link between obesity and endometrial cancer. However, the majority expressed interest in electronically delivered weight loss interventions.

Relationship between uterine biopsy score, endometrial infection and inflammation in the mare.

PubMed

Buczkowska, Justyna; Kozdrowski, Roland; Nowak, Marcin; Sikora, Monika

2016-06-16

Endometrial biopsy score is an accepted marker of uterine health and predicted fertility, and it has been suggested that endometrial alternations are correlated with susceptibility to persistent infectious endometritis. The objective of this study was to investigate associations of endometrial biopsy score with: 1) presence of polymorphonuclear cells (PMNs) in the epithelium and stratum compactum in histopathology; 2) presence of PMNs in cytology and 3) presence of infection in microbiology. The material for examination was collected from 69 mares suspected for subclinical endometritis (bred three or more times unsuccessfully in the same breeding season) and from 15 maiden mares. Samples were collected by endometrial biopsy and cytobrush technique. Endometrial alterations (biopsy score IIA, IIB, III) were found in 64 of 82 mares (78%). There was an increase in PMN occurrence for grades IIA, IIB and III. When comparing grades and PMNs infiltration, we observed statistically significant differences between grades I and IIA (p  = 0.222) and grades I and IIB (p = 0.042) in samples collected by endometrial biopsy. Statistically significant differences were found in microbiological examination (biopsy p = 0.036; cytobrush p = 0.189), cytological examination (biopsy p = 0.040; cytobrush p = 0.079) and PMN infiltration (p    =    0.042) between mares with biopsy scores I and IIB. Furthermore, the highest percentage of infected mares was in grade IIA and IIB, and we found statistically significant differences between grades I and IIA (p = 0.043), and grades I and IIB (p = 0.036) in biopsy samples. We observed a tendency to higher prevalence of endometrial infection in mares with biopsy score IIA, IIB and III than with biopsy score I in samples collected using cytobrush technique. However, there were no statistical significant differences. Degenerative endometrial changes can predispose to uterine infection and inflammation. Our study shows that mares with endometrial score I are less predisposed to infection than mares with category IIA, IIB and III. Endometrial biopsy is a reliable diagnostic tool.

[Study of dynamic contrast-enhanced characteristics of stage-I endometrial carcinomas versus polyps with 3.0 T MRI].

PubMed

Wang, Xue; Lu, Yi; Zhang, Xiaoxia; Ji, Taotao; Liu, Kun; Ye, Xinjian; Bai, Guanghui; Yan, Zhihan

2015-01-20

To comparatively analyze the dynamic contrast-enhanced (DCE) characteristics and its clinical value between stage-I endometrial carcinomas versus polyps with 3.0T magnetic resonance imaging (MRI). A retrospective analysis was performed for DCE-MRI manifestation in 27 patients with histopathologically proved endometrial masses. There were stage-I endometrial carcinomas (n = 14) and polyps (n = 13). The signal intensity of solid component was measured and time-intensity curves (TIC) was obtained. TIC of lesions were divided into 4 subtypes. The time-to-peak (TTP) and signal intensity (SI) were determined from TICs. The arterial phase relative signal increase ratio (ARSIR), maximal relative signal increase ratio (MRSIR), signal enhancement ratio (SER) and signal intensity difference values (D) of each phase were calculated based on TIC curves respectively. The TIC of 14 stage-I endometrial carcinomas included type I (n = 4), type II (n = 6) and type IV (n = 4). The TIC of 13 polyps included type III (n = 3) and type IV (n = 10). The D values in each phase of 14 stage-I endometrial carcinomas were lower than normal muscle layers. There were statistic differences (P < 0.05) of each phase including 32, 48, 64, 109, 154, 199 s. For stage-I endometrial carcinomas, MRSIR and TTP were lower (P < 0.01) than normal muscle layers while SER was higher (P < 0.01) than normal muscle layers . The each phase of D of stage-I endometrial carcinomas were lower than polyps, and there were statistic differences (P < 0.05) of each phase including 32, 48, 64, 109, 154, 199 s. The MRSIR and TTP of stage-I endometrial carcinomas were lower (P < 0.01) than those of polyps while SER was higher (P < 0.01) than polyps. DCE-MRI can reflect enhanced features of stage-I endometrial carcinomas and polyps during different phases quantitatively. Parameters of DCE-MR and TIC are helpful in the diagnosis and differential diagnosis of stage-I endometrial carcinomas versus polyps.

Adjuvant Brachytherapy Removes Survival Disadvantage of Local Disease Extension in Stage IIIC Endometrial Cancer: A SEER Registry Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rossi, Peter J.; Jani, Ashesh B.; Horowitz, Ira R.

2008-01-01

Purpose: To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. Methods and Materials: The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ-confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were comparedmore » using the log-rank test. Results: The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p <0.001). In patients with organ-confined Stage IIIC endometrial cancer, the 5-year OS rate was 50% for NAT, 64% for EBRT, and 67% for EBRT/BT. Again, adjuvant RT contributed to improved survival compared with NAT (p = 0.02). In patients with Stage IIIC endometrial cancer and direct tumor extension, the 5-year OS rate was 34% for NAT, 47% for EBRT, and 63% for EBRT/BT. RT improved OS compared with NAT (p <0.001). Also, in this high-risk subgroup, adding BT to EBRT was superior to EBRT alone (p = 0.002). Conclusion: Women with Stage IIIC endometrial cancer receiving adjuvant EBRT and EBRT/BT had improved OS compared with patients receiving NAT. When direct extension of the primary tumor was present, the addition of BT to EBRT was even more beneficial.« less

Adjuvant brachytherapy removes survival disadvantage of local disease extension in stage IIIC endometrial cancer: a SEER registry analysis.

PubMed

Rossi, Peter J; Jani, Ashesh B; Horowitz, Ira R; Johnstone, Peter A S

2008-01-01

To assess the role of radiotherapy (RT) in women with Stage IIIC endometrial cancer. The 17-registry Survival, Epidemiology, and End Results (SEER) database was searched for patients with lymph node-positive non-Stage IV epithelial endometrial cancer diagnosed and treated between 1988 and 1998. Two subgroups were identified: those with organ-confined Stage IIIC endometrial cancer and those with Stage IIIC endometrial cancer with direct extension of the primary tumor. RT was coded as external beam RT (EBRT) or brachytherapy (BT). Observed survival (OS) was reported with a minimum of 5 years of follow-up; the survival curves were compared using the log-rank test. The therapy data revealed 611 women with Stage IIIC endometrial cancer during this period. Of these women, 51% were treated with adjuvant EBRT, 21% with EBRT and BT, and 28% with no additional RT (NAT). Of the 611 patients, 293 had organ-confined Stage IIIC endometrial cancer and 318 patients had Stage IIIC endometrial cancer with direct extension of the primary tumor. The 5-year OS rate for all patients was 40% with NAT, 56% after EBRT, and 64% after EBRT/BT. Adjuvant RT improved survival compared with NAT (p <0.001). In patients with organ-confined Stage IIIC endometrial cancer, the 5-year OS rate was 50% for NAT, 64% for EBRT, and 67% for EBRT/BT. Again, adjuvant RT contributed to improved survival compared with NAT (p = 0.02). In patients with Stage IIIC endometrial cancer and direct tumor extension, the 5-year OS rate was 34% for NAT, 47% for EBRT, and 63% for EBRT/BT. RT improved OS compared with NAT (p <0.001). Also, in this high-risk subgroup, adding BT to EBRT was superior to EBRT alone (p = 0.002). Women with Stage IIIC endometrial cancer receiving adjuvant EBRT and EBRT/BT had improved OS compared with patients receiving NAT. When direct extension of the primary tumor was present, the addition of BT to EBRT was even more beneficial.

Levonorgestrel intrauterine system for endometrial protection in women with breast cancer on adjuvant tamoxifen.

PubMed

Dominick, Sally; Hickey, Martha; Chin, Jason; Su, H Irene

2015-12-09

Adjuvant tamoxifen reduces the risk of breast cancer recurrence in women with oestrogen receptor-positive breast cancer. Tamoxifen also increases the risk of postmenopausal bleeding, endometrial polyps, hyperplasia, and endometrial cancer. The levonorgestrel-releasing intrauterine system (LNG-IUS) causes profound endometrial suppression. This systematic review considered the evidence that the LNG-IUS prevents the development of endometrial pathology in women taking tamoxifen as adjuvant endocrine therapy for breast cancer. To determine the effectiveness and safety of levonorgestrel intrauterine system (LNG-IUS) in pre- and postmenopausal women taking adjuvant tamoxifen following breast cancer for the outcomes of endometrial and uterine pathology including abnormal vaginal bleeding or spotting, and secondary breast cancer events. We searched the following databases: Cochrane Menstrual Disorders and Subfertility Group Specialised Register (MDSG), Cochrane Breast Cancer Group Specialised Register (CBCG), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Abstracts of Reviews of Effects (DARE), The Cochrane Library, clinicaltrials.gov, The World Health Organisation International Trials Registry, ProQuest Dissertations & Theses, MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, Web of Science, OpenGrey, LILACS, PubMed, and Google. The final search was performed in October 2015. Randomised controlled trials of women with breast cancer on adjuvant tamoxifen that compared endometrial surveillance alone (control condition) versus the LNG-IUS with endometrial surveillance (experimental condition) on the incidence of endometrial pathology. Study selection, risk of bias assessment and data extraction were performed independently by two review authors. The primary outcome measure was endometrial pathology (including polyps, endometrial hyperplasia, or endometrial cancer) diagnosed at hysteroscopy or endometrial biopsy. Secondary outcome measures included fibroids, abnormal vaginal bleeding or spotting, breast cancer recurrence, and breast cancer-related deaths. The overall quality of evidence was rated using GRADE methods. Four randomised controlled trials involving 543 women were identified and are included in this review. In the included studies, the active treatment arm was the 20 μg/day levonorgestrel-releasing intrauterine system (LNG-IUS) plus endometrial surveillance; the control arm was endometrial surveillance alone. In tamoxifen users, the LNG-IUS led to a reduction in the incidence of endometrial polyps over both a 12-month period (Peto OR 0.22, 95% CI 0.08 to 0.64, 2 studies, n = 212, I² = 0%) and over a long-term follow-up period (24 to 60 months) (Peto OR 0.22, 95% CI 0.13 to 0.39, 4 studies, n = 417, I² = 0%, moderate quality evidence). Also the LNG-IUS led to a reduction in the incidence of endometrial hyperplasia over a long-term follow-up period (24 to 60 months) (Peto OR 0.13, 95% CI 0.03 to 0.67, four studies, n = 417, I² = 0%, moderate quality evidence). However, it should be noted that the number of events of endometrial hyperplasia was low (n = 6). None of the trials were sufficiently powered to detect whether LNG-IUS leads to significant changes in the incidence of endometrial cancer in tamoxifen users. At 12 months of follow-up abnormal vaginal bleeding or spotting was more common in the LNG-IUS treatment group (Peto OR 7.26, 95% CI 3.37 to 15.66, 3 studies, n = 376, I² = 0%, moderate quality evidence). By 24 months of follow-up, abnormal vaginal bleeding or spotting occurred less frequently compared to 12 months of follow-up in the LNG-IUS treatment group but was still more common than the control group (Peto OR 2.72, 95% CI 1.04 to 7.10, 2 studies, n = 233, I² = 0%, moderate quality evidence). By 60 months of follow-up, no cases of abnormal vaginal bleeding or spotting were reported in either group. The numbers of events for the following outcomes were low: fibroids (n = 13), breast cancer recurrence (n = 18), and breast cancer-related deaths (n = 16). There was no evidence of a difference between the LNG-IUS treatment group and controls for these outcomes. The quality of the evidence was judged as moderate, due to limited sample sizes and low event rates for the outcome comparisons. The LNG-IUS reduces the incidence of benign endometrial polyps and endometrial hyperplasia in women with breast cancer taking tamoxifen. At 12 and 24 months of follow-up, the LNG-IUS increased abnormal vaginal bleeding or spotting among women in the treatment group compared to those in the control. There is no clear evidence from the available randomised controlled trials that the LNG-IUS prevents endometrial cancer in these women. There is no clear evidence from the available randomised controlled trials that the LNG-IUS affects the risk of breast cancer recurrence or breast cancer-related deaths. Larger studies are necessary to assess the effects of the LNG-IUS on the incidence of endometrial cancer, and to determine whether the LNG-IUS might have an impact on the risk of secondary breast cancer events.

Endometrial Cancer Screening (PDQ®)—Patient Version

Cancer.gov

Endometrial cancer screening is currently not recommended because no standard or routine screening test has been shown to be effective. Endometrial cancer is usually found early due to symptoms and survival rates are high. Learn more in this expert-reviewed summary.

Endometrial Cancer Screening

MedlinePlus

... decrease the risk of dying from cancer. Scientists study screening tests to find those with the fewest risks and ... recovery. There is no standard or routine screening test for endometrial cancer. Screening for endometrial cancer is under study and there are screening clinical trials taking place ...

Long-chain ω-3 fatty acid intake and endometrial cancer risk in the Women’s Health Initiative12345

PubMed Central

Brasky, Theodore M; Rodabough, Rebecca J; Liu, Jingmin; Kurta, Michelle L; Wise, Lauren A; Orchard, Tonya S; Cohn, David E; Belury, Martha A; White, Emily; Manson, JoAnn E; Neuhouser, Marian L

2015-01-01

Background: Inflammation may be important in endometrial cancer development. Long-chain ω-3 (n–3) polyunsaturated fatty acids (LCω-3PUFAs) may reduce inflammation and, therefore, reduce cancer risk. Because body mass is associated with both inflammation and endometrial cancer risk, it may modify the association of fat intake on risk. Objective: We examined whether intakes of LCω-3PUFAs were associated with endometrial cancer risk overall and stratified by body size and histologic subtype. Design: Women were n = 87,360 participants of the Women’s Health Initiative Observational Study and Clinical Trials who were aged 50–79 y, had an intact uterus, and completed a baseline food-frequency questionnaire. After 13 y of follow-up, n = 1253 incident invasive endometrial cancers were identified. Cox regression models were used to estimate HRs and 95% CIs for the association of intakes of individual ω-3 fatty acids and fish with endometrial cancer risk. Results: Intakes of individual LCω-3PUFAs were associated with 15–23% linear reductions in endometrial cancer risk. In women with body mass index (BMI; in kg/m2) <25, those in the upper compared with lowest quintiles of total LCω-3PUFA intake (sum of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) had significantly reduced endometrial cancer risk (HR: 0.59; 95% CI: 0.40, 0.82; P-trend = 0.001), whereas there was little evidence of an association in overweight or obese women. The reduction in risk observed in normal-weight women was further specific to type I cancers. Conclusions: Long-chain ω-3 intake was associated with reduced endometrial cancer risk only in normal-weight women. Additional studies that use biomarkers of ω-3 intake are needed to more accurately estimate their effects on endometrial cancer risk. This trial was registered at clinicaltrials.gov as NCT00000611. PMID:25739930

Does experience in hysteroscopy improve accuracy and inter-observer agreement in the management of abnormal uterine bleeding?

PubMed

Bourdel, Nicolas; Modaffari, Paola; Tognazza, Enrica; Pertile, Riccardo; Chauvet, Pauline; Botchorishivili, Revaz; Savary, Dennis; Pouly, Jean Luc; Rabischong, Benoit; Canis, Michel

2016-12-01

Hysteroscopic reliability may be influenced by the experience of the operator and by a lack of morphological diagnostic criteria for endometrial malignant pathologies. The aim of this study was to evaluate the diagnostic accuracy and the inter-observer agreement (IOA) in the management of abnormal uterine bleeding (AUB) among different experienced gynecologists. Each gynecologist, without any other clinical information, was asked to evaluate the anonymous video recordings of 51 consecutive patients who underwent hysteroscopy and endometrial resection for AUB. Experts (>500 hysteroscopies), seniors (20-499 procedures) and junior (≤19 procedures) gynecologists were asked to judge endometrial macroscopic appearance (benign, suspicious or frankly malignant). They also had to propose the histological diagnosis (atrophic or proliferative endometrium; simple, glandulocystic or atypical endometrial hyperplasia and endometrial carcinoma). Observers were free to indicate whether the quality of recordings were not good enough for adequate assessment. IOA (k coefficient), sensitivity, specificity, predictive value and the likelihood ratio were calculated. Five expert, five senior and six junior gynecologists were involved in the study. Considering endometrial cancer and endometrial atypical hyperplasia, sensitivity and specificity were respectively 55.5 % and 84.5 % for juniors, 66.6 % and 81.2 % for seniors and 86.6 % and 87.3 % for experts. Concerning endometrial macroscopic appearance, IOA was poor for juniors (k = 0.10) and fair for seniors and experts (k = 0.23 and 0.22, respectively). IOA was poor for juniors and experts (k = 0.18 and 0.20, respectively) and fair for seniors (k = 0.30) in predicting the histological diagnosis. Sensitivity improves with the observer's experience, but inter-observer agreement and reproducibility of hysteroscopy for endometrial malignancies are not satisfying no matter the level of expertise. Therefore, an accurate and complete endometrial sampling is still needed.

Polymorphisms in inflammation pathway genes and endometrial cancer risk

PubMed Central

Delahanty, Ryan J.; Xiang, Yong-Bing; Spurdle, Amanda; Beeghly-Fadiel, Alicia; Long, Jirong; Thompson, Deborah; Tomlinson, Ian; Yu, Herbert; Lambrechts, Diether; Dörk, Thilo; Goodman, Marc T.; Zheng, Ying; Salvesen, Helga B.; Bao, Ping-Ping; Amant, Frederic; Beckmann, Matthias W.; Coenegrachts, Lieve; Coosemans, An; Dubrowinskaja, Natalia; Dunning, Alison; Runnebaum, Ingo B.; Easton, Douglas; Ekici, Arif B.; Fasching, Peter A.; Halle, Mari K.; Hein, Alexander; Howarth, Kimberly; Gorman, Maggie; Kaydarova, Dylyara; Krakstad, Camilla; Lose, Felicity; Lu, Lingeng; Lurie, Galina; O’Mara, Tracy; Matsuno, Rayna K.; Pharoah, Paul; Risch, Harvey; Corssen, Madeleine; Trovik, Jone; Turmanov, Nurzhan; Wen, Wanqing; Lu, Wei; Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou

2013-01-01

Background Experimental and epidemiological evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. Methods To investigate this hypothesis, a two-stage study was carried out to evaluate single nucleotide polymorphisms (SNPs) in inflammatory pathway genes in association with endometrial cancer risk. In stage 1, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage 1 SNPs significantly associated with endometrial cancer (P<0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage 2, which consisted of ten additional studies including 6,604 endometrial cancer cases and 8,511 controls. Results Five of the 21 SNPs had significant allelic odds ratios and 95% confidence intervals as follows: FABP1, 0.92 (0.85-0.99); CXCL3, 1.16 (1.05-1.29); IL6, 1.08 (1.00-1.17); MSR1, 0.90 (0.82-0.98); and MMP9, 0.91 (0.87-0.97). Two of these polymorphisms were independently significant in the replication sample (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry samples. Conclusions These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact Statement This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis. PMID:23221126

CHEK2, MGMT, SULT1E1 and SULT1A1 polymorphisms and endometrial cancer risk.

PubMed

O'Mara, Tracy A; Ferguson, Kaltin; Fahey, Paul; Marquart, Louise; Yang, Hannah P; Lissowska, Jolanta; Chanock, Stephen; Garcia-Closas, Montserrat; Thompson, Deborah J; Healey, Catherine S; Dunning, Alison M; Easton, Douglas F; Webb, Penelope M; Spurdle, Amanda B

2011-08-01

Several single nucleotide polymorphisms (SNPs) in candidate genes of DNA repair and hormone pathways have been reported to be associated with endometrial cancer risk. We sought to confirm these associations in two endometrial cancer case-control sample sets and used additional data from an existing genome-wide association study to prioritize an additional SNP for further study. Five SNPs from the CHEK2, MGMT, SULT1E1 and SULT1A1 genes, genotyped in a total of 1597 cases and 1507 controls from two case-control studies, the Australian National Endometrial Cancer Study and the Polish Endometrial Cancer Study, were assessed for association with endometrial cancer risk using logistic regression analysis. Imputed data was drawn for CHEK2 rs8135424 for 666 cases from the Study of Epidemiology and Risk factors in Cancer Heredity study and 5190 controls from the Wellcome Trust Case Control Consortium. We observed no association between SNPs in the MGMT, SULT1E1 and SULT1A1 genes and endometrial cancer risk. The A allele of the rs8135424 CHEK2 SNP was associated with decreased risk of endometrial cancer (adjusted per-allele OR 0.83; 95%CI 0.70-0.98; p = .03) however this finding was opposite to that previously published. Imputed data for CHEK2 rs8135424 supported the direction of effect reported in this study (OR 0.85; 95% CI 0.65-1.10). Previously reported endometrial cancer risk associations with SNPs from in genes involved in estrogen metabolism and DNA repair were not replicated in our larger study population. This study highlights the need for replication of candidate gene SNP studies using large sample groups, to confirm risk associations and better prioritize downstream studies to assess the causal relationship between genetic variants and cancer risk. Our findings suggest that the CHEK2 SNP rs8135424 be prioritized for further study as a genetic factor associated with risk of endometrial cancer.

Ovarian and endometrial endometrioid carcinomas have distinct CTNNB1 and PTEN mutation profiles.

PubMed

McConechy, Melissa K; Ding, Jiarui; Senz, Janine; Yang, Winnie; Melnyk, Nataliya; Tone, Alicia A; Prentice, Leah M; Wiegand, Kimberly C; McAlpine, Jessica N; Shah, Sohrab P; Lee, Cheng-Han; Goodfellow, Paul J; Gilks, C Blake; Huntsman, David G

2014-01-01

Ovarian endometrioid carcinomas and endometrial endometrioid carcinomas share many histological and molecular alterations. These similarities are likely due to a common endometrial epithelial precursor cell of origin, with most ovarian endometrioid carcinomas arising from endometriosis. To directly compare the mutation profiles of two morphologically similar tumor types, endometrial endometrioid carcinomas (n=307) and ovarian endometrioid carcinomas (n=33), we performed select exon capture sequencing on a panel of genes: ARID1A, PTEN, PIK3CA, KRAS, CTNNB1, PPP2R1A, TP53. We found that PTEN mutations are more frequent in low-grade endometrial endometrioid carcinomas (67%) compared with low-grade ovarian endometrioid carcinomas (17%) (P<0.0001). By contrast, CTNNB1 mutations are significantly different in low-grade ovarian endometrioid carcinomas (53%) compared with low-grade endometrial endometrioid carcinomas (28%) (P<0.0057). This difference in CTNNB1 mutation frequency may be reflective of the distinct microenvironments; the epithelial cells lining an endometriotic cyst within the ovary are exposed to a highly oxidative environment that promotes tumorigenesis. Understanding the distinct mutation patterns found in the PI3K and Wnt pathways of ovarian and endometrial endometrioid carcinomas may provide future opportunities for stratifying patients for targeted therapeutics.

Overexpression and oncogenic function of HMGA2 in endometrial serous carcinogenesis

PubMed Central

Wei, Linxuan; Liu, Xiaolin; Zhang, Wenjing; Wei, Yuyan; Li, Yingwei; Zhang, Qing; Dong, Ruifen; Kwon, Jungeun Sarah; Liu, Zhaojian; Zheng, Wenxin; Kong, Beihua

2016-01-01

The high-mobility group A protein 2 (HMGA2) is a non-histone chromatin factor highly expressed in fetal tissue and malignant tumors but rarely detected within normal adult tissues. The clinical implications and biological functions of HMGA2 in endometrial carcinoma are largely unknown. Here we report that HMGA2 expression was barely detected in benign endometrium samples (2 of 28 samples). However, HMGA2 expression increased significantly from precancerous lesion endometrial glandular dysplasia (7 of 17, 41.2%), to serous endometrial intraepithelial carcinoma (5 of 8, 62.5%) and to full blown endometrial serous carcinoma (39 of 59, 66.1%). Functional characterization of HMGA2 revealed that the gene has both tumor growth promotion and metastasis. In addition, HMGA2 induced epithelial-mesenchymal transition (EMT) through modulation vimentin and β-catenin. Furthermore, HMGA2 overexpression started from endometrial serous precancers, non-invasive cancers, as well as in full blown carcinomas in a p53 knockout mouse model we recently established in our laboratory. Our findings suggest that HMGA2 may serve as a useful diagnostic marker in the assessment of endometrial serous cancer and its precursor lesions. PMID:27186400

Risks of Endometrial Cancer Screening

MedlinePlus

... decrease the risk of dying from cancer. Scientists study screening tests to find those with the fewest risks and ... recovery. There is no standard or routine screening test for endometrial cancer. Screening for endometrial cancer is under study and there are screening clinical trials taking place ...

Malignant mixed Mullerian tumour of uterus secondary to tamoxifen therapy for hormone responsive breast cancer.

PubMed

Gupta, Mayank; Kiruthiga, Kala Gnanasekaran

2015-06-29

Tamoxifen is used in the treatment of hormone responsive breast cancer because of its antiestrogenic effect. However, it also has an estrogenic effect on the uterus, thereby increasing the risk of endometrial hyperplasia, endometrial polyp and endometrial neoplasms such as endometrial adenocarcinoma and malignant mixed Mullerian tumour (MMMT). This case describes the possible pathogenesis and risk of developing MMMT due to long-term tamoxifen intake in hormone responsive breast cancer. 2015 BMJ Publishing Group Ltd.

A critical assessment on the role of sentinel node mapping in endometrial cancer.

PubMed

Bogani, Giorgio; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Perotto, Stefania; Lorusso, Domenica; Raspagliesi, Francesco

2015-10-01

Endometrial cancer is the most common gynecologic malignancy in the developed countries. Although the high incidence of this occurrence no consensus, about the role of retroperitoneal staging, still exists. Growing evidence support the safety and efficacy of sentinel lymph node mapping. This technique is emerging as a new standard for endometrial cancer staging procedures. In the present paper, we discuss the role of sentinel lymph node mapping in endometrial cancer, highlighting the most controversies features.

Controversies in the Management of Endometrial Carcinoma: An Update

PubMed Central

Mehasseb, Mohamed K.; Latimer, John A.

2012-01-01

Endometrial carcinoma is the commonest type of female genital tract malignancy in the developed countries. Endometrial carcinoma is usually confined to the uterus at the time of diagnosis and as such usually carries an excellent prognosis with high curability. Our understanding and management of endometrial cancer have continuously developed. Current controversies focus on screening and early detection, the extent of nodal surgery, and the changing roles of radiation therapy and chemotherapy and will be discussed in this paper. PMID:22518164

[Expression of SLP-2 mRNA in endometrial cancer and its significance].

PubMed

Feng, Wang-qin; Cui, Zhu-mei; Feng, Feng-zhi; Qi, Xiu-juan; Ding, Fang; Li, Wen-dong; Liu, Zhi-hua

2005-08-01

To characterize the differential expression of SLP-2 in endometrial cancer, and to study the effect of human SLP-2 gene on human endometrial cancer cell line. The expression of SLP-2 gene in 32 cases of endometrial cancer and 28 cases of normal endometrial tissues was examined by semi-quantitative RT-PCR. Eukaryotic expression vectors of sense and antisense SLP-2 were constructed and transfected into HEC-1B cell line using lipofectamine 2000 respectively. The morphological changes of the cell were observed by phase contrast microscopy. The cell growth was detected by methyl thiazolyl tetrazolium (MTT) assay, and the cell cycles were analyzed by flow cytometry. The expression of SLP-2 mRNA in endometrial cancer tissues was higher than that in normal endometrial tissues (1.6 +/- 0.7 vs 0.7 +/- 0.3, P < 0.05). Sense and antisense human SLP-2 constructs were transfected into HEC-1B cell line respectively. After being transfected with sense SLP-2, the expression of SLP-2 mRNA in HEC-1B cell line was increased by about 2.4 times that of the control group, the cell growth was accelerated, and the number of cells in G(1) phase was decreased by 12.5%, S phase was increased by 8.0%. After being transfected with antisense SLP-2, the expression of SLP-2 mRNA was declined 50%. The transfected cells showed slower growth, and the number of cells in G(1) phase was significantly increased by 10.5%, and S phase was declined by 9.8%. SLP-2 mRNA shows up-regulation in endometrial cancer tissues, and it may have some relationship with carcinogenesis of endometrial cancer.

A Prospective Cohort Study of Coffee Consumption and Risk of Endometrial Cancer over a 26-year of Follow-Up

PubMed Central

Je, Youjin; Hankinson, Susan E.; Tworoger, Shelley S.; DeVivo, Immaculata; Giovannucci, Edward

2011-01-01

Background Coffee has been reported to lower levels of estrogen and insulin, two hormones implicated in endometrial carcinogenesis, but prospective data on the relation between coffee consumption and risk of endometrial cancer are limited. Methods We prospectively assessed coffee consumption in relation to endometrial cancer risk in the Nurses’ Health Study (NHS) with 67,470 female participants aged 34–59 in 1980. Cumulative average coffee intake was calculated with all available questionnaires to assess long-term effects. Cox regression models were used to calculate incidence rate ratios (RR), controlling for other risk factors. Results Fewer than 4 cups of coffee per day were not associated with endometrial cancer risk. However, women who consumed 4 or more cups of coffee had 25% lower risk of endometrial cancer than those who consumed less than 1 cup per day (multivariable RR=0.75; 95% CI =0.57–0.97; Ptrend = 0.02). We found the similar association with caffeinated coffee consumption (RR for ≥ 4 vs. <1 cup/day = 0.70; 95% CI = 0.51–0.95). For decaffeinated coffee consumption, a suggestive inverse association was found among women who consumed 2 or more cups per day vs. <1 cup/month. Tea consumption was not associated with endometrial cancer risk. Conclusions These prospective data suggest that 4 or more cups of coffee per day are associated with a lower risk of endometrial cancer. Impact Drinking of coffee, given its widespread consumption, might be an additional strategy to reduce endometrial cancer risk. However, addition of substantial sugar and cream to coffee could offset any potential benefits. PMID:22109346

Long-term Cardiovascular Outcomes Among Endometrial Cancer Survivors in a Large, Population-Based Cohort Study.

PubMed

Soisson, Sean; Ganz, Patricia A; Gaffney, David; Rowe, Kerry; Snyder, John; Wan, Yuan; Deshmukh, Vikrant; Newman, Mike; Fraser, Alison; Smith, Ken; Herget, Kimberly; Hanson, Heidi A; Wu, Yelena P; Stanford, Joseph; Al-Sarray, Ali; Werner, Theresa L; Setiawan, Veronica W; Hashibe, Mia

2018-05-08

Endometrial cancer is the second most common cancer among female cancer survivors in the United States. Cardiovascular disease is the leading cause of death among endometrial cancer survivors. Studies that examine long-term cardiovascular outcomes among endometrial cancer survivors are critical. Cohorts of 2648 endometrial cancer survivors diagnosed between 1997 and 2012 and 10 503 age-matched women from the general population were identified. Cardiovascular disease diagnoses were identified from electronic medical records and statewide ambulatory surgery and statewide inpatient data. Cox regression models were used to estimate hazard ratios (HRs) at one to five years, more than five to 10 years, and more than 10 years after cancer diagnosis. Between one and five years after diagnosis, increased cardiovascular risks among endometrial cancer survivors were observed for phlebitis, thrombophlebitis, and thromboembolism (HR = 2.07, 99% confidence interval [CI] = 1.57 to 2.72), pulmonary heart disease (HR = 1.74, 99% CI = 1.26 to 2.40), and atrial fibrillation (HR = 1.50, 99% CI = 1.07 to 2.11). At more than five to 10 years, some elevated risk persisted for cardiovascular diseases. Compared with patients who had surgery, patients who additionally had radiation therapy and/or chemotherapy were at increased risk for heart and circulatory system disorders between one and five years after cancer diagnosis. Older age and obesity were also risk factors for hypertension and heart disease among endometrial cancer survivors. Endometrial cancer survivors are at higher risk for various adverse long-term cardiovascular outcomes compared with women from the general population. This study suggests that increased monitoring for cardiovascular diseases may be necessary for endometrial cancer patients for 10 years after cancer diagnosis.

Inhibin/activin-betaC and -betaE subunits in the Ishikawa human endometrial adenocarcinoma cell line.

PubMed

Kimmich, Tanja; Brüning, Ansgar; Käufl, Stephanie D; Makovitzky, Josef; Kuhn, Christina; Jeschke, Udo; Friese, Klaus; Mylonas, Ioannis

2010-08-01

Inhibins and activins are important regulators of the female reproductive system. Recently, two novel inhibin subunits, named betaC and betaE, have been identified and shown to be expressed in several human tissues. However, only limited data on the expression of these novel inhibin subunits in normal human endometrial tissue and endometrial adenocarcinoma cell lines exist. Samples of proliferative and secretory human endometrium were obtained from five premenopausal, non-pregnant patients undergoing gynecological surgery for benign diseases. Normal endometrial tissue and Ishikawa endometrial adenocarcinoma cell lines were analyzed by immunohistochemistry, immunofluorescence and RT-PCR. Expression of the inhibin betaC and betaE subunits could be demonstrated at the protein level by means of immunohistochemical evaluation and at the transcriptional level by establishing a betaC- and betaE-specific RT-PCR analysis in normal human endometrial tissue and the parental Ishikawa cell line. Interestingly, in a highly de-differentiated subclone of the Ishikawa cell line lacking estrogen receptor expression, the expression of the inhibin-betaC subunit appeared strongly reduced. Here, we show for the first time that the novel inhibin/activin-betaC and -betaE subunits are expressed in normal human endometrium and the estrogen receptor positive human endometrial carcinoma cell line Ishikawa using RT-PCR and immunohistochemical detection methods. Interestingly, the Ishikawa minus cell line (lacking estrogen receptor expression) demonstrated no to minimal expression of the betaC subunit as observed with immunofluorescence and RT-PCR, suggesting a possible hormone- dependency of this subunit in human endometrial cancer cells. Moreover, because the Ishikawa cell line minus is thought to be a more malignant endometrial cell line than its estrogen receptor positive counterpart, inhibin-betaC subunit might be substantially involved in the pathogenesis and malignant transformation in human endometrium.

The prevalence of occult endometrial cancer in women undergoing hysterectomy for benign indications.

PubMed

Parsons, Lavanya H Palavalli; Pedersen, Rebecca; Richardson, Debra L; Kho, Kimberly A

2018-04-01

To estimate the frequency of occult endometrial cancer in women undergoing hysterectomy for benign indications. We performed a retrospective review of all patients undergoing hysterectomies for benign indications at our institution from 2006 to 2014. A departmental database was used to identify all hysterectomies performed, and institutional tumor registry was used to identify cases of endometrial carcinoma. Occult carcinomas were defined as cases with no suspicion preoperatively and histopathologic diagnosis of endometrial cancer postoperatively. A total of 6981 hysterectomies were performed for benign indications. Among these, thirteen patients (0.19%) were found to have occult endometrial cancer, with an overall rate of 1 in 537 patients (95% confidence interval 1:314-1:1008). Twelve patients had stage IA and one had stage IB disease. Median age of women found to have endometrial cancer was 50 years (range 35-72 years). The median BMI was 29.8 kg/m 2 (range 21.3-50.4 kg/m 2 ). The most common indications for hysterectomy were abnormal bleeding (47%), postmenopausal bleeding (15%), adnexal mass (15%), prolapse (15%), and endometrial hyperplasia without atypia (8%). Of the postmenopausal women that had bleeding, all patients underwent evaluation of the endometrium, however 75% of samples did not have adequate amount of endometrium to be evaluated and 25% were found to have hyperplasia. This is one of the largest single institution cohorts to examine occult malignancy. Unexpected endometrial carcinomas were found to occur in 0.19% or 1:537 (95% confidence interval 1:314-1:1008) hysterectomies for benign indications in our population. PRéCIS: Occult endometrial carcinomas are found to occur in 1:537 (0.19%) hysterectomies for benign indications. Copyright © 2018 Elsevier B.V. All rights reserved.

Defining the extent of cables loss in endometrial cancer subtypes and its effectiveness as an inhibitor of cell proliferation in malignant endometrial cells in vitro and in vivo.

PubMed

DeBernardo, Robert L; Littell, Ramey D; Luo, Hongwei; Duska, Linda R; Oliva, Esther; Kirley, Sandra D; Lynch, Maureen P; Zukerberg, Lawrence R; Rueda, Bo R

2005-01-01

Loss of Cables expression is associated with a high incidence of endometrial hyperplasia and endometrial adenocarcinoma in humans. The Cables mutant mouse develops endometrial hyperplasia and following exposure to chronic estrogen develops early endometrial adenocarcinoma. The objectives of the current study were to determine if: (1) loss of Cables expression occurred in high grade endometrioid adenocarcinoma, uterine serous and clear cell carcinoma as observed in endometrial hyperplasia and low grade endometrial adenocarcinoma; (2) overexpression of Cables inhibited cell proliferation in endometrial cancer (EC) cells in vitro and in vivo; and (3) progesterone could regulate the expression of Cables mRNA. Hyperplastic endometrium and low and high grade endometrioid adenocarcinoma showed loss of Cables expression when compared to benign control secretory endometrium. Loss of Cables expression in serous and clear cell tumors was similar to that observed in endometrioid adenocarcinomas with greater than 80% showing loss of protein expression. Treatment of EC lines with progesterone increased cables expression in low-grade EC whereas it had no effect on cables expression in cells derived from high-grade EC. The progesterone-induced increase in cables was abrogated in the presence of a progesterone receptor (PR) antagonist, suggesting the PR mediates the increase. Cables overexpression inhibited cell proliferation of well differentiated EC cells and had no effect on the poorly differentiated EC cells. The capacity to form tumors was dramatically reduced in the Cables overexpressing cell lines compared to those cells containing the control vector. Collectively these results suggest that Cables is an important regulator of cell proliferation and loss of Cables expression contributes to the development of all types of EC.

Combined analysis of endometrial thickness and pattern in predicting outcome of in vitro fertilization and embryo transfer: a retrospective cohort study.

PubMed

Chen, Shi-Ling; Wu, Fang-Rong; Luo, Chen; Chen, Xin; Shi, Xiao-Yun; Zheng, Hai-Yan; Ni, Yun-Ping

2010-03-24

To evaluate the combined effect of endometrial thickness and pattern on clinical outcome in patients undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET). Cycles of IVF/ICSI-ET conducted between January 2003 and December 2008 at a university-based reproductive center were reviewed retrospectively. Endometrial ultrasonographic characteristics were recorded on the day of hCG administration. In the combined analysis, endometrial thickness groups (group 1: equal or <7 mm; group 2: 7-14 mm; group 3: >14 mm) were subdivided into two endometrial patterns (pattern A: triple-line; pattern B: no-triple line). Clinical pregnancy rate (CPR) and early miscarriage rate in different groups were analyzed. A total of 2896 cycles were reviewed. Clinical pregnancy rate (CPR) was 24.4% in group 1-A. There were no second trimester pregnancies in group 1-B. Miscarriage rate in group 2-A was significantly lower compared to group 2-B (P < 0.01), although CPR did not show any significant differences between the groups. A no-triple line endometrial pattern with moderate endometrial thickness (7-14 mm) had a detrimental effect on pregnancy outcome, but not the occurrence of pregnancy. In group 3, there was no difference in CPR and miscarriage rates between the two patterns; adequate endometrial thickness (>14 mm) seemed to mitigate the detrimental impact (high miscarriage rate) of pattern B. Combined analysis of endometrial thickness and pattern on the day of hCG administration was a better predictor of the outcome of IVF/ICSI-ET and may be more helpful for patient counseling than the separate analyses.

Intentional Weight Loss and Endometrial Cancer Risk.

PubMed

Luo, Juhua; Chlebowski, Rowan T; Hendryx, Michael; Rohan, Thomas; Wactawski-Wende, Jean; Thomson, Cynthia A; Felix, Ashley S; Chen, Chu; Barrington, Wendy; Coday, Mace; Stefanick, Marcia; LeBlanc, Erin; Margolis, Karen L

2017-04-10

Purpose Although obesity is an established endometrial cancer risk factor, information about the influence of weight loss on endometrial cancer risk in postmenopausal women is limited. Therefore, we evaluated associations among weight change by intentionality with endometrial cancer in the Women's Health Initiative (WHI) observational study. Patients and Methods Postmenopausal women (N = 36,794) ages 50 to 79 years at WHI enrollment had their body weights measured and body mass indices calculated at baseline and at year 3. Weight change during that period was categorized as follows: stable (change within ± 5%), loss (change ≥ 5%), and gain (change ≥ 5%). Weight loss intentionality was assessed via self-report at year 3; change was characterized as intentional or unintentional. During the subsequent 11.4 years (mean) of follow-up, 566 incident endometrial cancer occurrences were confirmed by medical record review. Multivariable Cox proportional hazards regression models were used to evaluate relationships (hazard ratios [HRs] and 95% CIs) between weight change and endometrial cancer incidence. Results In multivariable analyses, compared with women who had stable weight (± 5%), women with weight loss had a significantly lower endometrial cancer risk (HR, 0.71; 95% CI, 0.54 to 0.95). The association was strongest among obese women with intentional weight loss (HR, 0.44; 95% CI, 0.25 to 0.78). Weight gain (≥ 10 pounds) was associated with a higher endometrial cancer risk than was stable weight, especially among women who had never used hormones. Conclusion Intentional weight loss in postmenopausal women is associated with a lower endometrial cancer risk, especially among women with obesity. These findings should motivate programs for weight loss in obese postmenopausal women.

Insulin/IGF and sex hormone axes in human endometrium and associations with endometrial cancer risk factors.

PubMed

Merritt, Melissa A; Strickler, Howard D; Einstein, Mark H; Yang, Hannah P; Sherman, Mark E; Wentzensen, Nicolas; Brouwer-Visser, Jurriaan; Cossio, Maria Jose; Whitney, Kathleen D; Yu, Herbert; Gunter, Marc J; Huang, Gloria S

2016-06-01

Experimental and observational data link insulin, insulin-like growth factor (IGF), and estrogens to endometrial tumorigenesis. However, there are limited data regarding insulin/IGF and sex hormone axes protein and gene expression in normal endometrial tissues, and very few studies have examined the impact of endometrial cancer risk factors on endometrial tissue biology. We evaluated endometrial tissues from 77 premenopausal and 30 postmenopausal women who underwent hysterectomy for benign indications and had provided epidemiological data. Endometrial tissue mRNA and protein levels were measured using quantitative real-time PCR and immunohistochemistry, respectively. In postmenopausal women, we observed higher levels of phosphorylated IGF-I/insulin receptor (pIGF1R/pIR) in diabetic versus non-diabetic women (p value =0.02), while women who reported regular nonsteroidal anti-inflammatory drug use versus no use had higher levels of insulin and progesterone receptors (both p values ≤0.03). We also noted differences in pIGF1R/pIR staining with OC use (postmenopausal women only), and the proportion of estrogen receptor-positive tissues varied by the number of live births and PTEN status (premenopausal only) (p values ≤0.04). Compared to premenopausal proliferative phase women, postmenopausal women exhibited lower mRNA levels of IGF1, but higher IGFBP1 and IGFBP3 expression (all p values ≤0.004), and higher protein levels of the receptors for estrogen, insulin, and IGF-I (all p values ≤0.02). Conversely, pIGF1R/pIR levels were higher in premenopausal proliferative phase versus postmenopausal endometrium (p value =0.01). These results highlight links between endometrial cancer risk factors and mechanistic factors that may contribute to early events in the multistage process of endometrial carcinogenesis.

POLE Proofreading Mutations Elicit an Antitumor Immune Response in Endometrial Cancer.

PubMed

van Gool, Inge C; Eggink, Florine A; Freeman-Mills, Luke; Stelloo, Ellen; Marchi, Emanuele; de Bruyn, Marco; Palles, Claire; Nout, Remi A; de Kroon, Cor D; Osse, Elisabeth M; Klenerman, Paul; Creutzberg, Carien L; Tomlinson, Ian Pm; Smit, Vincent Thbm; Nijman, Hans W; Bosse, Tjalling; Church, David N

2015-07-15

Recent studies have shown that 7% to 12% of endometrial cancers are ultramutated due to somatic mutation in the proofreading exonuclease domain of the DNA replicase POLE. Interestingly, these tumors have an excellent prognosis. In view of the emerging data linking mutation burden, immune response, and clinical outcome in cancer, we investigated whether POLE-mutant endometrial cancers showed evidence of increased immunogenicity. We examined immune infiltration and activation according to tumor POLE proofreading mutation in a molecularly defined endometrial cancer cohort including 47 POLE-mutant tumors. We sought to confirm our results by analysis of RNAseq data from the TCGA endometrial cancer series and used the same series to examine whether differences in immune infiltration could be explained by an enrichment of immunogenic neoepitopes in POLE-mutant endometrial cancers. Compared with other endometrial cancers, POLE mutants displayed an enhanced cytotoxic T-cell response, evidenced by increased numbers of CD8(+) tumor-infiltrating lymphocytes and CD8A expression, enrichment for a tumor-infiltrating T-cell gene signature, and strong upregulation of the T-cell cytotoxic differentiation and effector markers T-bet, Eomes, IFNG, PRF, and granzyme B. This was accompanied by upregulation of T-cell exhaustion markers, consistent with chronic antigen exposure. In silico analysis confirmed that POLE-mutant cancers are predicted to display more antigenic neoepitopes than other endometrial cancers, providing a potential explanation for our findings. Ultramutated POLE proofreading-mutant endometrial cancers are characterized by a robust intratumoral T-cell response, which correlates with, and may be caused by an enrichment of antigenic neopeptides. Our study provides a plausible mechanism for the excellent prognosis of these cancers. ©2015 American Association for Cancer Research.

Progestin and estrogen potency of combination oral contraceptives and endometrial cancer risk.

PubMed

Maxwell, G L; Schildkraut, J M; Calingaert, B; Risinger, J I; Dainty, L; Marchbanks, P A; Berchuck, A; Barrett, J C; Rodriguez, G C

2006-11-01

Using data from a case-control study of endometrial cancer, we investigated the relationship between the progestin and estrogen potency in combination oral contraceptives (OCs) and the risk of developing endometrial cancer. Subjects included 434 endometrial cancer cases and 2,557 controls identified from the Cancer and Steroid Hormone (CASH) study. OCs were classified into four categories according to the individual potencies of each hormonal constituent (high versus low estrogen or progestin potency). Logistic regression was used to evaluate associations between endometrial cancer risk and combination OC formulations. With non-users as the referent group, use of OCs with either high potency progestin [odds ratio for endometrial cancer (OR)=0.21, 95% confidence interval (CI)=0.10 to 0.43] or with low potency progestin (OR=0.39, 95% CI=0.25 to 0.60) were both associated with a decreased risk of endometrial cancer. Overall high progestin potency OCs did not confer significantly more protection than low progestin potency OCs (OR=0.52, 95% CI=0.24 to 1.14). However, among women with a body mass index of 22.1 kg/m2 or higher, those who used high progestin potency oral contraceptives had a lower risk of endometrial cancer than those who used low progestin potency oral contraceptives (OR=0.31, 95% CI=0.11 to 0.92) while those with a BMI below 22.1 kg/m2 did not (OR=1.36, 95% CI=0.39 to 4.70). The potency of the progestin in most OCs appears adequate to provide a protective effect against endometrial cancer. Higher progestin-potency OCs may be more protective than lower progestin potency OCs among women with a larger body habitus.

Mucin genes (MUC2, MUC4, MUC5AC, and MUC6) detection in normal and pathological endometrial tissues.

PubMed

Alameda, Francesc; Mejías-Luque, Raquel; Garrido, Marta; de Bolós, Carme

2007-01-01

Changes in the composition and physical properties of the mucous gel covering the endometrial surface are detected during the menstrual cycle and in pathological conditions. The aim of this study is to analyze the expression patterns of the 11p15 secreted mucins, MUC2, MUC5AC, and MUC6, and the membrane-bound mucin MUC4 in proliferative and secretory normal endometrium, simple and complex hyperplasia, and endometrial adenocarcinoma. A total of 98 samples, 19 of normal endometrium (11 proliferative and 8 secretor), 44 of endometrial hyperplasia (23 simple, 21 complex), and 35 of endometrial endometrioid adenocarcinomas were analyzed by immunohistochemical techniques using specific antimucin antibodies. In the endometrial proliferative glandular epithelium, only MUC4 is detected (36.3% cases). During the secretory phase, increased levels of MUC2 are found (37.5%), whereas MUC4 is less detected (12.5%). In simple hyperplasia, higher levels of mucins are expressed in the endometrial glands: MUC2 is detected in 8.7%, MUC4 in 43.4%, and MUC5AC and MUC6 in 13% of the samples, whereas in complex hyperplasia, decreased levels of mucin expression are found: MUC2 and MUC5AC are not detected, and MUC4 (28.5%) and MUC6 (20.4%) are positive. In endometrial adenocarcinoma, MUC4 is highly detected (77.1%) and increased levels of MUC5AC and MUC6 are found (61.7% and 48.5%), whereas MUC2 is poorly detected (8.5%). These findings suggest that during endometrial neoplasic transformation, increased levels of MUC4, MUC5AC, and MUC6 are detected, whereas MUC2 is only significantly detected in the secretory endometrium.

Hypermethylation of miR-203 in endometrial carcinomas.

PubMed

Huang, Yi-Wen; Kuo, Chieh-Ti; Chen, Jo-Hsin; Goodfellow, Paul J; Huang, Tim H-M; Rader, Janet S; Uyar, Denise S

2014-05-01

Aberrant expression of SOX4 in endometrial cancer has been identified and partially was contributed to hypermethylation of miR-129-2. Other miRNAs are suspected to influence SOX 4 as well. The current study seeks to identify other hypermethylated miRNAs that regulate SOX4 in endometrial carcinomas. Methylation levels of miRNA promoter regions were measured by combined bisulfite restriction analysis (COBRA) and pyrosequencing assays. Gene expression was determined by RT-qPCR. Methylation level of a miRNA locus was corrected with clinicopathologic factors for 252 gynecological specimens. In silico analysis identified 13 miRNA loci bound on the 3'-UTR of SOX4. Using COBRA assays, increased methylation of miR-203, miR-219-2, miR-596, and miR-618 was detected in endometrial cancer cells relative to those seen in a normal cell line and in normal endometrium. Transfection of a miR-203 mimic decreased SOX4 gene expression. Hypermethylation of miR-203 was detected in 52% of type I endometrioid endometrial carcinomas (n=131) but was not seen in any of 10 uninvolved normal endometria (P<0.001). Methylation status of miR-203 was significantly associated with microsatellite instability and MLH1 methylation in endometrial tumors (P<0.001). Furthermore, hypermethylation of miR-203 was found in endometrioid and clear endometrial subtype tumors, but not in cervical squamous cell and ovarian carcinomas. Hypermethylation of miR-203 is a frequent event in endometrial carcinomas and is strongly associated with microsatellite instability and MLH1 methylation status. Thus, miR-203 methylation level might represent a marker for patients with endometrioid and clear endometrial sub-cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

Accuracy of Endometrial Sampling in Endometrial Carcinoma: A Systematic Review and Meta-analysis.

PubMed

Visser, Nicole C M; Reijnen, Casper; Massuger, Leon F A G; Nagtegaal, Iris D; Bulten, Johan; Pijnenborg, Johanna M A

2017-10-01

To assess the agreement between preoperative endometrial sampling and final diagnosis for tumor grade and subtype in patients with endometrial carcinoma. MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane library were searched from inception to January 1, 2017, for studies that compared tumor grade and histologic subtype in preoperative endometrial samples and hysterectomy specimens. In eligible studies, the index test included office endometrial biopsy, hysteroscopic biopsy, or dilatation and curettage; the reference standard was hysterectomy. Outcome measures included tumor grade, histologic subtype, or both. Two independent reviewers assessed the eligibility of the studies. Risk of bias was assessed (Quality Assessment of Diagnostic Accuracy Studies). A total of 45 studies (12,459 patients) met the inclusion criteria. The pooled agreement rate on tumor grade was 0.67 (95% CI 0.60-0.75) and Cohen's κ was 0.45 (95% CI 0.34-0.55). Agreement between hysteroscopic biopsy and final diagnosis was higher (0.89, 95% CI 0.80-0.98) than for dilatation and curettage (0.70, 95% CI 0.60-0.79; P=.02); however, it was not significantly higher than for office endometrial biopsy (0.73, 95% CI 0.60-0.86; P=.08). The lowest agreement rate was found for grade 2 carcinomas (0.61, 95% CI 0.53-0.69). Downgrading was found in 25% and upgrading was found in 21% of the endometrial samples. Agreement on histologic subtypes was 0.95 (95% CI 0.94-0.97) and 0.81 (95% CI 0.69-0.92) for preoperative endometrioid and nonendometrioid carcinomas, respectively. Overall there is only moderate agreement on tumor grade between preoperative endometrial sampling and final diagnosis with the lowest agreement for grade 2 carcinomas.

Intentional Weight Loss and Endometrial Cancer Risk

PubMed Central

Chlebowski, Rowan T.; Hendryx, Michael; Rohan, Thomas; Wactawski-Wende, Jean; Thomson, Cynthia A.; Felix, Ashley S.; Chen, Chu; Barrington, Wendy; Coday, Mace; Stefanick, Marcia; LeBlanc, Erin; Margolis, Karen L.

2017-01-01

Purpose Although obesity is an established endometrial cancer risk factor, information about the influence of weight loss on endometrial cancer risk in postmenopausal women is limited. Therefore, we evaluated associations among weight change by intentionality with endometrial cancer in the Women’s Health Initiative (WHI) observational study. Patients and Methods Postmenopausal women (N = 36,794) ages 50 to 79 years at WHI enrollment had their body weights measured and body mass indices calculated at baseline and at year 3. Weight change during that period was categorized as follows: stable (change within ± 5%), loss (change ≥ 5%), and gain (change ≥ 5%). Weight loss intentionality was assessed via self-report at year 3; change was characterized as intentional or unintentional. During the subsequent 11.4 years (mean) of follow-up, 566 incident endometrial cancer occurrences were confirmed by medical record review. Multivariable Cox proportional hazards regression models were used to evaluate relationships (hazard ratios [HRs] and 95% CIs) between weight change and endometrial cancer incidence. Results In multivariable analyses, compared with women who had stable weight (± 5%), women with weight loss had a significantly lower endometrial cancer risk (HR, 0.71; 95% CI, 0.54 to 0.95). The association was strongest among obese women with intentional weight loss (HR, 0.44; 95% CI, 0.25 to 0.78). Weight gain (≥ 10 pounds) was associated with a higher endometrial cancer risk than was stable weight, especially among women who had never used hormones. Conclusion Intentional weight loss in postmenopausal women is associated with a lower endometrial cancer risk, especially among women with obesity. These findings should motivate programs for weight loss in obese postmenopausal women. PMID:28165909

Endometrial carcinoma in a 15-year-old obese patient with persistent uterine bleeding.

PubMed

Liu, Guoyan; Wang, Yingmei; Zhang, Xuhong; Yuan, Bibo; Han, Cha; Xue, Fengxia

2014-04-01

Endometrial carcinoma is the most common malignancy of the upper female genital tract but is rare in teenagers. Here, we report the case of a 15-year-old, nulliparous, morbidly obese female with complaints of asthenia and menometrorrhagia lasting for six months. On examination, the patient had an enlarged uterus approximately 14 gestational weeks in size, and ultrasound revealed an intrauterine mass and polycystic ovaries. An endometrial biopsy performed during hysteroscopy revealed endometrioid adenocarcinoma, and magnetic resonance imaging showed myometrial invasion. The patient underwent a laparotomy involving total abdominal hysterectomy, right salpingo-oophorectomy, wedge-shape dissection of the left ovary, and pelvic and para-aortic lymphadenectomy. We analyze the pathogenesis of endometrial carcinoma in this case and discuss the risk factors for endometrial carcinoma, especially in young women. Gynecologists should be vigilant for persistent abnormal uterine bleeding and other signs of endometrial carcinoma in young women, especially those who have risk factors for the disease.

Endometrial stromal tumours revisited: an update based on the 2014 WHO classification.

PubMed

Ali, Rola H; Rouzbahman, Marjan

2015-05-01

Endometrial stromal tumours (EST) are rare tumours of endometrial stromal origin that account for less than 2% of all uterine tumours. Recent cytogenetic and molecular advances in this area have improved our understanding of ESTs and helped refine their classification into more meaningful categories. Accordingly, the newly released 2014 WHO classification system recognises four categories: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LGESS), high-grade endometrial stromal sarcoma (HGESS) and undifferentiated uterine sarcoma (UUS). At the molecular level, these tumours may demonstrate a relatively simple karyotype with a defining chromosomal rearrangement (as in the majority of ESNs, LGESSs and YWHAE-rearranged HGESS) or demonstrate complex cytogenetic aberrations lacking specific rearrangements (as in UUSs). Herein we provide an update on this topic aimed at the practicing pathologist. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Equine endometrial fibrosis correlates with 11beta-HSD2, TGF-beta1 and ACE activities.

PubMed

Ganjam, V K; Evans, T J

2006-03-27

Endometrial periglandular fibrosis (EPF) contributes to embryonic and fetal loss in mares. Equine EPF correlates inversely with conception and successful gestation. In the modified Kenney endometrial biopsy classification system, EPF categories I, IIA, IIB, and III correspond to minimal, mild, moderate, and severe fibrosis (+/-inflammation), respectively. Paraffin sections of biopsy specimens were stained with H&E, and picrosirius red (specific for fibrillar collagens types I and III), to determine %EPCVF. Endometrial ACE-binding activity, TGF-beta1 and 11beta-HSD2 activities were also measured. Ultrastructural changes in EPF categories IIB and III endometria strongly suggested myofibroblastic transformation. ACE-binding activity was highest in EPF category IIB; however, endometrial TGF-beta1 and 11beta-HSD2 activities were significantly correlated to the severity of EPF (P<0.05). We conclude that, locally generated angiotensin II initiates the expression of TGF-beta1 resulting in myofibroblastic transformation. 11Beta-HSD2 in concert appears to modulate the severity of endometrial fibrosis.

Epigenetics and genetics in endometrial cancer: new carcinogenic mechanisms and relationship with clinical practice.

PubMed

Banno, Kouji; Kisu, Iori; Yanokura, Megumi; Masuda, Kenta; Ueki, Arisa; Kobayashi, Yusuke; Susumu, Nobuyuki; Aoki, Daisuke

2012-04-01

Endometrial cancer is the seventh most common cancer worldwide among females. An increased incidence and a younger age of patients are also predicted to occur, and therefore elucidation of the pathological mechanisms is important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, epigenetic mechanisms have been examined. Silencing of genes by DNA hypermethylation, hereditary epimutation of DNA mismatch repair genes and regulation of gene expression by miRNAs may underlie carcinogenesis in endometrial cancer. New therapies include targeting epigenetic changes using histone deacetylase inhibitors. Some cases of endometrial cancer may also be hereditary. Thus, patients with Lynch syndrome which is a hereditary disease, have a higher risk for developing endometrial cancer than the general population. Identification of such disease-related genes may contribute to early detection and prevention of endometrial cancer.

Molecular approaches for classifying endometrial carcinoma.

PubMed

Piulats, Josep M; Guerra, Esther; Gil-Martín, Marta; Roman-Canal, Berta; Gatius, Sonia; Sanz-Pamplona, Rebeca; Velasco, Ana; Vidal, August; Matias-Guiu, Xavier

2017-04-01

Endometrial carcinoma is the most common cancer of the female genital tract. This review article discusses the usefulness of molecular techniques to classify endometrial carcinoma. Any proposal for molecular classification of neoplasms should integrate morphological features of the tumors. For that reason, we start with the current histological classification of endometrial carcinoma, by discussing the correlation between genotype and phenotype, and the most significant recent improvements. Then, we comment on some of the possible flaws of this classification, by discussing also the value of molecular pathology in improving them, including interobserver variation in pathologic interpretation of high grade tumors. Third, we discuss the importance of applying TCGA molecular approach to clinical practice. We also comment on the impact of intratumor heterogeneity in classification, and finally, we will discuss briefly, the usefulness of TCGA classification in tailoring immunotherapy in endometrial cancer patients. We suggest combining pathologic classification and the surrogate TCGA molecular classification for high-grade endometrial carcinomas, as an option to improve assessment of prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Hypoxia and hypoxia inducible factor-1α are required for normal endometrial repair during menstruation.

PubMed

Maybin, Jacqueline A; Murray, Alison A; Saunders, Philippa T K; Hirani, Nikhil; Carmeliet, Peter; Critchley, Hilary O D

2018-01-23

Heavy menstrual bleeding (HMB) is common and debilitating, and often requires surgery due to hormonal side effects from medical therapies. Here we show that transient, physiological hypoxia occurs in the menstrual endometrium to stabilise hypoxia inducible factor 1 (HIF-1) and drive repair of the denuded surface. We report that women with HMB have decreased endometrial HIF-1α during menstruation and prolonged menstrual bleeding. In a mouse model of simulated menses, physiological endometrial hypoxia occurs during bleeding. Maintenance of mice under hyperoxia during menses decreases HIF-1α induction and delays endometrial repair. The same effects are observed upon genetic or pharmacological reduction of endometrial HIF-1α. Conversely, artificial induction of hypoxia by pharmacological stabilisation of HIF-1α rescues the delayed endometrial repair in hypoxia-deficient mice. These data reveal a role for HIF-1 in the endometrium and suggest its pharmacological stabilisation during menses offers an effective, non-hormonal treatment for women with HMB.

Thin endometrium in donor oocyte recipients: enigma or obstacle for implantation?

PubMed

Dain, Lena; Bider, David; Levron, Jacob; Zinchenko, Viktor; Westler, Sharon; Dirnfeld, Martha

2013-11-01

To evaluate the combined effect of endometrial thickness and anatomic uterine factors on clinical outcome in oocyte donation recipients. Retrospective analysis of oocyte donation cycles conducted between 2005 and 2010. Two private IVF centers. A total of 737 donor oocyte cycles. None. Clinical pregnancy and live birth rates. No statistically significant difference was found in clinical pregnancy rates and live birth rates in cycles with endometrial thickness <6 mm compared with those with endometrial thickness >10 mm. However, a relatively high rate of live births was found within a medium range of endometrial thickness (8.2-10 mm). All intrauterine adhesion cases occurred in cycles with thinner endometrium. No statistically significant difference was found in clinical pregnancy rates and live birth rates in cycles with endometrial thickness <6 mm compared with those with thickness >6 mm. A relatively high rate of live births was found within a medium range of endometrial thickness (9.1-10 mm). Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Progesterone-dependent Regulation of Endometrial Cannabinoid Receptor Type 1 (CB1-R) Expression is Disrupted in Women with Endometriosis and in Isolated Stromal Cells Exposed to TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)

PubMed Central

Resuehr, David; Glore, Dana R.; Taylor, Hugh S.; Bruner-Tran, Kaylon L.; Osteen, Kevin G.

2012-01-01

Objective To examine the differentiation-related expression of CB1-R mRNA and protein in endometrial tissue obtained from women with and without endometriosis and to determine the impact of acute TCDD exposure on CB1-R gene expression in isolated endometrial stromal cells. Design Laboratory-based study Setting University-affiliated medical center Patients Women with and without endometriosis undergoing volunteer endometrial biopsies after informed consent. Interventions None Main Outcome Measures Analysis of in vivo CB1-R mRNA and protein expression in human endometrial tissues and mRNA expression in isolated stromal cells following exposure to TCDD or a progesterone receptor antagonist (Onapristone). Results CB1-R mRNA and protein expression was highest during the progesterone-dominated secretory phase in control women, while expression was minimal in endometrial tissues acquired from women with endometriosis, regardless of the cycle phase. Although progesterone was found to induce CB1-R mRNA expression in endometrial stromal cells from control donors, steroid-induced expression of this gene was inhibited by co-treatment with either TCDD or Onapristone. Conclusions Our studies reveal a role for the anti-inflammatory actions of progesterone in regulating endometrial cannabinoid signaling, which is disrupted in women with endometriosis. Significantly, our studies demonstrate, for the first time, that acute TCDD exposure disrupts cannabinoid signaling in the human endometrium. PMID:22789143

Endometrial cancer: magnetic resonance imaging.

PubMed

Manfredi, R; Gui, B; Maresca, G; Fanfani, F; Bonomo, L

2005-01-01

Carcinoma of the endometrium is the most common invasive gynecologic malignancy of the female genital tract. Clinically, patients with endometrial carcinoma present with abnormal uterine bleeding. The role of magnetic resonance imaging (MRI) in endometrial carcinoma is disease staging and treatment planning. MRI has been shown to be the most valuable imaging mod-ality in this task, compared with endovaginal ultrasound and computed tomography, because of its intrinsic contrast resolution and multiplanar capability. MRI protocol includes axial T1-weighted images; axial, sagittal, and coronal T2-weighted images; and dynamic gadolinium-enhanced T1-weighted imaging. MR examination is usually performed in the supine position with a phased array multicoil using a four-coil configuration. Endometrial carcinoma is isointense with the normal endometrium and myometrium on noncontrast T1-weighted images and has a variable appearance on T2-weighted images demonstrating heterogeneous signal intensity. The appearance of noninvasive endometrial carcinoma on MRI is characterized by a normal or thickened endometrium, with an intact junctional zone and a sharp tumor-myometrium interface. Invasive endometrial carcinoma is characterized disruption or irregularity of the junctional zone by intermediate signal intensity mass on T2-weighted images. Invasion of the cervical stroma is diagnosed when the low signal intensity cervical stroma is disrupted by the higher signal intensity endometrial carcinoma. MRI in endometrial carcinoma performs better than other imaging modalities in disease staging and treatment planning. Further, the accuracy and the cost of MRI are equivalent to those of surgical staging.

Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis.

PubMed

Takeda, Takashi; Banno, Kouji; Yanokura, Megumi; Adachi, Masataka; Iijima, Moito; Kunitomi, Haruko; Nakamura, Kanako; Iida, Miho; Nogami, Yuya; Umene, Kiyoko; Masuda, Kenta; Kobayashi, Yusuke; Yamagami, Wataru; Hirasawa, Akira; Tominaga, Eiichiro; Susumu, Nobuyuki; Aoki, Daisuke

2016-10-14

Germline mutation of DNA mismatch repair (MMR) genes is a cause of Lynch syndrome. Methylation of MutL homolog 1 ( MLH1 ) and MutS homolog 2 ( MSH2 ) has been detected in peripheral blood cells of patients with colorectal cancer. This methylation is referred to as epimutation. Methylation of these genes has not been studied in an unselected series of endometrial cancer cases. Therefore, we examined methylation of MLH1 , MSH2 , and MSH6 promoter regions of peripheral blood cells in 206 patients with endometrial cancer using a methylation-specific polymerase chain reaction (MSP). Germline mutation of MMR genes, microsatellite instability (MSI), and immunohistochemistry (IHC) were also analyzed in each case with epimutation. MLH1 epimutation was detected in a single patient out of a total of 206 (0.49%)-1 out of 58 (1.72%) with an onset age of less than 50 years. The patient with MLH1 epimutation showed high level MSI (MSI-H), loss of MLH1 expression and had developed endometrial cancer at 46 years old, complicated with colorectal cancer. No case had epimutation of MSH2 or MSH6 . The MLH1 epimutation detected in a patient with endometrial cancer may be a cause of endometrial carcinogenesis. This result indicates that it is important to check epimutation in patients with endometrial cancer without a germline mutation of MMR genes.

Stromal p16 expression is significantly increased in endometrial carcinoma

PubMed Central

Yoon, Nara; Kim, Ji-Ye; Kim, Hyun-Soo

2017-01-01

p16 is a negative regulator of cell proliferation and is considered a tumor suppressor protein. Alterations in p16 protein expression are associated with tumor development and progression. However, the p16 expression status in the peritumoral stroma has not been investigated in the endometrium. Therefore, we evaluated stromal p16 expression in different types of endometrial lesions using immunohistochemistry. Differences in the p16 expression status according to the degree of malignancy and histological type were analyzed. This study included 62, 26, and 36 cases of benign, precancerous, and malignant endometrial lesions, respectively. Most benign lesions showed negative or weak expression, whereas precancerous lesions showed a variable degree of staining proportion and intensity. Atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) and serous endometrial intraepithelial carcinoma (SEIC) had significantly higher stromal p16 expression levels than benign lesions. Endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma showed significantly elevated stromal p16 expression levels compared with benign and precancerous lesions. In addition, there were significant differences in stromal p16 expression between AH/EIN and SEIC and between EC and SC. In contrast, differences in stromal p16 expression among nonpathological endometrium, atrophic endometrium, endometrial polyp, and hyperplasia without atypia were not statistically significant. Our observations suggest that stromal p16 expression is involved in the development and progression of endometrial carcinoma, and raise the possibility that p16 overexpression in the peritumoral stroma is associated with aggressive oncogenic behavior of endometrial SC. PMID:27902476

Nucleobindin 2 (NUCB2) in human endometrial carcinoma: a potent prognostic factor associated with cell proliferation and migration.

PubMed

Takagi, Kiyoshi; Miki, Yasuhiro; Tanaka, Sota; Hashimoto, Chiaki; Watanabe, Mika; Sasano, Hironobu; Ito, Kiyoshi; Suzuki, Takashi

2016-01-01

Nucleobindin 2 (NUCB2) is a multifunctional protein containing several functional domains, and associated with wide variety of biological process such as food intake and energy homeostasis. Recently, NUCB2 has been implicated in not only normal human tissues but also some kinds of human malignancies. However, its clinical and/or biological significance has largely remained unknown in endometrial carcinomas. We therefore immunolocalized NUCB2 protein in 87 endometrial carcinoma tissues and examined its clinical significance. NUCB2 immunoreactivity was detected in 19 out of 87 (22%) of endometrial carcinoma cases examined, and positively correlated with Ki67 labeling index, while there was no significant correlation between NUCB2 and stage, histological grade, and progesterone receptor status. Furthermore, NUCB2 immunoreactivity was significantly correlated with increased risk of recurrence and worse clinical outcome regardless of stage or histological grade. Subsequent multivariate analyses did reveal that NUCB2 immunoreactivity was an independent prognostic factor for both disease-free survival and endometrial cancer specific survival. In vitro experiments demonstrated that knockdown of NUCB2 using specific siRNA for NUCB2 significantly impaired cell proliferation and migration of the endometrial carcinoma cell lines, Ishikawa and Sawano cells, and that nesfatin-1 treatment significantly promoted cell proliferation and migration in Ishikawa cells. These findings possibly suggested that NUCB2 and/or nesfatin-1 had pivotal roles in the progression of endometrial carcinomas. Immunohistochemical NUCB2 status may therefore serve as a potent biomarker for endometrial carcinomas.

The evolution of endometrial carcinoma classification through application of immunohistochemistry and molecular diagnostics: past, present and future.

PubMed

Goebel, Emily A; Vidal, August; Matias-Guiu, Xavier; Blake Gilks, C

2017-12-12

Uterine cancer was first subclassified based on anatomic site, separating those tumours arising from the endometrium from cervical cancers. There was then further subclassification of endometrial cancers based on cell type, and this correlated with the Type I and Type II categories identified through the epidemiological studies of Bokhman, with endometrioid carcinoma corresponding (approximately) to Type I and serous carcinoma to Type II. These histotypes are not clearly separable in practice, however, with considerable interobserver variability in histotype diagnosis, especially for high-grade tumours. There followed studies of immunomarkers and then mutational studies of single genes, in attempts to improve subclassification. While these have revealed significant differences in protein expression and mutation profiles between endometrioid and serous carcinomas, there is also considerable overlap, so that there remain challenges in subclassification of endometrial carcinoma. Gene panel testing, using next-generation sequencing, was applied to endometrial cancers and highlighted that there are tumours that show genetic alterations intermediate between classic Type I/endometrioid and Type II/serous carcinomas. The Cancer Genome Atlas studies of endometrioid and serous carcinoma offered revolutionary insight into the subclassification of endometrial carcinoma, i.e. that there are four distinct categories of endometrial carcinoma, rather than two, based on genomic architecture. In this review, we provide an overview of immunohistochemical and molecular markers in endometrial carcinoma and comment on the important future directions in endometrial carcinoma subclassification arising from The Cancer Genome Atlas results.

Endometrial Adenocarcinoma Presenting in a Premenopausal Patient with Tuberous Sclerosis

ERIC Educational Resources Information Center

Jaffe, J. S.; Chambers, J. T.

2005-01-01

Background: Endometrial adenocarcinoma is very uncommon in women under 40 years of age. Case: A 39-year-old woman with tuberous sclerosis and severe intellectual disability presented with irregular bleeding unresponsive to oral contraceptive therapy. She was subsequently found to have a deeply invasive endometrial adenocarcinoma. Conclusion:…

Use of Outpatient Endometrial Biopsy in a Population with Intellectual Disability

ERIC Educational Resources Information Center

Jaffe, Joshua S.

2008-01-01

Background: To demonstrate the feasibility of outpatient endometrial sampling to evaluate abnormal uterine bleeding in a population of women with intellectual disability. Method: Retrospective chart review was completed of all endometrial biopsies performed on women attending a dedicated gynaecology clinic for women with intellectual disability…

Endometrial polyps in 2 African pygmy hedgehogs

PubMed Central

2005-01-01

Abstract Reports of spontaneously occurring endometrial polyps in animals are rare and have only involved a few species. This report is intended to advise veterinarians that older African pygmy hedgehogs may develop endometrial polyps and that these lesions can be a cause of bloody vaginal discharge, sometimes interpreted as hematuria. PMID:16048013

[Pneumothorax Caused by Multiple Pulmonary Metastases of a Uterine Endometrial Stromal Sarcoma;Report of a Case].

PubMed

Shomura, Shin; Suzuki, Hitoshi; Yada, Masaki; Kondo, Chiaki

2017-09-01

A 53-year-old woman who had undergone hystero-oophorectomy for uterine endometrial stromal sarcoma in our hospital 9 months previously was referred to our hospital because of bilateral pneumothorax. Chest computed tomography scan on admission revealed multiple thin-walled cavity nodules in both lung and a bilateral pneumothorax, suggesting pulmonary metastases of the uterine endometrial stromal sarcoma. We surgically treated the pneumothorax and diagnosed the nodules as metastatic lesions. They were pathologically diagnosed as metastatic uterine endometrial stromal sarcoma.

[The role of miRNA in endometrial cancer in the context of miRNA 205].

PubMed

Wilczyński, Miłosz; Danielska, Justyna; Dzieniecka, Monika; Malinowski, Andrzej

2015-11-01

MiRNAs are small, non-coding molecules of ribonucleic acids of approximately 22 bp length, which serve as regulators of gene expression and protein translation due to interference with messenger RNA (mRNA). MiRNAs, which take part in the regulation of cell cycle and apoptosis, may be associated with carcinogenesis. Aberrant expression of miRNAs in endometrial cancer might contribute to the endometrial cancer initiation or progression, as well as metastasis formation, and may influence cancer invasiveness. Specific-miRNAs expressed in endometrial cancer tissues may serve as diagnostic markers of the disease, prognostic biomarkers, or play an important part in oncological therapy We aimed to describe the role of miRNAs in endometrial cancer with special consideration of miRNA 205.

Infertility and incident endometrial cancer risk: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2).

PubMed

Yang, H P; Cook, L S; Weiderpass, E; Adami, H-O; Anderson, K E; Cai, H; Cerhan, J R; Clendenen, T V; Felix, A S; Friedenreich, C M; Garcia-Closas, M; Goodman, M T; Liang, X; Lissowska, J; Lu, L; Magliocco, A M; McCann, S E; Moysich, K B; Olson, S H; Petruzella, S; Pike, M C; Polidoro, S; Ricceri, F; Risch, H A; Sacerdote, C; Setiawan, V W; Shu, X O; Spurdle, A B; Trabert, B; Webb, P M; Wentzensen, N; Xiang, Y-B; Xu, Y; Yu, H; Zeleniuch-Jacquotte, A; Brinton, L A

2015-03-03

Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes. We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59-1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13-1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer. Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters.

Anti-Mullerian hormone and endometrial cancer: a multi-cohort study.

PubMed

Fortner, Renée T; Schock, Helena; Jung, Seungyoun; Allen, Naomi E; Arslan, Alan A; Brinton, Louise A; Egleston, Brian L; Falk, Roni T; Gunter, Marc J; Helzlsouer, Kathy J; Idahl, Annika; Johnson, Theron S; Kaaks, Rudolf; Krogh, Vittorio; Lundin, Eva; Merritt, Melissa A; Navarro, Carmen; Onland-Moret, N Charlotte; Palli, Domenico; Shu, Xiao-Ou; Sluss, Patrick M; Staats, Paul N; Trichopoulou, Antonia; Weiderpass, Elisabete; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Dorgan, Joanne F

2017-10-24

The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk. We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. Anti-Mullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (OR log2 ). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics. Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (OR log2 : 1.07 (0.99-1.17)), or with any of the examined subgroups. Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.

Persistence of an intact endometrial matrix and vessels structure in women exposed to VA-2914, a selective progesterone receptor modulator.

PubMed

Ravet, S; Munaut, C; Blacher, S; Brichant, G; Labied, S; Beliard, A; Chabbert-Buffet, N; Bouchard, P; Foidart, J-M; Pintiaux, A

2008-11-01

VA-2914 is a selective progesterone receptor modulator with potential contraceptive activity that induces amenorrhea, whereas progestins cause endometrial spotting and bleeding. This abnormal bleeding due to progestins is a consequence of focal stromal proteolysis by an increase in naked vessel size and density. Our objective was to quantify the effects of VA-2914 on endometrial vascularization, fibrillar matrix, and vascular endothelial growth factor (VEGF)-A expression in endometrial biopsies from 41 women before and after 12 wk daily treatment with a placebo, or 2.5, 5, or 10 mg VA-2914. Collagen fibrillar network was stained by silver impregnation. Vessel area, density, and structure were quantified with a computer-assisted image analysis system after double immunostaining using an anti-von Willebrand factor (endothelial cells) and an anti-alpha smooth muscle actin (vascular smooth muscle cells) marker antibody. VEGF-A mRNAs were quantified by RT-PCR and localized by immunohistochemistry. The endometrial vessels, collagen network, and mRNA levels of VEGF-A were identical during the luteal phase at baseline and in VA-2914 treated women. VEGF-A distribution was unchanged. VA-2914 does not alter the endometrial matrix and cells, and does not modify the endometrial vessel morphology as compared with baseline biopsies.

Oestrogen receptor-mediated expression of Olfactomedin 4 regulates the progression of endometrial adenocarcinoma

PubMed Central

Duan, Chao; Liu, Xubin; Liang, Shuang; Yang, Zheng; Xia, Meng; Wang, Liantang; Chen, Shangwu; Yu, Li

2014-01-01

Endometrial adenocarcinoma is the most common tumour of the female genital tract in developed countries, and oestrogen receptor (ER) signalling plays a pivotal role in its pathogenesis. When we used bioinformatics tools to search for the genes contributing to gynecological cancers, the expression of Olfactomedin 4 (OLFM4) was found by digital differential display to be associated with differentiation of endometrial adenocarcinoma. Aberrant expression of OLFM4 has been primarily reported in tumours of the digestive system. The mechanism of OLFM4 in tumuorigenesis is elusive. We investigated OLFM4 expression in endometrium, analysed the association of OLFM4 with ER signalling in endometrial adenocarcinoma, and examined the roles of OLFM4 in endometrial adenocarcinoma. Expression of OLFM4 was increased during endometrial carcinogenesis, linked to the differentiation of endometrioid adenocarcinoma, and positively related to the expression of oestrogen receptor-α (ERα) and progesterone receptor. Moreover, ERα-mediated signalling regulated expression of OLFM4, and knockdown of OLFM4 enhanced proliferation, migration and invasion of endometrial carcinoma cells. Down-regulation of OLFM4 was associated with decreased cumulative survival rate of patients with endometrioid adenocarcinoma. Our data suggested that impairment of ERα signal-mediated OLFM4 expression promoted the malignant progression of endometrioid adenocarcinoma, which may have significance for the therapy of this carcinoma. PMID:24495253

OVARIAN HILUS CELLS AND ENDOMETRIAL CARCINOMA WITH REFERENCE TO RADIATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ames, S.; Janovski, N.A.

1963-07-01

A survey of the relation of hilus cell genesis and frequency of detection in ovaries to adenocarcinoma of the endometrium is presented. Results were based on the examination of 281 ovaries obtained from patients with endometrial carcinoma. The results showed that there was no statistical difference between the occurrence of hilus cells in the endometrial carcinoma group and a control group (33 and 25% respectively). However, if mode of treatment was taken into consideration, and patients undergoing irradiation for endometrial adenocarcinoma prior to operation separated into an individual group, there was a significant difference in the distribution of hilus cellsmore » in those patients as compared with the nonirradiated carcinoma group, at the level of 5%. The radiotherapy in these cases consisisted mainly of 50100 mg intracavitary Ra for approximates 72 hr. A surprisingly high incidence (60%) of ovarian hilus cells was found in patients who underwent radioinduced menopause for benign gynecologic conditions prior to developing adenocarcinoma of the endometrium. The incidence in all postmenopausal patients was only 37%. Ovarian hilus cells were more prevalent in postmenopausal women irrespective of endometrial carcinoma. Premenopausal women with endometrial carcinoma who received no irradiation prior to definitive operation are, therefore, the ideal subjects for further investigation of the relation between endometrial adenocarcinoma and ovarian hilus cells. (BBB)« less

Mutational Analysis of Mismatch Repair Genes, hMLH1 and hMSH2, in Sporadic Endometrial Carcinomas with Microsatellite Instability

PubMed Central

Kobayashi, Kanji; Matsushima, Mieko; Koi, Sumiko; Saito, Hiroko; Sagae, Satoru; Kudo, Ryuichi

1996-01-01

Microsatellite instability, monitored by replication error (RER), bas been observed in both sporadic and hereditary types of endometrial carcinoma. In the hereditary tumors, this instability is considered to be caused by a germline defect in the DNA mismatch‐repair system. We previously reported that nearly one‐quarter of sporadic endometrial carcinomas examined revealed an RER‐positive phenotype at multiple microsatellite loci. To investigate the role of genetic alterations of DNA mismatch‐repair genes in sporadic endometrial carcinomas, we screened 18 RER(+) endometrial carcinomas for mutations of hMLH1 and hMSH2. Although we found no germline mutations, we detected two somatic mutations of hMLH1 in a single endometrial cancer; these two mutations had occurred on different alleles, suggesting that two separate mutational events had affected both copies of hMLH1 in this particular tumor. These data implied that mutations of hMLH1 or hMSH2 play limited roles in the development of sporadic endometrial carcinomas, and that the tumors with genetic instability might have alterations of other mismatch‐repair genes, such as hPMS1 and hPMS2, or of unknown genes related to the mismatch‐repair system. PMID:8609062

Association between macrophage migration inhibitory factor in the endometrium and estrogen in endometriosis

PubMed Central

ZHANG, XIAO; MU, LIN

2015-01-01

Recent studies have shown that macrophage migration inhibitory factor (MIF) has a possible role in endometriosis-related pain and infertility, yet it has not been explored whether the mRNA level of MIF is altered in endometrial tissues from patients with endometriosis. The aim of the present study was to compare the expression of MIF in endometrial tissues from women with and without endometriosis, and to analyze the association between endometrial MIF expression and 17β-estradiol (E2). The protein and mRNA expression of MIF in the human endometrial tissue was assessed by western blotting and reverse transcription-polymerase chain reaction analysis, respectively. The MIF expression of women with endometriosis was found to be significantly higher than that of the controls. A positive correlation was noted between the serum E2 level and MIF expression. In endometrial cells from women with endometriosis, the level of E2-induced MIF upregulation was significantly higher than that in cells from women without endometriosis. In conclusion, this study demonstrated a significant increase in MIF expression in the endometrial tissues of women with endometriosis and an association between MIF expression and E2 level. MIF expression in endometrial cells from patients with endometriosis showed an increased sensitivity to stimulation by E2. PMID:26622394

[Study on the peritoneal dissemination of endometrial cells during hysteroscopy].

PubMed

Duan, Hua; Li, Wei; Zhang, Ying; Zhao, Xia; Xia, En-Lan

2007-02-01

To study prospectively the likelihood and the affecting factors of endometrial cell dissemination into the peritoneal cavity during hysteroscopic procedures. A total of 121 patients with benign endometrial pathology underwent hysteroscopy combined with laparoscopy. All the patients had pelvic washings performed just before and after the procedure of hysteroscopy. We collected the peritoneal washings and analyzed the peritoneal cytology changes in both groups pre- and post-hysteroscopy, as well as the dissemination rate related to the time of hysteroscopy, the intrauterine distention pressure, the volume of distention media, and the feature of endometrial conditions. The ratio of positive endometrial cells in the peritoneal washings of post-hysteroscopy group was 51.2% (62/121), which was significantly higher than pre-hysteroscopy group, 38.0% (46/121) (P < 0.01). The mean operation time in the group of positive peritoneal cytology was (38 +/- 16) min, longer than the negative group (P < 0.05). However, there was no significant difference between the two groups with regard to the total volume of distention media, the distention pressure, and the endometrial feature (P > 0.05). Hysteroscopic procedures may have a risk of disseminating the endometrial cells into peritoneal cavity. Under a certain uterine distention pressure, the rate of dissemination is correlated with hysteroscopic duration.

Platelet-rich plasma as an adjuvant in the endometrial preparation of patients with refractory endometrium.

PubMed

Molina, Aixa; Sánchez, Jose; Sánchez, William; Vielma, Vanessa

2018-03-01

To improve endometrial quality and implantation rates after the administration of platelet-rich plasma in patients with refractory endometrium. 19 patients undergoing in vitro fertilization, aged between 33 and 45 years with a history of refractory endometrium, to whom platelet rich plasma was given by infusion with a catheter into the uterine cavity on the tenth day of the hormone replacement therapy, and then 72 hours after the first administration. Endometrial thicknesses >7mm was reported with the first use; and in all cases, endometrial thicknesses >9mm were evident after the second administration. The entire study group qualified for Embryo Transfer at the blastocyst stage. We had 73.7% of positive pregnancy tests, of which 26.3% yielded live births; 26.3% ongoing pregnancies; 10.5% biochemical pregnancies; 5.3% anembryonic pregnancies and 5.3% had fetal death (16 weeks). Platelet-rich plasma and its biostimulation effects on the endometrial microvasculature seems to be beneficial to patients with refractory endometrium, providing an increase in endometrial receptivity and a consequent increase in implantation rates. As an autologous resource, they are easy to obtain and inexpensive. Thus, we recommend it to be included in the different protocols for endometrial preparation, including those in which a natural cycle is preferred.

Platelet-rich plasma as an adjuvant in the endometrial preparation of patients with refractory endometrium

PubMed Central

Molina, Aixa; Sánchez, Jose; Sánchez, William; Vielma, Vanessa

2018-01-01

Objective To improve endometrial quality and implantation rates after the administration of platelet-rich plasma in patients with refractory endometrium. Methods 19 patients undergoing in vitro fertilization, aged between 33 and 45 years with a history of refractory endometrium, to whom platelet rich plasma was given by infusion with a catheter into the uterine cavity on the tenth day of the hormone replacement therapy, and then 72 hours after the first administration. Results Endometrial thicknesses >7mm was reported with the first use; and in all cases, endometrial thicknesses >9mm were evident after the second administration. The entire study group qualified for Embryo Transfer at the blastocyst stage. We had 73.7% of positive pregnancy tests, of which 26.3% yielded live births; 26.3% ongoing pregnancies; 10.5% biochemical pregnancies; 5.3% anembryonic pregnancies and 5.3% had fetal death (16 weeks). Conclusions Platelet-rich plasma and its biostimulation effects on the endometrial microvasculature seems to be beneficial to patients with refractory endometrium, providing an increase in endometrial receptivity and a consequent increase in implantation rates. As an autologous resource, they are easy to obtain and inexpensive. Thus, we recommend it to be included in the different protocols for endometrial preparation, including those in which a natural cycle is preferred. PMID:29303234

Similar protein expression profiles of ovarian and endometrial high-grade serous carcinomas.

PubMed

Hiramatsu, Kosuke; Yoshino, Kiyoshi; Serada, Satoshi; Yoshihara, Kosuke; Hori, Yumiko; Fujimoto, Minoru; Matsuzaki, Shinya; Egawa-Takata, Tomomi; Kobayashi, Eiji; Ueda, Yutaka; Morii, Eiichi; Enomoto, Takayuki; Naka, Tetsuji; Kimura, Tadashi

2016-03-01

Ovarian and endometrial high-grade serous carcinomas (HGSCs) have similar clinical and pathological characteristics; however, exhaustive protein expression profiling of these cancers has yet to be reported. We performed protein expression profiling on 14 cases of HGSCs (7 ovarian and 7 endometrial) and 18 endometrioid carcinomas (9 ovarian and 9 endometrial) using iTRAQ-based exhaustive and quantitative protein analysis. We identified 828 tumour-expressed proteins and evaluated the statistical similarity of protein expression profiles between ovarian and endometrial HGSCs using unsupervised hierarchical cluster analysis (P<0.01). Using 45 statistically highly expressed proteins in HGSCs, protein ontology analysis detected two enriched terms and proteins composing each term: IMP2 and MCM2. Immunohistochemical analyses confirmed the higher expression of IMP2 and MCM2 in ovarian and endometrial HGSCs as well as in tubal and peritoneal HGSCs than in endometrioid carcinomas (P<0.01). The knockdown of either IMP2 or MCM2 by siRNA interference significantly decreased the proliferation rate of ovarian HGSC cell line (P<0.01). We demonstrated the statistical similarity of the protein expression profiles of ovarian and endometrial HGSC beyond the organs. We suggest that increased IMP2 and MCM2 expression may underlie some of the rapid HGSC growth observed clinically.

[Value of ultrasonography to predict the endometrial cancer in postmenopausal bleeding].

PubMed

Bouzid, A; Ayachi, A; Mourali, M

2015-10-01

To build mathematical models for evaluating the individual risk of endometrial malignancy in women with postmenopausal bleeding and a thick endometrium using clinical data, sonographic endometrial thickness and power Doppler ultrasound findings. A total of 117 patients underwent transvaginal two-dimensional gray-scale and power Doppler ultrasound examination of the endometrium before getting endometrial biopsy. Inclusion criteria were post-menopausal bleeding and a thick endometrium greater than 5mm. The ultrasound image showing the most vascularized section through the endometrium as assessed by power Doppler was frozen to estimate endometrial thickness and features. The vascularity index was calculated using computer software. A structured history was taken to collect clinical information. Multivariate logistic regression analysis was used to create mathematical models to predict endometrial malignancy. There were 31 (26.4%) malignant and 86 (74.6%) benign endometria… Women with a malignant endometrium were older (median age 61 vs 56 years, P=0.036) and had a thicker endometrium (median thickness 18.8mm vs 12.5; P=0.002) and higher values for vascularity index. When using only clinical data to build a model for estimating the risk of endometrial malignancy, a model including the variables age had the largest area under the receiver-operating characteristics curve (AUC), with a value of 0.69 (95% confidence interval [CI], 0.59-0.79). A model including age and endometrial thickness had an AUC of 0.72 (95% CI, 0.50-0.96), and one including age, endometrial thickness and vascularity index had an AUC of 0.91 (95% CI, 0.62-0.97). Using a risk cut-off of 12%, the latter model had sensitivity 89%, specificity 74%, positive likelihood ratio 3.42 and negative likelihood ratio 0.14. Postmenopausal bleeding is a frequent cause of consultation in gynecological particularly in peri- or post-menopausal period. They are the main alarm sign of endometrial carcinoma. Vaginal ultrasound has become the "gold standard" in the initial exploration. It is a powerful tool to estimate the individual risk of malignancy in symptomatic postmenopausal women in order to optimize the management. The diagnostic performance of models predicting endometrial cancer increases substantially when sonographic and power Doppler information are added to clinical variables. This model seems to be clinically useful but need to be prospectively validated. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

mRNA-binding protein TIA-1 reduces cytokine expression in human endometrial stromal cells and is down-regulated in ectopic endometrium.

PubMed

Karalok, Hakan Mete; Aydin, Ebru; Saglam, Ozlen; Torun, Aysenur; Guzeloglu-Kayisli, Ozlem; Lalioti, Maria D; Kristiansson, Helena; Duke, Cindy M P; Choe, Gina; Flannery, Clare; Kallen, Caleb B; Seli, Emre

2014-12-01

Cytokines and growth factors play important roles in endometrial function and the pathogenesis of endometriosis. mRNAs encoding cytokines and growth factors undergo rapid turnover; primarily mediated by adenosine- and uridine-rich elements (AREs) located in their 3'-untranslated regions. T-cell intracellular antigen (TIA-1), an mRNA-binding protein, binds to AREs in target transcripts, leading to decreased gene expression. The purpose of this article was to determine whether TIA-1 plays a role in the regulation of endometrial cytokine and growth factor expression during the normal menstrual cycle and whether TIA-1 expression is altered in women with endometriosis. Eutopic endometrial tissue obtained from women without endometriosis (n = 30) and eutopic and ectopic endometrial tissues from women with endometriosis (n = 17) were immunostained for TIA-1. Staining intensities were evaluated by histological scores (HSCOREs). The regulation of endometrial TIA-1 expression by immune factors and steroid hormones was studied by treating primary cultured human endometrial stromal cells (HESCs) with vehicle, lipopolysaccharide, TNF-α, IL-6, estradiol, or progesterone, followed by protein blot analyses. HESCs were engineered to over- or underexpress TIA-1 to test whether TIA-1 regulates IL-6 or TNF-α expression in these cells. We found that TIA-1 is expressed in endometrial stromal and glandular cells throughout the menstrual cycle and that this expression is significantly higher in the perimenstrual phase. In women with endometriosis, TIA-1 expression in eutopic and ectopic endometrium was reduced compared with TIA-1 expression in eutopic endometrium of unaffected control women. Lipopolysaccharide and TNF-α increased TIA-1 expression in HESCs in vitro, whereas IL-6 or steroid hormones had no effect. In HESCs, down-regulation of TIA-1 resulted in elevated IL-6 and TNF-α expression, whereas TIA-1 overexpression resulted in decreased IL-6 and TNF-α expression. Endometrial TIA-1 is regulated throughout the menstrual cycle, TIA-1 modulates the expression of immune factors in endometrial cells, and downregulation of TIA-1 may contribute to the pathogenesis of endometriosis.

mRNA-Binding Protein TIA-1 Reduces Cytokine Expression in Human Endometrial Stromal Cells and Is Down-Regulated in Ectopic Endometrium

PubMed Central

Karalok, Hakan Mete; Aydin, Ebru; Saglam, Ozlen; Torun, Aysenur; Guzeloglu-Kayisli, Ozlem; Lalioti, Maria D.; Kristiansson, Helena; Duke, Cindy M. P.; Choe, Gina; Flannery, Clare; Kallen, Caleb B.

2014-01-01

Background: Cytokines and growth factors play important roles in endometrial function and the pathogenesis of endometriosis. mRNAs encoding cytokines and growth factors undergo rapid turnover; primarily mediated by adenosine- and uridine-rich elements (AREs) located in their 3′-untranslated regions. T-cell intracellular antigen (TIA-1), an mRNA-binding protein, binds to AREs in target transcripts, leading to decreased gene expression. Objective: The purpose of this article was to determine whether TIA-1 plays a role in the regulation of endometrial cytokine and growth factor expression during the normal menstrual cycle and whether TIA-1 expression is altered in women with endometriosis. Methods: Eutopic endometrial tissue obtained from women without endometriosis (n = 30) and eutopic and ectopic endometrial tissues from women with endometriosis (n = 17) were immunostained for TIA-1. Staining intensities were evaluated by histological scores (HSCOREs). The regulation of endometrial TIA-1 expression by immune factors and steroid hormones was studied by treating primary cultured human endometrial stromal cells (HESCs) with vehicle, lipopolysaccharide, TNF-α, IL-6, estradiol, or progesterone, followed by protein blot analyses. HESCs were engineered to over- or underexpress TIA-1 to test whether TIA-1 regulates IL-6 or TNF-α expression in these cells. Results: We found that TIA-1 is expressed in endometrial stromal and glandular cells throughout the menstrual cycle and that this expression is significantly higher in the perimenstrual phase. In women with endometriosis, TIA-1 expression in eutopic and ectopic endometrium was reduced compared with TIA-1 expression in eutopic endometrium of unaffected control women. Lipopolysaccharide and TNF-α increased TIA-1 expression in HESCs in vitro, whereas IL-6 or steroid hormones had no effect. In HESCs, down-regulation of TIA-1 resulted in elevated IL-6 and TNF-α expression, whereas TIA-1 overexpression resulted in decreased IL-6 and TNF-α expression. Conclusions: Endometrial TIA-1 is regulated throughout the menstrual cycle, TIA-1 modulates the expression of immune factors in endometrial cells, and downregulation of TIA-1 may contribute to the pathogenesis of endometriosis. PMID:25140393

Inhibition of Expression of the S100A8 Gene Encoding the S100 Calcium-Binding Protein A8 Promotes Apoptosis by Suppressing the Phosphorylation of Protein Kinase B (Akt) in Endometrial Carcinoma and HEC-1A Cells.

PubMed

Liu, Chang; Xing, Guangyang; Wu, Cailiang; Zhu, Jun; Wei, Min; Liu, Dajiang; Ge, Yan; Chen, Yao; Lei, Ting; Yang, Yongxiu

2018-03-29

BACKGROUND The aim of this study was to investigate the expression and silencing of the S100A8 gene, which encodes the S100 calcium-binding protein A8 (S100A8), and apoptosis and phosphorylation of protein kinase B (Akt) in tissue samples of endometrial carcinoma and HEC-1A endometrial adenocarcinoma cells in vitro. MATERIAL AND METHODS Immunohistochemistry (IHC) was used to detect expression of the S100A8 protein in 74 tissue samples of endometrial cancer and 22 normal endometrial tissue samples. A stable S100A8 gene knockdown cell line was constructed using lentiviral packing short hairpin RNA (shRNA) transfected into HEC-1A cells. S100A8 mRNA and S100A8 protein levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. The effects of expression of the S100A8 gene by endometrial cancer cells was investigated by the MTT assay, cell cycle and apoptotic assays, qRT-PCR, and Western blotting. RESULTS IHC showed high levels of expression of S100A8 protein in endometrial carcinoma tissues, and HEC-1A adenocarcinoma cells (in G1 and G2). Increased expression of S100A8 protein was found endometrial cancer tissues compared with normal endometrial tissues (79.7% vs. 4.5%). S100A8 gene knockdown reduced cell proliferation in the HEC-1A cells compared with control cells, induced cell apoptosis, inhibited the phosphorylation of protein kinase B (Akt), and induced the expression of pro-apoptotic genes, including the cytochrome C gene, CYCS, BAD, BAX, FOXO1, FOXO3, CASP9, and CASP3. CONCLUSIONS In endometrial carcinoma cells, down-regulation of the S100A8 gene induced cell apoptosis via inhibition of the phosphorylated or active form of protein kinase B (Akt).

Inhibition of Expression of the S100A8 Gene Encoding the S100 Calcium-Binding Protein A8 Promotes Apoptosis by Suppressing the Phosphorylation of Protein Kinase B (Akt) in Endometrial Carcinoma and HEC-1A Cells

PubMed Central

Liu, Chang; Xing, Guangyang; Wu, Cailiang; Zhu, Jun; Wei, Min; Liu, Dajiang; Ge, Yan; Chen, Yao; Lei, Ting

2018-01-01

Background The aim of this study was to investigate the expression and silencing of the S100A8 gene, which encodes the S100 calcium-binding protein A8 (S100A8), and apoptosis and phosphorylation of protein kinase B (Akt) in tissue samples of endometrial carcinoma and HEC-1A endometrial adenocarcinoma cells in vitro. Material/Methods Immunohistochemistry (IHC) was used to detect expression of the S100A8 protein in 74 tissue samples of endometrial cancer and 22 normal endometrial tissue samples. A stable S100A8 gene knockdown cell line was constructed using lentiviral packing short hairpin RNA (shRNA) transfected into HEC-1A cells. S100A8 mRNA and S100A8 protein levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. The effects of expression of the S100A8 gene by endometrial cancer cells was investigated by the MTT assay, cell cycle and apoptotic assays, qRT-PCR, and Western blotting. Results IHC showed high levels of expression of S100A8 protein in endometrial carcinoma tissues, and HEC-1A adenocarcinoma cells (in G1 and G2). Increased expression of S100A8 protein was found endometrial cancer tissues compared with normal endometrial tissues (79.7% vs. 4.5%). S100A8 gene knockdown reduced cell proliferation in the HEC-1A cells compared with control cells, induced cell apoptosis, inhibited the phosphorylation of protein kinase B (Akt), and induced the expression of pro-apoptotic genes, including the cytochrome C gene, CYCS, BAD, BAX, FOXO1, FOXO3, CASP9, and CASP3. Conclusions In endometrial carcinoma cells, down-regulation of the S100A8 gene induced cell apoptosis via inhibition of the phosphorylated or active form of protein kinase B (Akt). PMID:29595187

Two- and three-dimensional transvaginal ultrasound with power Doppler angiography and gel infusion sonography for diagnosis of endometrial malignancy.

PubMed

Dueholm, M; Christensen, J W; Rydbjerg, S; Hansen, E S; Ørtoft, G

2015-06-01

To evaluate the diagnostic efficiency of two-dimensional (2D) and three-dimensional (3D) transvaginal ultrasonography, power Doppler angiography (PDA) and gel infusion sonography (GIS) at offline analysis for recognition of malignant endometrium compared with real-time evaluation during scanning, and to determine optimal image parameters at 3D analysis. One hundred and sixty-nine consecutive women with postmenopausal bleeding and endometrial thickness ≥ 5 mm underwent systematic evaluation of endometrial pattern on 2D imaging, and 2D videoclips and 3D volumes were later analyzed offline. Histopathological findings at hysteroscopy or hysterectomy were used as the reference standard. The efficiency of the different techniques for diagnosis of malignancy was calculated and compared. 3D image parameters, endometrial volume and 3D vascular indices were assessed. Optimal 3D image parameters were transformed by logistic regression into a risk of endometrial cancer (REC) score, including scores for body mass index, endometrial thickness and endometrial morphology at gray-scale and PDA and GIS. Offline 2D and 3D analysis were equivalent, but had lower diagnostic performance compared with real-time evaluation during scanning. Their diagnostic performance was not markedly improved by the addition of PDA or GIS, but their efficiency was comparable with that of real-time 2D-GIS in offline examinations of good image quality. On logistic regression, the 3D parameters from the REC-score system had the highest diagnostic efficiency. The area under the curve of the REC-score system at 3D-GIS (0.89) was not improved by inclusion of vascular indices or endometrial volume calculations. Real-time evaluation during scanning is most efficient, but offline 2D and 3D analysis is useful for prediction of endometrial cancer when good image quality can be obtained. The diagnostic efficiency at 3D analysis may be improved by use of REC-scoring systems, without the need for calculation of vascular indices or endometrial volume. The optimal imaging modality appears to be real-time 2D-GIS. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Cellular features of endometrial hyperplasia and well differentiated adenocarcinoma using the Endocyte sampler: Diagnostic criteria based on the cytoarchitecture of tissue fragments.

PubMed

Norimatsu, Yoshiaki; Shimizu, Keiko; Kobayashi, Tadao K; Moriya, Takuya; Tsukayama, Choutatsu; Miyake, Yasuyuki; Ohno, Eiji

2006-04-25

Because cellular atypia is often limited in endometrial hyperplasia and well-differentiated endometrial adenocarcinoma (WHO Grade 1 adenocarcinoma), diagnostic criteria for endometrial cytology have not been fully established. New diagnostic criteria based on the composition and architecture of tissue fragments (cytoarchitecture) in the smears were used in the present study. Cytologic features are of less importance because the distinction between endometrial hyperplasia and Grade 1 adenocarcinoma relies more on architectural features than cellular changes. Cell clumps of various size are usually collected abundantly with cytologic material using a disposable scraping device and it was noticed that those cell clumps reflected the histologic architecture. The purpose of the current study was to determine the form of the cytoarchitecture that reflects the histologic structure and to examine the cellular features in endometrial hyperplasia and Grade 1 adenocarcinoma. The frequency of each type of cell clump (tube or sheet-shaped pattern, dilated or branched pattern, irregular protrusion, and papillotubular pattern) were obtained from 49 cases of normal proliferative endometrium (NPE) (patient age range, 28-51 yrs; average age, 39.9 yrs), 63 cases of endometrial hyperplasia without atypia (EH) (patient age range, 35-65 yrs; average age, 47.7 yrs), 13 cases of endometrial hyperplasia with atypia (AEH) (patient age range 47-65 yrs; average age, 53.8 yrs), and 49 cases of Grade 1 adenocarcinoma (patient age range, 42-73 yrs; average age, 58.9 yrs). Certain characteristics of the cytoarchitecture were observed. In the NPE, cell clumps with a tube or sheet-shaped pattern were found in 97.5% of cases. In the EH, cell clumps with a dilated or branched pattern were found in 34.9% of cases. In the Grade 1 adenocarcinoma, cell clumps with irregular protrusions were found in 61.8% cases, whereas a papillotubular pattern was present in 29.7% of cases. The results of the current study revealed that cytoarchitectural criteria appear to be more useful for the cytologic assessment of endometrial lesions, especially for the diagnosis of endometrial hyperplasia and Grade 1 adenocarcinoma. Copyright 2006 American Cancer Society.

Differential Expression and Clinical Significance of DNA Methyltransferase 3B (DNMT3B), Phosphatase and Tensin Homolog (PTEN) and Human MutL Homologs 1 (hMLH1) in Endometrial Carcinomas.

PubMed

Li, Wenting; Wang, Ying; Fang, Xinzhi; Zhou, Mei; Li, Yiqun; Dong, Ying; Wang, Ruozheng

2017-02-21

BACKGROUND The aim of this study was to investigate the expression and the clinicopathologic significance of DNA methyltransferase 3B (DNMT3B), phosphatase and tensin homolog (PTEN) and human MutL homologs 1 (hMLH1) in endometrial carcinomas between Han and Uygur women in Xinjiang. MATERIAL AND METHODS The expression of DNMT3B, PTEN, and hMLH1 in endometrial carcinomas were assessed by immunohistochemistry, followed by an analysis of their relationship to clinical-pathological features and prognosis. RESULTS There were a 61.7% (95/154) overexpression of DNMT3B, 50.0% (77/154) loss of PTEN expression and 18.2% (28/154) loss of hMLH1 expression. The expression of DNMT3B and PTEN in endometrial carcinomas was statistically significantly different between Uygur women and Han women (p=0.001, p=0.010, respectively). DNMT3B expression was statistically significant based on the grade of endometrial carcinomas (p=0.031). PTEN loss was statistically significant between endometrioid carcinomas (ECs) and non endometrioid carcinomas (NECs) (p=0.040). DNMT3B expression was statistically significant in different myometrial invasion groups in Uygur women (p=0.010). Furthermore, the correlation of DNMT3B and PTEN expression was significant in endometrial carcinomas (p=0.021). PTEN expression was statistically significant in the overall survival (OS) rate of women with endometrial cancers (p=0.041). CONCLUSIONS Our findings suggest that PTEN and DNMT3B possess common regulation features as well as certain ethnic differences in expression between Han women and Uygur women. An interaction may exist in the pathogenesis of endometrial carcinoma. DNMT3B was expressed differently in cases of myometrial invasion and PTEN was associated with OS, which suggested that these molecular markers may be useful in the evaluation of the biological behavior of endometrial carcinomas and may be useful indicators of prognosis in women with endometrial carcinomas.

Differential Expression and Clinical Significance of DNA Methyltransferase 3B (DNMT3B), Phosphatase and Tensin Homolog (PTEN) and Human MutL Homologs 1 (hMLH1) in Endometrial Carcinomas

PubMed Central

Li, Wenting; Wang, Ying; Fang, Xinzhi; Zhou, Mei; Li, Yiqun; Dong, Ying; Wang, Ruozheng

2017-01-01

Background The aim of this study was to investigate the expression and the clinicopathologic significance of DNA methyltransferase 3B (DNMT3B), phosphatase and tensin homolog (PTEN) and human MutL homologs 1 (hMLH1) in endometrial carcinomas between Han and Uygur women in Xinjiang. Material/Methods The expression of DNMT3B, PTEN, and hMLH1 in endometrial carcinomas were assessed by immunohistochemistry, followed by an analysis of their relationship to clinical-pathological features and prognosis. Results There were a 61.7% (95/154) overexpression of DNMT3B, 50.0% (77/154) loss of PTEN expression and 18.2% (28/154) loss of hMLH1 expression. The expression of DNMT3B and PTEN in endometrial carcinomas was statistically significantly different between Uygur women and Han women (p=0.001, p=0.010, respectively). DNMT3B expression was statistically significant based on the grade of endometrial carcinomas (p=0.031). PTEN loss was statistically significant between endometrioid carcinomas (ECs) and non endometrioid carcinomas (NECs) (p=0.040). DNMT3B expression was statistically significant in different myometrial invasion groups in Uygur women (p=0.010). Furthermore, the correlation of DNMT3B and PTEN expression was significant in endometrial carcinomas (p=0.021). PTEN expression was statistically significant in the overall survival (OS) rate of women with endometrial cancers (p=0.041). Conclusions Our findings suggest that PTEN and DNMT3B possess common regulation features as well as certain ethnic differences in expression between Han women and Uygur women. An interaction may exist in the pathogenesis of endometrial carcinoma. DNMT3B was expressed differently in cases of myometrial invasion and PTEN was associated with OS, which suggested that these molecular markers may be useful in the evaluation of the biological behavior of endometrial carcinomas and may be useful indicators of prognosis in women with endometrial carcinomas. PMID:28220037

DOE Office of Scientific and Technical Information (OSTI.GOV)

Che, Qi; Liu, Bin-Ya; Wang, Fang-Yuan

Highlights: • IL-6 could promote endometrial cancer cells proliferation. • IL-6 promotes its own production through an autocrine feedback loop. • ERK and NF-κB pathway inhibitors inhibit IL-6 production and tumor growth. • IL-6 secretion relies on the activation of ERK–NF-κB pathway axis. • An orthotopic nude endometrial carcinoma model confirms the effect of IL-6. - Abstract: Interleukin (IL)-6 as an inflammation factor, has been proved to promote cancer proliferation in several human cancers. However, its role in endometrial cancer has not been studied clearly. Previously, we demonstrated that IL-6 promoted endometrial cancer progression through local estrogen biosynthesis. In thismore » study, we proved that IL-6 could directly stimulate endometrial cancer cells proliferation and an autocrine feedback loop increased its production even after the withdrawal of IL-6 from the medium. Next, we analyzed the mechanism underlying IL-6 production in the feedback loop and found that its production and IL-6-stimulated cell proliferation were effectively blocked by pharmacologic inhibitors of nuclear factor-kappa B (NF-κB) and extra-cellular signal-regulated kinase (ERK). Importantly, activation of ERK was upstream of the NF-κB pathways, revealing the hierarchy of this event. Finally, we used an orthotopic nude endometrial carcinoma model to confirm the effects of IL-6 on the tumor progression. Taken together, these data indicate that IL-6 promotes endometrial carcinoma growth through an expanded autocrine regulatory loop and implicate the ERK–NF-κB pathway as a critical mediator of IL-6 production, implying IL-6 to be an important therapeutic target in endometrial carcinoma.« less

Genistein effects on stromal cells determines epithelial proliferation in endometrial co-cultures.

PubMed

Sampey, Brante P; Lewis, Terrence D; Barbier, Claire S; Makowski, Liza; Kaufman, David G

2011-06-01

Estrogen is the leading etiologic factor for endometrial cancer. Estrogen-induced proliferation of endometrial epithelial cells normally requires paracrine growth factors produced by stromal cells. Epidemiologic evidence indicates that dietary soy prevents endometrial cancer, and implicates the phytoestrogen genistein in this effect. However, results from previous studies are conflicting regarding the effects of genistein on hormone responsive cancers. The effects of estrogen and genistein on proliferation of Ishikawa (IK) endometrial adenocarcinoma cells were examined in co-cultures of IK cells with endometrial stromal cells, recapitulating the heterotypic cell-to-cell interactions observed in vivo. The roles of estrogen receptor (ER)α and ERβ were evaluated using ERα and ERβ specific agonists. ER activation and cell proliferation in the IK epithelial cells were determined by alkaline phosphatase assay and Coulter counter enumeration, respectively. Both estrogen and genistein increased estrogen receptor-induced gene activity in IK cells over a range of concentrations. Estrogen alone but not genistein increased IK proliferation in co-cultures. When primed by estrogen treatment, increasing concentrations of genistein produced a biphasic effect on IK proliferation: nM concentrations inhibited estrogen-induced proliferation while μM concentrations increased proliferation. Studies with an ERβ-specific agonist produced similar results. Genistein did not influence the effects of estrogen on IK proliferation in monoculture. Our study indicates that nutritionally relevant concentrations (nM) of genistein inhibit the proliferative effects of estrogen on endometrial adenocarcinoma cells presumably through activation of stromal cell ERβ. We believe that sub-micromolar concentrations of genistein may represent a novel adjuvant for endometrial cancer treatment and prevention. Copyright © 2011 Elsevier Inc. All rights reserved.

Combined colonoscopy and endometrial biopsy cancer screening results in women with Lynch syndrome

PubMed Central

Nebgen, Denise R.; Lu, Karen H.; Rimes, Sue; Keeler, Elizabeth; Broaddus, Russell; Munsell, Mark F.; Lynch, Patrick M.

2015-01-01

Objective Endometrial biopsy (EMBx) and colonoscopy performed under the same sedation is termed combined screening and has been shown to be feasible and to provide a less painful and more satisfactory experience for women with Lynch syndrome (LS). However, clinical results of these screening efforts have not been reported. The purpose of this study was to evaluate the long-term clinical outcomes and patient compliance with serial screenings over the last 10.5 years. Methods We retrospectively analyzed the data for 55 women with LS who underwent combined screening every 1–2 years between 2002 and 2013. Colonoscopy and endometrial biopsy were performed by a gastroenterologist and a gynecologist, with the patient under conscious sedation. Results Out of 111 screening visits in these 55 patients, endometrial biopsies detected one simple hyperplasia, three complex hyperplasia, and one endometrioid adenocarcinoma (FIGO Stage 1A). Seventy one colorectal polyps were removed in 29 patients, of which 29 were tubular adenomas. EMBx in our study detected endometrial cancer in 0.9% (1/111) of surveillance visits, and premalignant hyperplasia in 3.6% (4/111) of screening visits. No interval endometrial or colorectal cancers were detected. Conclusions Combined screening under sedation is feasible and less painful than EMBx alone. Our endometrial pathology detection rates were comparable to yearly screening studies. Our results indicate that screening of asymptomatic LS women with EMBx every 1–2 years, rather than annually, is effective in the early detection of (pre)cancerous lesions, leading to their prompt definitive management, and potential reduction in endometrial cancer. PMID:25149916

Combined colonoscopy and endometrial biopsy cancer screening results in women with Lynch syndrome.

PubMed

Nebgen, Denise R; Lu, Karen H; Rimes, Sue; Keeler, Elizabeth; Broaddus, Russell; Munsell, Mark F; Lynch, Patrick M

2014-10-01

Endometrial biopsy (EMBx) and colonoscopy performed under the same sedation is termed combined screening and has been shown to be feasible and to provide a less painful and more satisfactory experience for women with Lynch syndrome (LS). However, clinical results of these screening efforts have not been reported. The purpose of this study was to evaluate the long-term clinical outcomes and patient compliance with serial screenings over the last 10.5 years. We retrospectively analyzed the data for 55 women with LS who underwent combined screening every 1-2 years between 2002 and 2013. Colonoscopy and endometrial biopsy were performed by a gastroenterologist and a gynecologist, with the patient under conscious sedation. Out of 111 screening visits in these 55 patients, endometrial biopsies detected one simple hyperplasia, three complex hyperplasia, and one endometrioid adenocarcinoma (FIGO Stage 1A). Seventy-one colorectal polyps were removed in 29 patients, of which 29 were tubular adenomas. EMBx in our study detected endometrial cancer in 0.9% (1/111) of surveillance visits, and premalignant hyperplasia in 3.6% (4/111) of screening visits. No interval endometrial or colorectal cancers were detected. Combined screening under sedation is feasible and less painful than EMBx alone. Our endometrial pathology detection rates were comparable to yearly screening studies. Our results indicate that screening of asymptomatic LS women with EMBx every 1-2 years, rather than annually, is effective in the early detection of (pre)cancerous lesions, leading to their prompt definitive management, and potential reduction in endometrial cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

Mechanisms of Normal and Abnormal Endometrial Bleeding

PubMed Central

Lockwood, Charles J.

2011-01-01

Expression of tissue factor (TF), the primary initiator of coagulation, is enhanced in decidualized human endometrial stromal cells (HESC) during the progesterone-dominated luteal phase. Progesterone also augments a second HESC hemostatic factor, plasminogen activator inhibitor-1 (PAI-1). In contrast, progestins inhibit HESC matrix metalloproteinase (MMP)-1, 3 and 9 expression to stabilize endometrial stromal and vascular extracellular matrix. Through these mechanisms decidualized endometrium is rendered both hemostatic and resistant to excess trophoblast invasion in the mid-luteal phase and throughout gestation to prevent hemorrhage and accreta. In non-fertile cycles, progesterone withdrawal results in decreased HESC TF and PAI-expression and increased MMP activity and inflammatory cytokine production promoting the controlled hemorrhage of menstruation and related tissue sloughing. In contrast to these well ordered biochemical processes, unpredictable endometrial bleeding associated with anovulation reflects absence of progestational effects on TF, PAI-1 and MMP activity as well as unrestrained angiogenesis rendering the endometrium non-hemostatic, proteolytic and highly vascular. Abnormal bleeding associated with long-term progestin-only contraceptives results not from impaired hemostasis but from unrestrained angiogenesis leading to large fragile endometrial vessels. This abnormal angiogenesis reflects progestational inhibition of endometrial blood flow promoting local hypoxia and generation of reactive oxygen species that increase production of angiogenic factors such as vascular endothelial growth factor (VEGF) in HESCs and Angiopoietin-2 (Ang-2) in endometrial endothelial cells while decreasing HESC expression of angiostatic, Ang-1. The resulting vessel fragility promotes bleeding. Aberrant angiogenesis also underlies abnormal bleeding associated with myomas and endometrial polyps however there are gaps in our understanding of this pathology. PMID:21499503

Histologic and immunohistochemical analyses of endometrial carcinomas: experiences from endometrial biopsies in 358 consultation cases.

PubMed

Wei, Jian-Jun; Paintal, Ajit; Keh, Pacita

2013-11-01

Uterine serous carcinoma is biologically more aggressive than the endometrioid carcinoma. Because uterine serous carcinoma has a high propensity for lymphovascular invasion and intraperitoneal and extra-abdominal spread, accurate diagnosis of this tumor type in endometrial biopsies/curettings is critical for appropriate clinical management. To share our experience in the evaluation of endometrial biopsy specimens in type I and type II endometrial adenocarcinoma. We retrospectively reviewed 358 biopsies containing endometrial carcinoma during a recent 3 year period of our consultation records. In cases in which our interpretation differed from the submitting diagnosis, a panel of immunostains was performed. The performance characteristics of each antibody in our panel was calculated in this group of challenging cases. Among the endometrial carcinomas we examined, a diagnosis of type I carcinoma accounted for 91% of cases (327 of 358) and type II carcinoma for 9% of cases (31 of 358); 41 cases (11.5%) were ambiguous or discordant (differing from submitted diagnoses and reviewed) based on histology alone. All 41 ambiguous and discordant cases were further evaluated with a battery of immunohistochemical markers. Of the 41 cases, 36 (88%) were ultimately classified (10 cases [24%] were endometrioid carcinoma; 18 cases [44%] were uterine serous carcinoma; 8 cases [20%] resulted in various other outcomes) and 5 cases (12%) remained indeterminate. Making the distinction between type I and II endometrial carcinoma remains a common problem in general practice. Although no one biomarker provides excellent statistical performance, a panel of immunohistochemical markers is often useful in difficult cases.

The frequency and significance of WT-1 expression in serous endometrial carcinoma.

PubMed

Hedley, Catherine; Sriraksa, Ruethairat; Showeil, Rania; Van Noorden, Susan; El-Bahrawy, Mona

2014-09-01

Serous endometrial carcinoma is an aggressive type of endometrial carcinoma. Wilms tumor gene 1 (WT-1) is commonly expressed in ovarian serous carcinomas and considered a diagnostic marker of these tumors. However, it is generally believed that WT-1 is rarely expressed by endometrial serous carcinoma. The aim of this study was to evaluate the frequency and significance of WT-1 expression in endometrial serous carcinoma. We studied the expression of WT-1 in formalin-fixed, paraffin-embedded tumor sections from 77 cases of endometrial serous carcinoma. Thirty-four tumors showed positive expression for WT-1 (44%). There was a statistically significant association between the presence of WT-1 expression and disease-free survival (DFS), where patients with tumors expressing WT-1 had a shorter DFS compared with those with no WT-1 expression (P = .031; median DFS, 15 and 38 months, respectively). By multivariate Cox regression analysis, DFS was independent from other clinicopathological data (tumor stage, presence of lymphovascular space invasion, cervical involvement, and extrauterine spread), indicating that WT-1 expression is independently associated with DFS. Our study shows that WT-1 is expressed in a considerable percentage of endometrial serous carcinomas, suggesting a role for WT-1 in the pathology of these tumors. This has therapeutic significance, as WT-1 is an emerging target for immunotherapy. Moreover, our results show that WT-1 has prognostic value, being predictive of DFS. As a potential prognostic marker and therapeutic target, we recommend that WT-1 expression should be included in histopathologic reports of endometrial serous carcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

[Aromatase activities of endometrial carcinomas and both basic and clinical analyses of endometrial hyperplasia as a premalignant disease].

PubMed

Sasaki, H

1993-08-01

Paraffin-embedded materials obtained from 117 cases of endometrial hyperplasia and 84 cases of carcinoma were used for measurement of both ki-ras and p53 gene mutation and aromatase (ARO) and TGF-alpha immunostaining. The overall incidence of ki-ras mutations in the hyperplasia specimens (16%) was similar to the incidence detected in carcinomas (18%). None of 117 endometrial hyperplasias were found to have mutations in the p53 gene, whereas mutations were seen in 3 (13.3%) endometrial carcinomas. The intensity of both ARO and TGF-alpha immunostaining was increased in glands of both hyperplasia and carcinoma, and also in the interstitium of carcinoma. The positive sites of both ARO and TGF-alpha were almost the same, with an incidence below 40% in both hyperplasias and carcinomas. The cultured cells of endometrial carcinoma showed aromatase activity below MCF-7 cells, because testosterone was converted to estradiol (E2). TGF-alpha induced cell growth with at an optimal concentration. In HEC-59 cells, TGF-alpha increased both ARO-activity and mRNA. Some promoters on ARO-exon 1 in HEC-59 cells were different from those in BeWo cells. Progesterone inhibited the E2-induced excretion of pre TGF-alpha in endometrial carcinoma cells. These findings suggest that endometrial hyperplasia can be a premalignant condition of carcinoma, and can be initiated by both ki-ras codon 12 mutation and abnormal activity of ARO induced by TGF-alpha. In addition, HEC-59 cells may possess autocrine/paracrine properties involving ARO, E2 and TGF-alpha.

Hypoxia and prostaglandin E receptor 4 signalling pathways synergise to promote endometrial adenocarcinoma cell proliferation and tumour growth.

PubMed

Catalano, Rob D; Wilson, Martin R; Boddy, Sheila C; McKinlay, Andrew T M; Sales, Kurt J; Jabbour, Henry N

2011-05-12

The prostaglandin endoperoxide synthase (PTGS) pathway is a potent driver of tumour development in humans by enhancing the biosynthesis and signalling of prostaglandin (PG) E(2). PTGS2 expression and PGE(2) biosynthesis is elevated in endometrial adenocarcinoma, however the mechanism whereby PTGS and PGE(2) regulate endometrial tumour growth is unknown. Here we investigated (a) the expression profile of the PGE synthase enzymes (PTGES, PTGES-2, PTGES-3) and PGE receptors (PTGER1-4) in endometrial adenocarcinomas compared with normal endometrium and (b) the role of PTGER4 in endometrial tumorigenesis in vivo. We found elevated expression of PTGES2 and PTGER4 and suppression of PTGER1 and PTGER3 in endometrial adenocarcinomas compared with normal endometrium. Using WT Ishikawa endometrial adenocarcinoma cells and Ishikawa cells stably transfected with the full length PTGER4 cDNA (PTGER4 cells) xenografted in the dorsal flanks of nude mice, we show that PTGER4 rapidly and significantly enhances tumour growth rate. Coincident with enhanced PTGER4-mediated tumour growth we found elevated expression of PTGS2 in PTGER4 xenografts compared with WT xenografts. Furthermore we found that the augmented growth rate of the PTGER4 xenografts was not due to enhanced angiogenesis, but regulated by an increased proliferation index and hypoxia. In vitro, we found that PGE(2) and hypoxia independently induce expression of PTGER4 indicating two independent pathways regulating prostanoid receptor expression. Finally we have shown that PGE(2) and hypoxia synergise to promote cellular proliferation of endometrial adenocarcinoma cells.

Hypoxia and Prostaglandin E Receptor 4 Signalling Pathways Synergise to Promote Endometrial Adenocarcinoma Cell Proliferation and Tumour Growth

PubMed Central

Catalano, Rob D.; Wilson, Martin R.; Boddy, Sheila C.; McKinlay, Andrew T. M.; Sales, Kurt J.; Jabbour, Henry N.

2011-01-01

The prostaglandin endoperoxide synthase (PTGS) pathway is a potent driver of tumour development in humans by enhancing the biosynthesis and signalling of prostaglandin (PG) E2. PTGS2 expression and PGE2 biosynthesis is elevated in endometrial adenocarcinoma, however the mechanism whereby PTGS and PGE2 regulate endometrial tumour growth is unknown. Here we investigated (a) the expression profile of the PGE synthase enzymes (PTGES, PTGES-2, PTGES-3) and PGE receptors (PTGER1–4) in endometrial adenocarcinomas compared with normal endometrium and (b) the role of PTGER4 in endometrial tumorigenesis in vivo. We found elevated expression of PTGES2 and PTGER4 and suppression of PTGER1 and PTGER3 in endometrial adenocarcinomas compared with normal endometrium. Using WT Ishikawa endometrial adenocarcinoma cells and Ishikawa cells stably transfected with the full length PTGER4 cDNA (PTGER4 cells) xenografted in the dorsal flanks of nude mice, we show that PTGER4 rapidly and significantly enhances tumour growth rate. Coincident with enhanced PTGER4-mediated tumour growth we found elevated expression of PTGS2 in PTGER4 xenografts compared with WT xenografts. Furthermore we found that the augmented growth rate of the PTGER4 xenografts was not due to enhanced angiogenesis, but regulated by an increased proliferation index and hypoxia. In vitro, we found that PGE2 and hypoxia independently induce expression of PTGER4 indicating two independent pathways regulating prostanoid receptor expression. Finally we have shown that PGE2 and hypoxia synergise to promote cellular proliferation of endometrial adenocarcinoma cells. PMID:21589857

Histopathological pattern of abnormal uterine bleeding in endometrial biopsies.

PubMed

Vaidya, S; Lakhey, M; Vaidya, S; Sharma, P K; Hirachand, S; Lama, S; KC, S

2013-03-01

Abnormal uterine bleeding is a common presenting complaint in gyanecology out patient department. Histopathological evaluation of the endometrial samples plays a significant role in the diagnosis of abnormal uterine bleeding. This study was carried out to determine the histopathological pattern of the endometrium in women of various age groups presenting with abnormal uterine bleeding. Endometrial biopsies and curettings of patients presenting with abnormal uterine bleeding was retrospectively studied. A total of 403 endometrial biopsies and curettings were analyzed. The age of the patients ranged from 18 to 70 years. Normal cyclical endometrium was seen in 165 (40.94%) cases, followed by 54 (13.40%) cases of disordered proliferative endometrium and 44 (10.92%) cases of hyperplasia. Malignancy was seen in 10 (2.48%) cases. Hyperplasia and malignancy were more common in the perimenopausal and postmenopausal age groups. Histopathological examination of endometrial biopsies and curettings in patients presenting with abnormal uterine bleeding showed a wide spectrum of changes ranging from normal endometrium to malignancy. Endometrial evaluation is specially recommended in women of perimenopausal and postmenopausal age groups presenting with AUB, to rule out a possibility of any preneoplastic condition or malignancy.

George Papanicolaou's Efforts to Develop Novel Cytologic Methods for the Early Diagnosis of Endometrial Carcinoma.

PubMed

Austin, R Marshall

2017-01-01

Toward the end of his career, Dr. George Papanicolaou became interested in human endometrial explants placed into tissue culture. The initial focus of his studies was on phagocytic cells emanating from endometrial explants and their role in cleansing the uterine cavity after each menstrual cycle and in sterilizing the uterine cavity in the face of infection. Papanicolaou also observed that growth rates of explanted normal and pathologic endometrial tissues differed considerably. Explants of endometrial malignancies exhibited not only increased growth rates but also visible proliferation of cells with readily identifiable cytologic features of malignancy. Acknowledging that cytologic screening for early diagnosis of intrauterine malignancies had up to that point not proven to be reliable as screening for cervical cancer, he hoped that the tissue culture explant technique could prove to be a new adjunctive diagnostic method for the diagnosis of endometrial and other female genital tract malignancies not readily detectible by other diagnostic procedures. Papanicolaou's untimely death in 1962 cut short his progress in this area of study. © 2017 S. Karger AG, Basel.

Tamoxifen has a proliferative effect in endometrial carcinoma mediated via the GPER/EGFR/ERK/cyclin D1 pathway: A retrospective study and an in vitro study.

PubMed

Zhang, Lizhi; Li, Yanmin; Lan, Lan; Liu, Rong; Wu, Yanhong; Qu, Quanxin; Wen, Ke

2016-12-05

Tamoxifen has been widely used to treat breast cancer as an endocrine therapy. However, tamoxifen is known to enhance the risk of developing endometrial cancer. We want to examine the effect of tamoxifen on endometrial cancer. In our retrospective study, we found that high grade, high stage, and lymph node metastasis were more common in tamoxifen users. In vitro 4-hydroxytamoxifen (OHT) induced cell proliferation and cell cycle promotion in type I and type II endometrial cancer cell lines, and this proliferation was blocked by GPER silencing. Treatment with OHT increased EGFR and ERK phosphorylation and the mRNA and protein levels of cyclin D1 and GPER. Taken together, our data demonstrate that endometrial cancer patients with tamoxifen treatment exhibit more aggressive histological subtypes and worse prognosis. OHT is a proliferation-inducing agent for endometrial cancer cells, and the GPER/EFGR/ERK/cyclin D1 pathway is involved in this process. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Does Bariatric Surgery Affect the Incidence of Endometrial Cancer Development? A Systematic Review.

PubMed

Winder, Alec A; Kularatna, Malsha; MacCormick, Andrew D

2018-05-01

Obesity has been linked to an increased prevalence in multiple cancers. Studies have suggested a reduction in the overall risk of cancer after bariatric surgery. We reviewed the evidence for bariatric surgery reducing the risk of endometrial cancer. Data was extracted from PubMed, EMBASE, and Medline to perform a systematic review. Thirty-one full text articles were identified from 265 abstracts. Nine observational studies were relevant to endometrial cancer. In the five controlled studies, 462 of 113,032 (0.4%) patients receiving bariatric surgery versus 11,997 of 848,864 (1.4%) controls developed endometrial cancer, odds ratio of 0.317 (95% CI 0.161 to 0.627) using random effects model (P < 0.001). Bariatric surgery seems to reduce the risk of endometrial cancer; however, more research is required.

Application of Immunohistochemistry and Molecular Diagnostics to Clinically Relevant Problems in Endometrial Cancer Bojana Djordjevic, Shannon Westin, Russell R. Broaddus

PubMed Central

Djordjevic, Bojana; Westin, Shannon; Broaddus, Russell R.

2012-01-01

Synopsis A number of different clinical scenarios are presented in which lab-based analyses beyond the usual diagnosis based on light microscopic examination of H&E stained slides – immunohistochemistry and PCR-based assays such as sequencing, mutation testing, microsatellite instability analysis, and determination of MLH1 methylation - are most helpful for guiding diagnosis and treatment of endometrial cancer. The central goal of this information is to provide a practical guide of key current and emerging issues in diagnostic endometrial cancer pathology that require the use of ancillary laboratory techniques, such as immunohistochemistry and molecular testing. The authors present the common diagnostic problems in endometrial carcinoma pathology, types of endometrial carcinoma, description of tissue testing and markers, pathological features, and targeted therapy. PMID:23687522

Endometrial Receptivity and its Predictive Value for IVF/ICSI-Outcome

PubMed Central

Heger, A.; Sator, M.; Pietrowski, D.

2012-01-01

Endometrial receptivity plays a crucial role in the establishment of a healthy pregnancy in cycles of assisted reproduction. The endometrium as a key factor during reproduction can be assessed in multiple ways, most commonly through transvaginal grey-scale or 3-D ultrasound. It has been shown that controlled ovarian hyperstimulation has a great impact on the uterine lining, which leads to different study results for the predictive value of endometrial factors measured on different cycle days. There is no clear consensus on whether endometrial factors are appropriate to predict treatment outcome and if so, which one is suited best. The aim of this review is to summarize recent findings of studies about the influence of endometrial thickness, volume and pattern on IVF- and ICSI-treatment outcome and provide an overview of future developments in the field. PMID:25258462

Endometrial Receptivity and its Predictive Value for IVF/ICSI-Outcome.

PubMed

Heger, A; Sator, M; Pietrowski, D

2012-08-01

Endometrial receptivity plays a crucial role in the establishment of a healthy pregnancy in cycles of assisted reproduction. The endometrium as a key factor during reproduction can be assessed in multiple ways, most commonly through transvaginal grey-scale or 3-D ultrasound. It has been shown that controlled ovarian hyperstimulation has a great impact on the uterine lining, which leads to different study results for the predictive value of endometrial factors measured on different cycle days. There is no clear consensus on whether endometrial factors are appropriate to predict treatment outcome and if so, which one is suited best. The aim of this review is to summarize recent findings of studies about the influence of endometrial thickness, volume and pattern on IVF- and ICSI-treatment outcome and provide an overview of future developments in the field.

Project for the National Program of Early Diagnosis of Endometrial Cancer Part I.

PubMed

Bohîlțea, R E; Ancăr, V; Cirstoiu, M M; Rădoi, V; Bohîlțea, L C; Furtunescu, F

2015-01-01

Endometrial cancer recorded a peak incidence in ages 60-64 years in Romania, reaching in 2013 the average value of 8.06/ 100,000 women, and 15.97/ 100,000 women within the highest risk age range, having in recent years an increasing trend, being higher in urban than in rural population. Annually, approximately 800 new cases are registered in our country. The estimated lifetime risk of a woman to develop endometrial cancer is of about 1,03%. Based on an abnormal uterine bleeding, 35% of the endometrial cancers are diagnosed in an advanced stage of the disease, with significantly diminished lifetime expectancy. Drafting a national program for the early diagnosis of endometrial cancer. We proposed a standardization of the diagnostic steps and focused on 4 key elements for the early diagnosis of endometrial cancer: investigation of abnormal uterine bleeding occurring in pre/ post-menopausal women, investigating features/ anomalies of cervical cytology examination, diagnosis, treatment and proper monitoring of precursor endometrial lesions or cancer associated endometrial lesions and screening high risk populations (Lynch syndrome, Cowden syndrome). Improving medical practice based on diagnostic algorithms addresses the four risk groups, by improving information system reporting and record keeping. Improving addressability cases by increasing the health education of the population will increase the rate of diagnosis of endometrial cancer in the early stages of the disease. ACOG = American Society of Obstetricians and Gynecologists, ASCCP = American Society for Colposcopy and Cervical Pathology, PATT = Partial Activated Thromboplastin Time, BRCA = Breast Cancer Gene, CT = Computerized Tomography, IFGO = International Federation of Gynecology and Obstetrics, HLG = Hemoleucogram, HNPCC = Hereditary Nonpolyposis Colorectal Cancer (Lynch syndrome), IHC = Immunohistochemistry, BMI = Body Mass Index, INR = International Normalized Ratio, MSI = Microsatellites instability, MSI-H/ MSI-L = high (positive test)/ low (negative test) microsatellites instability, WHO = World Health Organization, PCR = Polymerase chain reaction, MRI = Magnetic Resonance Imaging, SGO = Society of Gynecologic Oncologists, SHG = Sonohysterography, SRU = Society of Radiologists in Ultrasound, TQ = Time Quick, BT = Bleeding Time, TVUS = Transvaginal ultrasound, USPIO = Ultrasmall superparamagnetic iron oxide.

Re-establishment of gap junctional intercellular communication (GJIC) between human endometrial carcinomas by prostaglandin E(2).

PubMed

Schlemmer, Scott R; Kaufman, David G

2012-12-01

Reduced intercellular communication via gap junctions is correlated with carcinogenesis. Gap junctional intercellular communication (GJIC), between normal human endometrial epithelial cells is enhanced when endometrial stromal cells were present in culture. This enhancement of GJIC between normal epithelial cells also occurs when they are cultured in medium conditioned by stromal cells. This observation indicated that a soluble compound (or compounds) produced and secreted by stromal cells mediates GJIC in epithelial cells. Previous studies have shown that endometrial stromal cells release prostaglandin E(2) (PGE(2)) and prostaglandin F(2α) (PGF(2α)) under physiological conditions. When we evaluated the response of normal endometrial epithelial cells to various concentrations of PGE(2,) we found enhanced GJIC with 1nM PGE(2). This is a smaller increase in GJIC than that induced by medium conditioned by stromal cells. When the extracellular concentration of PGE(2) was measured after incubation with stromal cells, it was found to be similar to the concentrations showing maximal GJIC between the normal epithelial cells. When indomethacin was used to inhibit prostaglandin synthesis by stromal cells, GJIC was reduced but not eliminated between normal endometrial epithelial cells. These observations suggest that although PGE(2) secreted by stromal cells is an important mediator of GJIC between the epithelial cells, it is not the sole mediator. Transformed endometrial epithelial cells did not demonstrate GJIC even in the presence of stromal cells. However, we were able to re-establish GJIC in transformed epithelial cells when we added PGE(2) to the cells. Our findings show that PGE(2) may serve as an intercellular mediator between stromal and epithelial cells that regulates GJIC in normal and malignant epithelial cells. This suggests that maintenance of GJIC by preserving or replacing PGE(2) secretion by endometrial stromal cells may have the potential to suppress carcinogenesis in endometrial epithelial cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Oral isoflavone supplementation on endometrial thickness: a meta-analysis of randomized placebo-controlled trials

PubMed Central

Liu, Jie; Yuan, Feixiang; Gao, Jian; Shan, Boer; Ren, Yulan; Wang, Huaying; Gao, Ying

2016-01-01

Background Isoflavone from soy and other plants modulate hormonal effects in women, and the hormone disorder might result in different caners including endometrial cancer. However, it's effect on the risk of endometrial cancer is still inconclusive. We aimed to assess the effects of isoflavone on endometrial thickness, a risk factor of endometrial cancer in peri- and post-menopausal women. Methods A meta-analysis of randomized controlled trials was conducted to evaluate the effect of oral isoflavone supplementation on endometrial thickness in peri- and post-menopausal women. Electronic searches were performed on the PubMed, Embase, the Cochrane Library, web of science, CINAHL, and WHO ICTRP to August 1st, 2015. Reviews and reference lists of relevant articles were also searched to identify more studies. Summary estimates of standard mean differences (SMD's) and 95%CIs were obtained with random-effects models. Heterogeneity was evaluated with meta-regression and stratified analyses. Results A total of 23 trials were included in the current analysis. The overall results did not show significant change of endometrial thickness after oral isoflavone supplementation (23 studies, 2167subjects; SMD:-0.05; 95%CI:-0.23, 0.13; P=0.60). Stratified analysis suggested that a daily dose of more than 54mg could decrease the endometrial thickness for 0.26mm (10 trials, 984subjects; SMD:-0.26; 95%CI:-0.45, −0.07; P=0.007). Furthermore, isoflavone supplementation significantly decrease the endometrial thickness for 0.23mm in North American studies (7 trials, 726 subjects; SMD:-0.23; 95%CI:-0.44, −0.01; P=0.04), but it suggested an increase for 0.23mm in Asian studies (3 trials, 224 subjects; SMD: 0.23; 95%CI:-0.04, 0.50; P=0.10). Conclusion Oral isoflavone supplementation might have different effects in different populations and at different daily doses. Multiple-centre, larger, and long-term trials are deserved to further evaluate its effect. PMID:26967050

Estrogenic G protein-coupled receptor 30 signaling is involved in regulation of endometrial carcinoma by promoting proliferation, invasion potential, and interleukin-6 secretion via the MEK/ERK mitogen-activated protein kinase pathway.

PubMed

He, Yin-Yan; Cai, Bin; Yang, Yi-Xia; Liu, Xue-Lian; Wan, Xiao-Ping

2009-06-01

The regulatory mechanism of endometrial carcinoma and the signal transduction pathways involved in hormone action are poorly defined. It has become apparent that the G protein-coupled receptor (GPR) 30 mediates the non-genomic signaling of 17beta-estradiol (E2). Here we show that GPR30 is highly expressed in endometrial cancer tissues and cancer cell lines and positively regulates cell proliferation and invasion. GPR30 expression was detected in 50 human endometrial carcinomas. The transcription level of GPR30 was significantly higher in the tissue of endometrial carcinoma than in normal endometrium (P < 0.05). Immunohistochemical assays revealed that the positive expression rate of GPR30 protein in endometrial carcinoma tissue (35/50, 70%) was statistically higher than in normal endometrium tissue (8/30, 26.67%) (chi2 = 14.16, P = 0.0002). GPR30 overexpression was correlated with high-grade endometrial carcinoma. GPR30 expression was also found in two human endometrial cancer cell lines: RL95-2 (estrogen receptor positive) and KLE (estrogen receptor negative). The roles of GPR30 in proliferative and invasive responses to E2 and G1, a non-steroidal GPR30-specific agonist, in RL95-2 and KLE cell lines were then explored. We showed that E2 and G1 could initiate the MAPK/ERK mitogen-activated protein kinase pathway in both cell lines. What's more, E2 and G1 promoted KLE and RL95-2 proliferation and stimulated matrix metalloproteinase production and activity via the GPR30-mediated MEK/ERK mitogen-activated protein kinase pathway, as well as increased interleukin-6 secretion. These findings suggest that GPR30-mediated non-genomic signaling could play an important role in endometrial cancer.

Premenopausal abnormal uterine bleeding and risk of endometrial cancer.

PubMed

Pennant, M E; Mehta, R; Moody, P; Hackett, G; Prentice, A; Sharp, S J; Lakshman, R

2017-02-01

Endometrial biopsies are undertaken in premenopausal women with abnormal uterine bleeding but the risk of endometrial cancer or atypical hyperplasia is unclear. To conduct a systematic literature review to establish the risk of endometrial cancer and atypical hyperplasia in premenopausal women with abnormal uterine bleeding. Search of PubMed, Embase and the Cochrane Library from database inception to August 2015. Studies reporting rates of endometrial cancer and/or atypical hyperplasia in women with premenopausal abnormal uterine bleeding. Data were independently extracted by two reviewers and cross-checked. For each outcome, the risk and a 95% CI were estimated using logistic regression with robust standard errors to account for clustering by study. Sixty-five articles contributed to the analysis. Risk of endometrial cancer was 0.33% (95% CI 0.23-0.48%, n = 29 059; 97 cases) and risk of endometrial cancer or atypical hyperplasia was 1.31% (95% CI 0.96-1.80, n = 15 772; 207 cases). Risk of endometrial cancer was lower in women with heavy menstrual bleeding (HMB) (0.11%, 95% CI 0.04-0.32%, n = 8352; 9 cases) compared with inter-menstrual bleeding (IMB) (0.52%, 95% CI 0.23-1.16%, n = 3109; 14 cases). Of five studies reporting the rate of atypical hyperplasia in women with HMB, none identified any cases. The risk of endometrial cancer or atypical hyperplasia in premenopausal women with abnormal uterine bleeding is low. Premenopausal women with abnormal uterine bleeding should first undergo conventional medical management. Where this fails, the presence of IMB and older age may be indicators for further investigation. Further research into the risks associated with age and the cumulative risk of co-morbidities is needed. Contrary to practice, premenopausal women with heavy periods or inter-menstrual bleeding rarely require biopsy. © 2016 The Authors BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

Soy Isoflavones for Reducing Bone Loss (SIRBL) Study: Effect of a three-year trial on hormones, adverse events, and endometrial thickness in postmenopausal women

PubMed Central

Alekel, D. Lee; Genschel, Ulrike; Koehler, Kenneth J; Hofmann, Heike; Van Loan, Marta D; Beer, Bonnie S.; Hanson, Laura N; Peterson, Charles T; Kurzer, Mindy S

2014-01-01

Objectives To assess the overall safety and potential endometrial stimulation of soy isoflavone tablets consumed (3-year) by postmenopausal women. To determine the endometrial thickness response-to-treatment among compliant women, taking into account hormone concentrations and other hypothesized modifying factors. Methods We randomized healthy postmenopausal women (45.8–65.0 years) to placebo control or two doses (80 or 120 mg/day) of soy isoflavones at two sites. We used intent-to-treat (N=224) and compliant (>95%; N=208) analyses to assess circulating hormone concentrations, adverse events, and endometrial thickness (via transvaginal ultrasound). Results Median values for endometrial thickness (mm) declined from baseline through 36 mo. Nonparametric ANOVA for treatment differences among groups showed no differences in absolute (or percentage change) endometrial thickness at any time point (Chi-Square p-values ranged from 0.12–0.69), nor in circulating hormones at any time point. A greater number of adverse events for the genitourinary system (p=0.005) was noted in the 80 compared to 120 mg/day group, whereas other systems showed no treatment effects. The model predicting the endometrial thickness response-(using natural logarithm)-to-treatment with compliant women across time points was significant (p<0.0001), indicating that estrogen exposure (p=0.0013), plasma 17 β-estradiol (p=0.0086), and alcohol intake (p=0.023) contributed significantly to the response. Neither the 80 (p=0.57) nor 120 (p=0.43) mg/day dose exerted an effect on endometrial thickness across time. Conclusions Our RCT verified the long-term overall safety of consuming soy isoflavone tablets by postmenopausal women who displayed excellent compliance. We found no evidence of a treatment effect on endometrial thickness, adverse events, or circulating hormone concentrations, most notably thyroid function, during a three year period. PMID:25003624

Inverse Relationship between Progesterone Receptor and Myc in Endometrial Cancer

PubMed Central

Dai, Donghai; Meng, Xiangbing; Thiel, Kristina W.; Leslie, Kimberly K.; Yang, Shujie

2016-01-01

Endometrial cancer, the most common gynecologic malignancy, is a hormonally-regulated disease. Response to progestin therapy positively correlates with hormone receptor expression, in particular progesterone receptor (PR). However, many advanced tumors lose PR expression. We recently reported that the efficacy of progestin therapy can be significantly enhanced by combining progestin with epigenetic modulators, which we term “molecularly enhanced progestin therapy.” What remained unclear was the mechanism of action and if estrogen receptor α (ERα), the principle inducer of PR, is necessary to restore functional expression of PR via molecularly enhanced progestin therapy. Therefore, we modeled advanced endometrial tumors that have lost both ERα and PR expression by generating ERα-null endometrial cancer cell lines. CRISPR-Cas9 technology was used to delete ERα at the genomic level. Our data demonstrate that treatment with a histone deacetylase inhibitor (HDACi) was sufficient to restore functional PR expression, even in cells devoid of ERα. Our studies also revealed that HDACi treatment results in marked downregulation of the oncogene Myc. We established that PR is a negative transcriptional regulator of Myc in endometrial cancer in the presence or absence of ERα, which is in contrast to studies in breast cancer cells. First, estrogen stimulation augmented PR expression and decreased Myc in endometrial cancer cell lines. Second, progesterone increased PR activity yet blunted Myc mRNA and protein expression. Finally, overexpression of PR by adenoviral transduction in ERα-null endometrial cancer cells significantly decreased expression of Myc and Myc-regulated genes. Analysis of the Cancer Genome Atlas (TCGA) database of endometrial tumors identified an inverse correlation between PR and Myc mRNA levels, with a corresponding inverse correlation between PR and Myc downstream transcriptional targets SRD5A1, CDK2 and CCNB1. Together, these data reveal a previously unanticipated inverse relationship between the tumor suppressor PR and the oncogene Myc in endometrial cancer. PMID:26859414

Molecular alterations in endometrial and ovarian clear cell carcinomas: clinical impacts of telomerase reverse transcriptase promoter mutation.

PubMed

Huang, Hsien-Neng; Chiang, Ying-Cheng; Cheng, Wen-Fang; Chen, Chi-An; Lin, Ming-Chieh; Kuo, Kuan-Ting

2015-02-01

Recently, mutations of telomerase reverse transcriptase (TERT) promoter were found in several types of cancer. A few reports demonstrate TERT promoter mutations in ovarian clear cell carcinomas but endometrial clear cell carcinoma has not been studied. The aims of this study were to compare differences of molecular alterations and clinical factors, and identify their prognostic impact in endometrial and ovarian clear cell carcinomas. We evaluated mutations of the TERT promoter and PIK3CA, expression of ARID1A, and other clinicopathological factors in 56 ovarian and 14 endometrial clear cell carcinomas. We found that TERT promoter mutations were present in 21% (3/14) of endometrial clear cell carcinomas and 16% (9/56) of ovarian clear cell carcinomas. Compared with ovarian clear cell carcinomas, endometrial clear cell carcinomas showed older mean patient age (P<0.001), preserved ARID1A immunoreactivity (P=0.017) and infrequent PIK3CA mutation (P=0.025). In ovarian clear cell carcinomas, TERT promoter mutations were correlated with patient age >45 (P=0.045) and preserved ARID1A expression (P=0.003). In cases of endometrial clear cell carcinoma, TERT promoter mutations were not statistically associated with any other clinicopathological factors. In ovarian clear cell carcinoma patients with early FIGO stage (stages I and II), TERT promoter mutation was an independent prognostic factor and correlated with a shorter disease-free survival and overall survival (P=0.015 and 0.009, respectively). In recurrent ovarian clear cell carcinoma patients with early FIGO stage, TERT promoter mutations were associated with early relapse within 6 months (P=0.018). We concluded that TERT promoter mutations were present in endometrial and ovarian clear cell carcinomas. Distinct molecular alteration patterns in endometrial and ovarian clear cell carcinomas implied different processes of tumorigenesis in these morphologically similar tumors. In ovarian clear cell carcinoma of early FIGO stage, patients with TERT promoter mutation require close follow-up during the initial 6 months following chemotherapy.

Inhibitory effect of 2-(piperidinoethoxyphenyl)-3-(4-hydroxyphenyl)-2H-benzo(b)pyran (K-1) on human primary endometrial hyperplasial cells mediated via combined suppression of Wnt/β-catenin signaling and PI3K/Akt survival pathway.

PubMed

Chandra, V; Fatima, I; Manohar, M; Popli, P; Sirohi, V K; Hussain, M K; Hajela, K; Sankhwar, P; Dwivedi, A

2014-08-21

Endometrial hyperplasia is a precursor to the most common gynecologic cancer diagnosed in women. Apart from estrogenic induction, aberrant activation of the Wnt/β-catenin signal is well known to correlate with endometrial hyperplasia and its carcinoma. The benzopyran compound 2-(piperidinoethoxyphenyl)-3-(4-hydroxyphenyl)-2H-benzo (b) pyran(K-1), a potent antiestrogenic agent, has been shown to have apoptosis-inducing activity in rat uterine hyperplasia. The current study was undertaken to explore the effect of the benzopyran compound K-1 on growth and Wnt signaling in human endometrial hyperplasial cells. Primary culture of atypical endometrial hyperplasial cells was characterized by the epithelial cell marker cytokeratin-7. Results revealed that compound K-1 reduced the viability of primary endometrial hyperplasial cells and expression of ERα, PR, PCNA, Wnt7a, FZD6, pGsk3β and β-catenin without affecting the growth of the primary culture of normal endometrial cells. The β-catenin target genes CyclinD1 and c-myc were also found to be reduced, whereas the expression of axin2 and Wnt/β-catenin signaling inhibitor Dkk-1 was found to be upregulated, which caused the reduced interaction of Wnt7a and FZD6. Nuclear accumulation of β-catenin was found to be decreased by compound K-1. K-1 also suppressed the pPI3K/pAkt survival pathway and induced the cleavage of caspases and PARP, thus subsequently causing the apoptosis of endometrial hyperplasial cells. In conclusion, compound K-1 suppressed the growth of human primary endometrial hyperplasial cells through discontinued Wnt/β-catenin signaling and induced apoptosis via inhibiting the PI3K/Akt survival pathway.

Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women’s Health Initiative Randomized Trial

PubMed Central

Anderson, G. L.; Sarto, G. E.; Haque, R.; Runowicz, C. D.; Aragaki, A. K.; Thomson, C. A.; Howard, B. V.; Wactawski-Wende, J.; Chen, C.; Rohan, T. E.; Simon, M. S.; Reed, S. D.; Manson, J. E.

2016-01-01

Background: While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women’s Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. Methods: The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided. Results: After 5.6 years’ median intervention and 13 years’ median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). Conclusion: In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence. PMID:26668177

Age at Last Birth in Relation to Risk of Endometrial Cancer: Pooled Analysis in the Epidemiology of Endometrial Cancer Consortium

PubMed Central

Setiawan, Veronica Wendy; Pike, Malcolm C.; Karageorgi, Stalo; Deming, Sandra L.; Anderson, Kristin; Bernstein, Leslie; Brinton, Louise A.; Cai, Hui; Cerhan, James R.; Cozen, Wendy; Chen, Chu; Doherty, Jennifer; Freudenheim, Jo L.; Goodman, Marc T.; Hankinson, Susan E.; Lacey, James V.; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Lurie, Galina; Mack, Thomas; Matsuno, Rayna K.; McCann, Susan; Moysich, Kirsten B.; Olson, Sara H.; Rastogi, Radhai; Rebbeck, Timothy R.; Risch, Harvey; Robien, Kim; Schairer, Catherine; Shu, Xiao-Ou; Spurdle, Amanda B.; Strom, Brian L.; Thompson, Pamela J.; Ursin, Giske; Webb, Penelope M.; Weiss, Noel S.; Wentzensen, Nicolas; Xiang, Yong-Bing; Yang, Hannah P.; Yu, Herbert; Horn-Ross, Pamela L.; De Vivo, Immaculata

2012-01-01

Childbearing at an older age has been associated with a lower risk of endometrial cancer, but whether the association is independent of the number of births or other factors remains unclear. Individual-level data from 4 cohort and 13 case-control studies in the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 8,671 cases of endometrial cancer and 16,562 controls were included in the analysis. After adjustment for known risk factors, endometrial cancer risk declined with increasing age at last birth (Ptrend < 0.0001). The pooled odds ratio per 5-year increase in age at last birth was 0.87 (95% confidence interval: 0.85, 0.90). Women who last gave birth at 40 years of age or older had a 44% decreased risk compared with women who had their last birth under the age of 25 years (95% confidence interval: 47, 66). The protective association was similar across the different age-at-diagnosis groups and for the 2 major tumor histologic subtypes (type I and type II). No effect modification was observed by body mass index, parity, or exogenous hormone use. In this large pooled analysis, late age at last birth was independently associated with a reduced risk of endometrial cancer, and the reduced risk persisted for many years. PMID:22831825

Biobanking human endometrial tissue and blood specimens: standard operating procedure and importance to reproductive biology research and diagnostic development.

PubMed

Sheldon, Elizabeth; Vo, Kim Chi; McIntire, Ramsey A; Aghajanova, Lusine; Zelenko, Zara; Irwin, Juan C; Giudice, Linda C

2011-05-01

To develop a standard operating procedure (SOP) for collection, transport, storage of human endometrial tissue and blood samples, subject and specimen annotation, and establishing sample priorities. The SOP synthesizes sound scientific procedures, the literature on ischemia research, sample collection and gene expression profiling, good laboratory practices, and the authors' experience of workflow and sample quality. The National Institutes of Health, University of California, San Francisco, Human Endometrial Tissue and DNA Bank. Women undergoing endometrial biopsy or hysterectomy for nonmalignant indications. Collecting, processing, storing, distributing endometrial tissue and blood samples under approved institutional review board protocols and written informed consent from participating subjects. Standard operating procedure. The SOP addresses rigorous and consistent subject annotation, specimen processing and characterization, strict regulatory compliance, and a reference for researchers to track collection and storage times that may influence their research. The comprehensive and systematic approach to the procurement of human blood and endometrial tissue in this SOP ensures the high quality, reliability, and scientific usefulness of biospecimens made available to investigators by the National Institutes of Health, University of California, San Francisco, Human Endometrial Tissue and DNA Bank. The detail and perspective in this SOP also provides a blueprint for implementation of similar collection programs at other institutions. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Soy food and isoflavone intake and endometrial cancer risk: the Japan Public Health Center-based prospective study.

PubMed

Budhathoki, S; Iwasaki, M; Sawada, N; Yamaji, T; Shimazu, T; Sasazuki, S; Inoue, M; Tsugane, S

2015-02-01

Compared with western populations, the consumption of soy foods among Japanese is very high and the incidence of endometrial cancer very low. We evaluated the association of soy food and isoflavone intake with endometrial cancer risk in Japanese women. Prospective cohort study. Ten public health centre areas in Japan. Forty nine thousand one hundred and twenty-one women of age 45-74 years who responded to a 5-year follow-up survey questionnaire. Intakes of soy foods as well as other covariates were assessed in 1995-1998 by a self-administered food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Incidence of endometrial cancer. During an average of 12.1 years of follow up, 112 newly diagnosed endometrial cancer cases were identified. Energy-adjusted intakes of soy food and isoflavone were not associated with the risk of endometrial cancer. The multivariate-adjusted HR per 25 g/day increase in the intake of soy food was 1.02 (95% CI 0.94-1.10), and the corresponding value for isoflavone intake per 15 mg/day was 1.01 (95% CI 0.84-1.22). In this population-based prospective cohort study of Japanese women, we observed no evidence of a protective association between soy food or isoflavone intake and endometrial cancer risk. © 2014 Royal College of Obstetricians and Gynaecologists.

The potential role of elastography in differentiating between endometrial polyps and submucosal fibroids: a preliminary study

PubMed Central

2015-01-01

Endometrial polyps and submucosal fibroids are common causes of abnormal uterine bleeding (AUB) and less commonly infertility. The prevalence of such intrauterine lesions increases with age during the reproductive years, and usually decreases after menopause. The first-line imaging examination in the diagnosis of endometrial polyps as well as submucosal fibroidsis ultrasound, but its accuracy is not obvious. Elastography is an ultrasound-based imaging modality that is used to assess the stiffness of examined tissues. Considering the fact that endometrial polyps derive from soft endometrial tissue and submucosal fibroids are made of hard muscle tissue, elastography seems a perfect tool to differentiate between such lesions. I present two groups of patients with AUB and intrauterine lesions suspected on ultrasound. In the first group of patients, elastography showed that the stiffness of the lesion was similar to the endometrium and softer than the myometrium. During hysteroscopies endometrial polyps were removed. In the second group of patients, elastography showed that the stiffness of the lesion was similar to the myometrium and harder than the endometrium. During hysteroscopies submucosal fibroids were removed. In both groups, the diagnosis was confirmed by the pathological examination in all cases. It was demonstrated that with the use of elastography it is possible to assess the stiffness of intrauterine lesions, which may be useful in differentiating between endometrial polyps and submucosal fibroids. PMID:26327901

The potential role of elastography in differentiating between endometrial polyps and submucosal fibroids: a preliminary study.

PubMed

Woźniak, Sławomir

2015-06-01

Endometrial polyps and submucosal fibroids are common causes of abnormal uterine bleeding (AUB) and less commonly infertility. The prevalence of such intrauterine lesions increases with age during the reproductive years, and usually decreases after menopause. The first-line imaging examination in the diagnosis of endometrial polyps as well as submucosal fibroidsis ultrasound, but its accuracy is not obvious. Elastography is an ultrasound-based imaging modality that is used to assess the stiffness of examined tissues. Considering the fact that endometrial polyps derive from soft endometrial tissue and submucosal fibroids are made of hard muscle tissue, elastography seems a perfect tool to differentiate between such lesions. I present two groups of patients with AUB and intrauterine lesions suspected on ultrasound. In the first group of patients, elastography showed that the stiffness of the lesion was similar to the endometrium and softer than the myometrium. During hysteroscopies endometrial polyps were removed. In the second group of patients, elastography showed that the stiffness of the lesion was similar to the myometrium and harder than the endometrium. During hysteroscopies submucosal fibroids were removed. In both groups, the diagnosis was confirmed by the pathological examination in all cases. It was demonstrated that with the use of elastography it is possible to assess the stiffness of intrauterine lesions, which may be useful in differentiating between endometrial polyps and submucosal fibroids.

MicroRNA-93 Promotes Epithelial–Mesenchymal Transition of Endometrial Carcinoma Cells

PubMed Central

Sun, Kai-Xuan; Xiu, Yin-Ling; Liu, Bo-Liang; Feng, Miao-Xiao; Sang, Xiu-Bo; Zhao, Yang

2016-01-01

MicroRNA-93, derived from a paralog (miR-106b-25) of the miR-17-92 cluster, is involved in the tumorigenesis and progression of many cancers such as breast, colorectal, hepatocellular, lung, ovarian, and pancreatic cancer. However, the role of miR-93 in endometrial carcinoma and the potential molecular mechanisms involved remain unknown. Our results showed that miR-93 was overexpressed in endometrial carcinoma tissues than normal endometrial tissues. The endometrial carcinoma cell lines HEC-1B and Ishikawa were transfected with miR-93-5P, after which cell migration and invasion ability and the expression of relevant molecules were detected. MiR-93 overexpression promoted cell migration and invasion, and downregulated E-cadherin expression while increasing N-cadherin expression. Dual-luciferase reporter assay showed that miR-93 may directly bind to the 3′ untranslated region of forkhead box A1 (FOXA1); furthermore, miR-93 overexpression downregulated FOXA1 expression while miR-93 inhibitor transfection upregulated FOXA1 expression at both mRNA and protein level. In addition, transfection with the most effective FOXA1 small interfering RNA promoted both endometrial cancer cell migration and invasion, and downregulated E-cadherin expression while upregulating N-cadherin expression. Therefore, we suggest that miR-93 may promote the process of epithelial–mesenchymal transition in endometrial carcinoma cells by targeting FOXA1. PMID:27829043

Soya food intake and risk of endometrial cancer among Chinese women in Shanghai: population based case-control study

PubMed Central

Xu, Wang Hong; Zheng, Wei; Xiang, Yong Bing; Ruan, Zhi Xian; Cheng, Jia Rong; Dai, Qi; Gao, Yu Tang; Shu, Xiao Ou

2004-01-01

Objective To evaluate the association of intake of soya food, a rich source of phytoestrogens, with the risk of endometrial cancer. Design Population based case-control study, with detailed information on usual soya food intake over the past five years collected by face to face interview using a food frequency questionnaire. Setting Urban Shanghai, China. Participants 832 incident cases of endometrial cancer in women aged of 30 to 69 years diagnosed during 1997-2001 and identified from the Shanghai Cancer Registry; 846 control women frequency matched to cases on age and randomly selected from the Shanghai Residential Registry. Main outcome measures Odds ratios for risk of endometrial cancer in women with different intakes of soya foods. Results Regular consumption of soya foods, measured as amount of either soya protein or soya isoflavones, was inversely associated with the risk of endometrial cancer. Compared with women with the lowest quarter of intake, the adjusted odds ratio of endometrial cancer was reduced from 0.93 to 0.85 and 0.67 with increasing quarter of soya protein intake (P for trend 0.01). A similar inverse association was observed for soya isoflavones and soya fibre intake. The inverse association seemed to be more pronounced among women with high body mass index and waist:hip ratio. Conclusion Regular intake of soya foods is associated with a reduced risk of endometrial cancer. PMID:15136343

Novel Roles for Hypoxia and Prostaglandin E2 in the Regulation of IL-8 During Endometrial Repair

PubMed Central

Maybin, Jacqueline A.; Hirani, Nikhil; Jabbour, Henry N.; Critchley, Hilary O.D.

2011-01-01

The endometrium has a remarkable capacity for efficient repair; however, factors involved remain undefined. Premenstrual progesterone withdrawal leads to increased prostaglandin (PG) production and local hypoxia. Here we determined human endometrial expression of interleukin-8 (IL-8) and the roles of PGE2 and hypoxia in its regulation. Endometrial biopsy specimens (n = 51) were collected. Endometrial cells and explants were exposed to 100 nmol/L of PGE2 or 0.5% O2. The endometrial IL-8 concentration peaked during menstruation (P < 0.001) and had a significant proangiogenic effect. IL-8 was increased by PGE2 and hypoxia in secretory but not proliferative explants, which suggests that exposure to progesterone is essential. In vitro progesterone withdrawal induced significant IL-8 up-regulation in proliferative explants primed with progestins, but only in the presence of hypoxia. Epithelial cells treated simultaneously with PGE2 and hypoxia demonstrated synergistic increases in IL-8. Inhibition of HIF-1 by short hairpin RNA abolished hypoxic IL-8 induction, and inhibition of NF-κB by an adenoviral dominant negative inhibitor decreased PGE2-induced IL-8 expression (P > 0.05). Increased menstrual IL-8 is consistent with a role in repair. Progesterone withdrawal, hypoxia, and PGE2 regulate endometrial IL-8 by acting via HIF-1 and NF-κB. Hence, progesterone withdrawal may activate two distinct pathways to initiate endometrial repair. PMID:21356375

Resveratrol inhibits development of experimental endometriosis in vivo and reduces endometrial stromal cell invasiveness in vitro.

PubMed

Bruner-Tran, Kaylon L; Osteen, Kevin G; Taylor, Hugh S; Sokalska, Anna; Haines, Kaitlin; Duleba, Antoni J

2011-01-01

Endometriosis is a common gynecologic disorder characterized by ectopic attachment and growth of endometrial tissues. Resveratrol is a natural polyphenol with antiproliferative and anti-inflammatory properties. Our objective was to study the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro. Human endometrial tissues were obtained from healthy donors. Endometriosis was established in oophorectomized nude mice by intraperitoneal injection of endometrial tissues. Mice were treated with 17β-estradiol (8 mg, silastic capsule implants) alone (n = 16) or with resveratrol (6 mg/mouse; n = 20) for 10-12 and 18-20 days beginning 1 day after tissue injection. Mice were killed and endometrial implants were evaluated. A Matrigel invasion assay was used to examine the effects of resveratrol on HES cells. We assessed number and size of endometriotic implants in vivo and Matrigel invasion in vitro. Resveratrol decreased the number of endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10-30 μM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis.

Intracrine Androgens Enhance Decidualization and Modulate Expression of Human Endometrial Receptivity Genes

PubMed Central

Gibson, Douglas A.; Simitsidellis, Ioannis; Cousins, Fiona L.; Critchley, Hilary O. D.; Saunders, Philippa T. K.

2016-01-01

The endometrium is a complex, steroid-dependent tissue that undergoes dynamic cyclical remodelling. Transformation of stromal fibroblasts (ESC) into specialised secretory cells (decidualization) is fundamental to the establishment of a receptive endometrial microenvironment which can support and maintain pregnancy. Androgen receptors (AR) are present in ESC; in other tissues local metabolism of ovarian and adrenal-derived androgens regulate AR-dependent gene expression. We hypothesised that altered expression/activity of androgen biosynthetic enzymes would regulate tissue availability of bioactive androgens and the process of decidualization. Primary human ESC were treated in vitro for 1–8 days with progesterone and cAMP (decidualized) in the presence or absence of the AR antagonist flutamide. Time and treatment-dependent changes in genes essential for a) intra-tissue biosynthesis of androgens (5α-reductase/SRD5A1, aldo-keto reductase family 1 member C3/AKR1C3), b) establishment of endometrial decidualization (IGFBP1, prolactin) and c) endometrial receptivity (SPP1, MAOA, EDNRB) were measured. Decidualization of ESC resulted in significant time-dependent changes in expression of AKR1C3 and SRD5A1 and secretion of T/DHT. Addition of flutamide significantly reduced secretion of IGFBP1 and prolactin and altered the expression of endometrial receptivity markers. Intracrine biosynthesis of endometrial androgens during decidualization may play a key role in endometrial receptivity and offer a novel target for fertility treatment. PMID:26817618

Intracrine Androgens Enhance Decidualization and Modulate Expression of Human Endometrial Receptivity Genes.

PubMed

Gibson, Douglas A; Simitsidellis, Ioannis; Cousins, Fiona L; Critchley, Hilary O D; Saunders, Philippa T K

2016-01-28

The endometrium is a complex, steroid-dependent tissue that undergoes dynamic cyclical remodelling. Transformation of stromal fibroblasts (ESC) into specialised secretory cells (decidualization) is fundamental to the establishment of a receptive endometrial microenvironment which can support and maintain pregnancy. Androgen receptors (AR) are present in ESC; in other tissues local metabolism of ovarian and adrenal-derived androgens regulate AR-dependent gene expression. We hypothesised that altered expression/activity of androgen biosynthetic enzymes would regulate tissue availability of bioactive androgens and the process of decidualization. Primary human ESC were treated in vitro for 1-8 days with progesterone and cAMP (decidualized) in the presence or absence of the AR antagonist flutamide. Time and treatment-dependent changes in genes essential for a) intra-tissue biosynthesis of androgens (5α-reductase/SRD5A1, aldo-keto reductase family 1 member C3/AKR1C3), b) establishment of endometrial decidualization (IGFBP1, prolactin) and c) endometrial receptivity (SPP1, MAOA, EDNRB) were measured. Decidualization of ESC resulted in significant time-dependent changes in expression of AKR1C3 and SRD5A1 and secretion of T/DHT. Addition of flutamide significantly reduced secretion of IGFBP1 and prolactin and altered the expression of endometrial receptivity markers. Intracrine biosynthesis of endometrial androgens during decidualization may play a key role in endometrial receptivity and offer a novel target for fertility treatment.

Constituents of neutrophil extracellular traps induce in vitro collagen formation in mare endometrium.

PubMed

Rebordão, Maria Rosa; Amaral, Ana; Lukasik, Karolina; Szóstek-Mioduchowska, Anna; Pinto-Bravo, Pedro; Galvão, António; Skarzynski, Dariusz J; Ferreira-Dias, Graça

2018-06-01

Neutrophil extracellular traps (NETs) are DNA complexes carrying nuclear and cytoplasmic proteins, such as elastase (ELA), cathepsin-G (CAT) and myeloperoxidase (MPO). Mare endometrosis is a chronic degenerative process characterized by excessive collagen in endometrium. While NETs fight bacteria that cause endometritis, they may trigger endometrial fibrogenesis. The aim was to evaluate the in vitro effect of some NETs components on mare endometrial fibrogenesis and determine its relationship with histopathology or estrous cycle. Endometrial explants were incubated with NETs components (ELA, CAT, MPO or oxytocin). Collagen type I (COL1) protein and type I and III (COL3) gene transcription were evaluated in follicular and mid-luteal phases endometria (Kenney and Doig type I/IIA and IIB/III). Increased COL1 occurred with all NETs proteins, although endometrial response to each NETs protease depended on estrous cycle and/or endometrial category. Since ELA enhanced COL1 production, NETs persistence might be linked to endometrosis. Estrous cycle influenced COL1 protein concentration and COL3 transcripts, suggesting that follicular phase may favor endometrial collagen production. However, luteal phase endometria with moderate or severe lesions may be also susceptible to fibrotic effects of NETs constituents. These data propose that NETs involvement in chronic endometritis in mares may act as putative endometrial fibrogenic mediators. Copyright © 2018 Elsevier Inc. All rights reserved.

miR-888: A Novel Cancer-Testis Antigen that Targets the Progesterone Receptor in Endometrial Cancer12

PubMed Central

Hovey, Adriann M.; Devor, Eric J.; Breheny, Patrick J.; Mott, Sarah L.; Dai, Donghai; Thiel, Kristina W.; Leslie, Kimberly K.

2015-01-01

Cancer-testis (CT) antigens are a large family of genes that are selectively expressed in human testis germ cells, overexpressed in a variety of tumors and predominantly located on the X chromosome. To date, all known CT antigens are protein-coding genes. Here, we identify miR-888 as the first miRNA with features characteristic of a CT antigen. In a panel of 21 normal human tissues, miR-888 expression was high in testes and minimal or absent in all other examined tissues. In situ hybridization localized miR-888 expression specifically to the early stages of sperm development within the testes. Using The Cancer Genome Atlas database, we discovered that miR-888 was predominately expressed in endometrial tumors, with a significant association to high-grade tumors and increased percent invasion. In a separate panel of endometrial tumor specimens, we validated overexpression of miR-888 by real-time polymerase chain reaction. In addition, miR-888 expression was highest in endometrial carcinosarcoma, a rare and aggressive type of endometrial tumor. Moreover, we identified the progesterone receptor (PR), a potent endometrial tumor suppressor, as a direct target of miR-888. These data define miR-888 as the first miRNA CT antigen and a potential mediator of an aggressive endometrial tumor phenotype through down-regulation of PR. PMID:25926074

Clinical utility of progesterone receptor modulators and their effect on the endometrium.

PubMed

Spitz, Irving M

2009-08-01

In view of the spate of recent publications related to mifepristone and some second generation progesterone receptor modulators (PRMs), this appears to be an opportune time to view the clinical status of these compounds. Randomized double-blind placebo-controlled trials have been conducted with mifepristone, CDB-4124 (Proellex), CDB-2914 (VA 2914, Ulipristal) and asoprisnil (J867). All these PRMs are effective in the treatment of uterine fibroids where they are associated with a reduction in pain, bleeding and improvement in quality of life and decrease in fibroid size. CDB-4124 is also efficacious in endometriosis. Long-term treatment with PRMs may be associated with endometrial thickening on ultrasound and there have been reports of endometrial hyperplasia. Several reassuring recent publications have done much to explain the mechanism underlying these endometrial changes. The most common histological finding is cystic glandular dilatation often associated with both admixed estrogen (mitotic) and progestin (secretory) epithelial effects. This histology has not been previously encountered in clinical practice and should not be confused with endometrial hyperplasia. The endometrial thickness is related to this cystic glandular dilatation. At this stage of development, PRMs cannot be administered for longer than 3 or 4 months. Even over this time, there is improvement of symptoms associated with fibroids and endometriosis. Clinicians and pathologists need to be aware that the endometrial thickening and histological appearance do not represent endometrial hyperplasia.

Infertility and incident endometrial cancer risk: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2)

PubMed Central

Yang, H P; Cook, L S; Weiderpass, E; Adami, H-O; Anderson, K E; Cai, H; Cerhan, J R; Clendenen, T V; Felix, A S; Friedenreich, C M; Garcia-Closas, M; Goodman, M T; Liang, X; Lissowska, J; Lu, L; Magliocco, A M; McCann, S E; Moysich, K B; Olson, S H; Petruzella, S; Pike, M C; Polidoro, S; Ricceri, F; Risch, H A; Sacerdote, C; Setiawan, V W; Shu, X O; Spurdle, A B; Trabert, B; Webb, P M; Wentzensen, N; Xiang, Y-B; Xu, Y; Yu, H; Zeleniuch-Jacquotte, A; Brinton, L A

2015-01-01

Background: Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes. Methods: We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59–1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13–1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer. Conclusions: Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters. PMID:25688738

Carboplatin and Paclitaxel With or Without Cisplatin and Radiation Therapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IVA Endometrial Cancer

ClinicalTrials.gov

2018-01-09

Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Stage IA Uterine Corpus Cancer; Stage IB Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Uterine Corpus Cancer; Stage IVA Uterine Corpus Cancer

Virtual Reality Hysteroscopy

PubMed

Levy

1996-08-01

New interactive computer technologies are having a significant influence on medical education, training, and practice. The newest innovation in computer technology, virtual reality, allows an individual to be immersed in a dynamic computer-generated, three-dimensional environment and can provide realistic simulations of surgical procedures. A new virtual reality hysteroscope passes through a sensing device that synchronizes movements with a three-dimensional model of a uterus. Force feedback is incorporated into this model, so the user actually experiences the collision of an instrument against the uterine wall or the sensation of the resistance or drag of a resectoscope as it cuts through a myoma in a virtual environment. A variety of intrauterine pathologies and procedures are simulated, including hyperplasia, cancer, resection of a uterine septum, polyp, or myoma, and endometrial ablation. This technology will be incorporated into comprehensive training programs that will objectively assess hand-eye coordination and procedural skills. It is possible that by incorporating virtual reality into hysteroscopic training programs, a decrease in the learning curve and the number of complications presently associated with the procedures may be realized. Prospective studies are required to assess these potential benefits.

Prognosis of women with stage I endometrioid endometrial cancer and synchronous stage I endometrioid ovarian cancer.

PubMed

Matsuo, Koji; Machida, Hiroko; Frimer, Marina; Marcus, Jenna Z; Pejovic, Tanja; Roman, Lynda D; Wright, Jason D

2017-12-01

Synchronous endometrial and ovarian cancer with endometrioid histology at two cancer sites typically presents with early-stage disease and is thought to have a good prognosis. We examined the survival of women with early-stage endometrioid endometrial cancer who had synchronous early-stage endometrioid ovarian cancer. This is a retrospective case-control study examining the Surveillance, Epidemiology, and End Result Program between 1973 and 2013. Survival of women with stage I endometrioid endometrial cancer with stage I endometrioid ovarian cancer (n=839) were compared to women with stage I endometrioid endometrial cancer without synchronous ovarian cancer (n=123,692) after propensity score matching. Women with synchronous stage I endometrioid ovarian cancer were more likely to be diagnosed recently, be younger, have stage IA disease, grade 1 tumors, to have undergone lymphadenectomy, and were less likely to receive radiotherapy compared to those without synchronous ovarian cancer (all, P<0.001). In a propensity score matched model, the presence of synchronous ovarian cancer was not associated with endometrial cancer-specific survival (10-year rates 96.0% versus 95.3%, P=0.97) or overall survival (85.6% versus 87.2%, P=0.10). Among tumors with concordant grades at the two cancer sites, survival was similar regardless of presence of synchronous ovarian tumors (grade 1 tumors, 10-year rate for overall survival, 88.2% versus 89.1%, P=0.40; and grade 2 tumors, 84.0% versus 85.8%, P=0.78). Women with stage I endometrioid endometrial cancer with synchronous stage I endometrioid ovarian cancer have a survival outcome similar to those with stage I endometrioid endometrial cancer without synchronous ovarian cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Utility of MLH1 Methylation Analysis in the Clinical Evaluation of Lynch Syndrome in Women with Endometrial Cancer

PubMed Central

Bruegl, Amanda S.; Djordjevic, Bojana; Urbauer, Diana L.; Westin, Shannon N.; Soliman, Pamela T.; Lu, Karen H.; Luthra, Rajyalakshmi; Broaddus, Russell R.

2013-01-01

Clinical screening criteria, such as young age of endometrial cancer diagnosis and family history of signature cancers, have traditionally been used to identify women with Lynch Syndrome, which is caused by mutation of a DNA mismatch repair gene. Immunohistochemistry and microsatellite instability analysis have evolved as important screening tools to evaluate endometrial cancer patients for Lynch Syndrome. A complicating factor is that 15-20% of sporadic endometrial cancers have immunohistochemical loss of the DNA mismatch repair protein MLH1 and high levels of microsatellite instability due to methylation of MLH1. The PCR-based MLH1 methylation assay potentially resolves this issue, yet many clinical laboratories do not perform this assay. The objective of this study was to determine if clinical and pathologic features help to distinguish sporadic endometrial carcinomas with MLH1 loss secondary to MLH1 methylation from Lynch Syndrome-associated endometrial carcinomas with MLH1 loss and absence of MLH1 methylation. Of 337 endometrial carcinomas examined, 54 had immunohistochemical loss of MLH1. 40/54 had MLH1 methylation and were designated as sporadic, while 14/54 lacked MLH1 methylation and were designated as Lynch Syndrome. Diabetes and deep myometrial invasion were associated with Lynch Syndrome; no other clinical or pathological variable distinguished the 2 groups. Combining Society of Gynecologic Oncology screening criteria with these 2 features accurately captured all Lynch Syndrome cases, but with low specificity. In summary, no single clinical/pathologic feature or screening criteria tool accurately identified all Lynch Syndrome-associated endometrial carcinomas, highlighting the importance of the MLH1 methylation assay in the clinical evaluation of these patients. PMID:23888949

Utility of MLH1 methylation analysis in the clinical evaluation of Lynch Syndrome in women with endometrial cancer.

PubMed

Bruegl, Amanda S; Djordjevic, Bojana; Urbauer, Diana L; Westin, Shannon N; Soliman, Pamela T; Lu, Karen H; Luthra, Rajyalakshmi; Broaddus, Russell R

2014-01-01

Clinical screening criteria, such as young age of endometrial cancer diagnosis and family history of signature cancers, have traditionally been used to identify women with Lynch Syndrome, which is caused by mutation of a DNA mismatch repair gene. Immunohistochemistry and microsatellite instability analysis have evolved as important screening tools to evaluate endometrial cancer patients for Lynch Syndrome. A complicating factor is that 15-20% of sporadic endometrial cancers have immunohistochemical loss of the DNA mismatch repair protein MLH1 and high levels of microsatellite instability due to methylation of MLH1. The PCR-based MLH1 methylation assay potentially resolves this issue, yet many clinical laboratories do not perform this assay. The objective of this study was to determine if clinical and pathologic features help to distinguish sporadic endometrial carcinomas with MLH1 loss secondary to MLH1 methylation from Lynch Syndrome-associated endometrial carcinomas with MLH1 loss and absence of MLH1 methylation. Of 337 endometrial carcinomas examined, 54 had immunohistochemical loss of MLH1. 40/54 had MLH1 methylation and were designated as sporadic, while 14/54 lacked MLH1 methylation and were designated as Lynch Syndrome. Diabetes and deep myometrial invasion were associated with Lynch Syndrome; no other clinical or pathological variable distinguished the 2 groups. Combining Society of Gynecologic Oncology screening criteria with these 2 features accurately captured all Lynch Syndrome cases, but with low specificity. In summary, no single clinical/pathologic feature or screening criteria tool accurately identified all Lynch Syndrome-associated endometrial carcinomas, highlighting the importance of the MLH1 methylation assay in the clinical evaluation of these patients.

Endometrial stem cells repair injured endometrium and induce angiogenesis via AKT and ERK pathways.

PubMed

Zhang, Yanling; Lin, Xiaona; Dai, Yongdong; Hu, Xiaoxiao; Zhu, Haiyan; Jiang, Yinshen; Zhang, Songying

2016-11-01

Intrauterine adhesions are common acquired endometrial syndromes secondary to endometrial injury, with limited effective therapies. Recently, several studies have reported that bone marrow stem cells (BMSCs) could repair injured endometrium in animal experiments. However, the role of stem cells in endometrial injury repair and its therapeutic mechanisms remain unclear. Here, we established mouse endometrial injury model and examined the benefit of human endometrial mesenchymal stem cells derived from menstrual blood (MenSCs) in restoration of injured endometrium. Injured endometrium exhibited significantly accelerated restoration at Day 7 after MenSCs transplantation, with increased endometrial thickness and microvessel density. Moreover, the fertility of mice with injured endometrium was improved, with higher conception rate (53.57% vs 14.29%, P = 0.014) and larger embryo number (3.1 ± 0.6 vs 0.9 ± 0.7, P = 0.030) in MenSCs group than control group, while no difference was found in undamaged horns between two groups. Conditioned medium from MenSCs (MenSCs-CM) could decrease H2O2-induced apoptosis of human umbilical vein endothelial cells (HUVECs) and promote proliferation, migration and angiogenesis. Angiogenesis effect of MenSCs-CM was also confirmed in Matrigel plug assay in mice. Furthermore, we discovered that MenSCs-CM could activate AKT and ERK pathways and induce the overexpression of eNOS, VEGFA, VEGFR1, VEGFR2 and TIE2 in HUVECs, which are critical in MenSCs-CM-induced angiogenesis. Angiogenesis induced by MenSCs-CM could be reversed by inhibitors of AKT and/or ERK. Taken together, we concluded that MenSCs could restore injured endometrium and improve the fertility of the endometrial injury mice, which was partially attributed to angiogenesis induced by MenSCs. © 2016 Society for Reproduction and Fertility.

Steroids Regulate CXCL4 in the Human Endometrium During Menstruation to Enable Efficient Endometrial Repair

PubMed Central

Maybin, Jacqueline A.; Thiruchelvam, Uma; Madhra, Mayank; Saunders, Philippa T.K.

2017-01-01

Context: Repair of the endometrial surface at menstruation must be efficient to minimize blood loss and optimize reproductive function. The mechanism and regulation of endometrial repair remain undefined. Objective: To determine the presence/regulation of CXCL4 in the human endometrium as a putative repair factor at menses. Patients/Setting: Endometrial tissue was collected throughout the menstrual cycle from healthy women attending the gynecology department. Menstrual blood loss was objectively measured in a subset, and heavy menstrual bleeding (HMB) was defined as >80 mL per cycle. Monocytes were isolated from peripheral blood. Design: CXCL4 messenger RNA (mRNA) and protein were identified by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The function/regulation of endometrial CXCL4 was explored by in vitro cell culture. Results: CXCL4 mRNA concentrations were significantly increased during menstruation. Intense staining for CXCL4 was detected in late secretory and menstrual tissue, localized to stromal, epithelial and endothelial cells. Colocalization identified positive staining in CD68+ macrophages. Treatment of human endometrial stromal and endothelial cells (hESCs and HEECs, respectively) with steroids revealed differential regulation of CXCL4. Progesterone withdrawal resulted in significant increases in CXCL4 mRNA and protein in hESCs, whereas cortisol significantly increased CXCL4 in HEECs. In women with HMB, CXCL4 was reduced in endothelial cells during the menstrual phase compared with women with normal menstrual bleeding. Cortisol-exposed macrophages displayed increased chemotaxis toward CXCL4 compared with macrophages incubated with estrogen or progesterone. Conclusions: These data implicate CXCL4 in endometrial repair after menses. Reduced cortisol at the time of menses may contribute to delayed endometrial repair and HMB, in part by mechanisms involving aberrant expression of CXCL4. PMID:28323919

Canadian Consensus-based and Evidence-based Guidelines for Benign Endometrial Pathology Reporting in Biopsy Material.

PubMed

Parra-Herran, Carlos; Cesari, Matthew; Djordjevic, Bojana; Grondin, Katherine; Kinloch, Mary; Köbel, Martin; Pirzada, Amrah; Plotkin, Anna; Gilks, C Blake

2018-04-19

Standardized terminology has proven benefits in cancer reporting; in contrast, reporting of benign diagnoses in endometrial biopsy currently lacks such standardization. Unification and update on the lexicon can provide the structure and consistency needed for optimal patient care and quality assurance purposes. The Special Interest Group in Gynecologic Pathology of the Canadian Association of Pathologists-Association Canadienne des Pathologistes (CAP-ACP) embarked in an initiative to address the current need for consensus terminology in benign endometrial biopsy pathology reporting. Nine members of the Special Interest Group developed a guideline for structured diagnosis of benign endometrial pathology through critical appraisal of the available peer-reviewed literature and joint discussions. The first version of the document was circulated for feedback to a group of professionals in akin fields, the CAP-ACP Executive Committee and the CAP-ACP general membership. The final 1-page document included 17 diagnostic terms comprising the most common benign endometrial entities, as well as explanatory notes for pathologists. The proposed terminology was implemented in the practice of 5 pathologists from the group, who applied the guideline to all benign endometrial biopsies over a 2-wk period. A total of 212 benign endometrial biopsies were evaluated in this implementation step; the recommended terminology adequately covered the diagnosis in 203 cases (95.8%). A list of terminology for benign endometrial biopsy reporting, based on expert consensus and critical appraisal of the available literature, is presented. On the basis of our results of implementation at multiple centers, the proposed guideline can successfully cover the large majority of diagnostic scenarios. The document has the potential to positively impact patient care, promote quality assurance, and facilitate research initiatives aimed at improving histopathologic assessment of benign endometrium.

G protein-coupled estrogen receptor (GPER) expression in endometrial adenocarcinoma and effect of agonist G-1 on growth of endometrial adenocarcinoma cell lines.

PubMed

Skrzypczak, Maciej; Schüler, Susanne; Lattrich, Claus; Ignatov, Atanas; Ortmann, Olaf; Treeck, Oliver

2013-11-01

The G protein-coupled estrogen receptor (GPER, GPR30) is suggested to be involved in non-nuclear estrogen signaling and is expressed in a variety of hormone dependent cancer entities. This study was performed to further elucidate the role of this receptor in endometrial adenocarcinoma. We first analyzed GPER expression at the mRNA level in 88 endometrial cancer or normal endometrial tissue samples and compared it to those of nuclear steroid hormone receptors. GPER transcript levels were found to be about 6-fold reduced, but still present in endometrial cancer. Expression of this receptor was decreased in all grading subgroups when compared to pre- or postmenopausal endometrium. GPER mRNA expression was associated with PR mRNA levels (Spearman's rho 0.4610, p<0.001). We then tested the effect of the GPER ligand G-1 on growth of three endometrial cancer cell lines with different GPER expression. GPER protein levels were highest in RL95-2 cells, moderate in HEC-1A cells and not detectable in HEC-1B cells. The moderate expression level in HEC-1A cells was similar to average tumor tissue expression. Treatment with G-1 significantly inhibited growth of the GPER-positive cell lines RL95-2 and HEC-1A in a dose-dependent manner, whereas the GPER-negative line HEC-1B was not affected. Though GPER transcript levels were found to be reduced in endometrial cancer, our in vitro data suggest that moderate GPER expression might be sufficient to mediate growth-inhibitory effects triggered by its agonist G-1. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of the percentage of body fat on surgical, clinical and pathological outcomes in women with endometrial cancer.

PubMed

Kerimoglu, Ozlem Secilmis; Pekin, Aybike; Yilmaz, Setenay Arzu; Yavas, Guler; Beyhekim, Fatma; Demirtaş, Ayşe Ayda; Dogan, Nasuh Utku; İlhan, Tolgay Tuyan; Celik, Cetin

2015-03-01

This study used the measure of percentage of body fat (%BF) to define obesity and evaluated the effect of percentage of %BF on clinical, surgical and pathological features in women with endometrial cancer. Between 2011 and 2013, bioelectrical impedance analysis and body size measurements of 94 patients whose endometrial biopsy revealed endometrial cancer were obtained. Patients were divided into two groups according to body mass index (BMI) (normal, < 30 kg/m(2); elevated, ≥ 30 kg/m(2)), and also classified by %BF (normal, < 32%; elevated, ≥ 32%). The patients' mean age was 55.0 ± 10.9 years. Mean %BF and BMI were 40.8% ± 9.8% and 32.9 ± 7.5, respectively. Eighty-three (88%) patients were obese according to %BF; 54 (57%) were obese according to BMI. Patients with elevated %BF were more likely to have less than 50% myometrial invasion (P = 0.004). Significantly more para-aortic lymph nodes were retrieved in patients with normal %BF or BMI (P < 0.001, P < 0.001). Patients with elevated %BF had longer operating times (P = 0.043) and were more likely to have stage I disease than patients with normal %BF (P < 0.001). Endometrial cancer patients with an elevated %BF are more likely to have stage I disease and less than 50% myometrial invasion than patients with normal %BF. Defining obesity by BF may provide better estimation of obesity prevalence in patients with endometrial cancer and further understanding the relationship between BF with endometrial cancer may give more information about the effects of obesity on endometrial cancer. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Endometrial nitric oxide synthase activity in mares susceptible or resistant to persistent breeding-induced endometritis and the effect of a specific iNOS inhibitor in vitro.

PubMed

Khan, F A; Chenier, T S; Foster, R A; Hewson, J; Scholtz, E L

2018-06-01

Emerging research suggests that the nitric oxide system may play a role in persistent breeding-induced endometritis (PBIE) in the mare. Differences in uterine nitric oxide (NO) levels between mares susceptible or resistant to PBIE and a dose-dependent inhibitory effect of NO on uterine contractility have been demonstrated. The objectives of this study were to investigate the difference in total nitric oxide synthase (NOS) activity of the endometrium between susceptible and resistant mares and the effect of a specific inducible nitric oxide synthase (iNOS) inhibitor on the endometrial NOS activity in vitro. Six susceptible and six resistant mares were selected based on preset criteria and the results of an intrauterine challenge with killed spermatozoa during oestrus. Endometrial biopsy samples were collected 24 hr post-challenge and cultured at 37°C for 24 hr in L-arginine supplemented minimum essential medium with or without a specific iNOS inhibitor (1,400 W dihydrochloride, 1 mM). The medium and the cultured endometrial tissue were collected after 24 hr of culture and assayed for NO and total protein, respectively. Total NO content of the medium, normalized to endometrial tissue wet weight or total protein, was used as a measure of endometrial NOS activity. Non-parametric tests were applied for statistical analysis. Susceptible mares had significantly greater endometrial NOS activity than resistant mares. The iNOS inhibitor treatment significantly reduced NOS activity in endometrial samples derived from susceptible and resistant mares. These findings provide a basis for in vivo testing of specific iNOS inhibitors as preventative or therapeutic options for PBIE in mares. © 2018 Blackwell Verlag GmbH.

Cryopreservation and Recovery of Human Endometrial Epithelial Cells with High Viability, Purity, and Functional Fidelity

PubMed Central

Chen, Joseph C.; Hoffman, Jacquelyn R.; Arora, Ripla; Perrone, Lila A.; Gonzalez-Gomez, Christian J; Vo, Kim Chi; Laird, Diana J.; Irwin, Juan C.; Giudice, Linda C.

2015-01-01

Objective To develop a protocol for cryopreservation and recovery of human endometrial epithelial cells (eEC) retaining molecular and functional characteristics of endometrial epithelium in vivo. Design This is an in vitro study using human endometrial cells. Setting University research laboratory. Patients Endometrial biopsies were obtained from premenopausal women undergoing benign gynecological procedures. Interventions Primary eEC were cryopreserved in 1% fetal bovine serum (FBS)/10% dimethyl sulfoxide (DMSO) in Defined Keratinocyte Serum Free Medium (KSFM). Recovered cells were observed for endometrial stromal fibroblast (eSF) contamination and subsequently evaluated for morphology, gene expression, and functional characteristics of freshly cultured eECs and in vivo endometrial epithelium. Main Outcome Measures Analysis of eEC morphology and the absence of eSF contamination; evaluation of epithelial-specific gene and protein expression; assessment of epithelial polarity. Results eEC recovered after cryopreservation (n=5) displayed epithelial morphology and expressed E-cadherin (CDH1), occludin (OCLN), claudin1 (CLDN1), and keratin18 (KRT18). Compared to eSF, recovered eEC displayed increased (P<0.05) expression of epithelial-specific genes AREG, CDH1, DEFB4A, MMP7, and WNT7A, while exhibiting low-to-undetectable (P<0.05) stromal-specific genes COL6A3, HOXA11, MMP2, PDGFRB, and WNT5A. Recovered eEC secrete levels of cytokines and growth factors comparable to freshly cultured eEC. Recovered eEC can formed a polarized monolayer with high transepithelial electrical resistance (TER) and impermeability to small molecules, and expressed apical/basolateral localization of CDH1 and apical localization of OCLN. Conclusion We have developed a protocol for cryopreservation of eEC in which recovered cells after thawing demonstrate morphological, transcriptomic, and functional characteristics of human endometrial epithelium in vivo. PMID:26515378

Obesity-related hormones and endometrial cancer among postmenopausal women: a nested case–control study within the B~FIT cohort

PubMed Central

Dallal, Cher M; Brinton, Louise A; Bauer, Douglas C; Buist, Diana S M; Cauley, Jane A; Hue, Trisha F; LaCroix, Andrea; Tice, Jeffrey A; Chia, Chia; Falk, Roni; Pfeiffer, Ruth; Pollak, Michael; Veenstra, Timothy D; Xu, Xia; Lacey, James V

2014-01-01

Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case–control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n = 15 595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992–1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m2), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (ORT3 vs T1 = 2.96; 95% CI, 1.21–7.25; P trend <0.01). After further adjustment for BMI, the estimates were attenuated and the positive trend was no longer statistically significant (ORT3 vs T1 = 2.11; 95% CI, 0.69–6.44; P trend = 0.18). No significant associations were observed with adiponectin or HMW adiponectin and endometrial cancer. Our findings with leptin suggest that the leptin–BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity–endometrial cancer associations. PMID:23222000

Obesity-related hormones and endometrial cancer among postmenopausal women: a nested case-control study within the B~FIT cohort.

PubMed

Dallal, Cher M; Brinton, Louise A; Bauer, Douglas C; Buist, Diana S M; Cauley, Jane A; Hue, Trisha F; Lacroix, Andrea; Tice, Jeffrey A; Chia, Victoria M; Falk, Roni; Pfeiffer, Ruth; Pollak, Michael; Veenstra, Timothy D; Xu, Xia; Lacey, James V

2013-02-01

Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case-control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n=15,595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992-1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m(2)), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (OR(T3 vs T1)=2.96; 95% CI, 1.21-7.25; P trend <0.01). After further adjustment for BMI, the estimates were attenuated and the positive trend was no longer statistically significant (OR(T3 vs T1)=2.11; 95% CI, 0.69-6.44; P trend=0.18). No significant associations were observed with adiponectin or HMW adiponectin and endometrial cancer. Our findings with leptin suggest that the leptin-BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity-endometrial cancer associations.

Inhibition of osteopontin suppresses in vitro and in vivo angiogenesis in endometrial cancer.

PubMed

Du, Xue-lian; Jiang, Tao; Sheng, Xiu-gui; Gao, Rong; Li, Qing-shui

2009-12-01

Osteopontin (OPN) has been found to play an important role in tumor angiogenesis in recent years. Our previous studies have shown that OPN is overexpressed in tumor-associated human endometrial endothelial cells (HEECs) isolated from tissue samples of patients with endometrial cancer. In the present study, we aimed to further determine the role of OPN in endometrial cancer-associated angiogenesis. We knock down OPN expression in HEECs and human endometrial cancer Ishikawa (ISK) cells using the small interference RNA method, and then evaluate the effects of OPN on endometrial cancer-associated angiogenesis by in vivo mouse studies and in vitro assays. Our results revealed that proliferative activity of HEECs and ISK cells in vitro was not affected by transfection with the siOPN-RNA (P>0.05). Inhibition of OPN expression in HEECs reduced the cell migration, with the percentage of repaired area of 36.32+/-2.88 vs. 8.54+/-1.13 (P=0.007). HEEC/siOPN and ISK/siOPN demonstrated 67.4% and 51.2% decreased invasiveness compared with controls, respectively (P<0.05). The number of branched points per well was obviously lower in HEEC/siOPN than that in HEEC/Control (32.46+/-17.10 vs. 53.15+/-15.44, P=0.021). Furthermore, ISK cells transfected with OPN siRNA formed smaller tumor in mice and led to a lower microvessel density, i.e., angiogenesis, in transplanted tumors of mice than scrambled siRNA controls (12.88+/-7.14 vs. 28.42+/-9.69 vessels per HPF, P=0.019). These data confirm the positive role of OPN in endometrial cancer-associated angiogenesis and might be of great benefit for finding rational approach in endometrial cancer therapy.

Steroids Regulate CXCL4 in the Human Endometrium During Menstruation to Enable Efficient Endometrial Repair.

PubMed

Maybin, Jacqueline A; Thiruchelvam, Uma; Madhra, Mayank; Saunders, Philippa T K; Critchley, Hilary O D

2017-06-01

Repair of the endometrial surface at menstruation must be efficient to minimize blood loss and optimize reproductive function. The mechanism and regulation of endometrial repair remain undefined. To determine the presence/regulation of CXCL4 in the human endometrium as a putative repair factor at menses. Endometrial tissue was collected throughout the menstrual cycle from healthy women attending the gynecology department. Menstrual blood loss was objectively measured in a subset, and heavy menstrual bleeding (HMB) was defined as >80 mL per cycle. Monocytes were isolated from peripheral blood. CXCL4 messenger RNA (mRNA) and protein were identified by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The function/regulation of endometrial CXCL4 was explored by in vitro cell culture. CXCL4 mRNA concentrations were significantly increased during menstruation. Intense staining for CXCL4 was detected in late secretory and menstrual tissue, localized to stromal, epithelial and endothelial cells. Colocalization identified positive staining in CD68+ macrophages. Treatment of human endometrial stromal and endothelial cells (hESCs and HEECs, respectively) with steroids revealed differential regulation of CXCL4. Progesterone withdrawal resulted in significant increases in CXCL4 mRNA and protein in hESCs, whereas cortisol significantly increased CXCL4 in HEECs. In women with HMB, CXCL4 was reduced in endothelial cells during the menstrual phase compared with women with normal menstrual bleeding. Cortisol-exposed macrophages displayed increased chemotaxis toward CXCL4 compared with macrophages incubated with estrogen or progesterone. These data implicate CXCL4 in endometrial repair after menses. Reduced cortisol at the time of menses may contribute to delayed endometrial repair and HMB, in part by mechanisms involving aberrant expression of CXCL4. Copyright © 2017 by the Endocrine Society

Investigation of dietary factors and endometrial cancer risk using a nutrient-wide association study approach in the EPIC and Nurses' Health Study (NHS) and NHSII.

PubMed

Merritt, Melissa A; Tzoulaki, Ioanna; Tworoger, Shelley S; De Vivo, Immaculata; Hankinson, Susan E; Fernandes, Judy; Tsilidis, Konstantinos K; Weiderpass, Elisabete; Tjønneland, Anne; Petersen, Kristina E N; Dahm, Christina C; Overvad, Kim; Dossus, Laure; Boutron-Ruault, Marie-Christine; Fagherazzi, Guy; Fortner, Renée T; Kaaks, Rudolf; Aleksandrova, Krasimira; Boeing, Heiner; Trichopoulou, Antonia; Bamia, Christina; Trichopoulos, Dimitrios; Palli, Domenico; Grioni, Sara; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Bueno-de-Mesquita, H Bas; Onland-Moret, N Charlotte; Peeters, Petra H; Gram, Inger T; Skeie, Guri; Quirós, J Ramón; Duell, Eric J; Sánchez, María-José; Salmerón, D; Barricarte, Aurelio; Chamosa, Saioa; Ericson, Ulrica; Sonestedt, Emily; Nilsson, Lena Maria; Idahl, Annika; Khaw, Kay-Tee; Wareham, Nicholas; Travis, Ruth C; Rinaldi, Sabina; Romieu, Isabelle; Patel, Chirag J; Riboli, Elio; Gunter, Marc J

2015-02-01

Data on the role of dietary factors in endometrial cancer development are limited and inconsistent. We applied a "nutrient-wide association study" approach to systematically evaluate dietary risk associations for endometrial cancer while controlling for multiple hypothesis tests using the false discovery rate (FDR) and validating the results in an independent cohort. We evaluated endometrial cancer risk associations for dietary intake of 84 foods and nutrients based on dietary questionnaires in three prospective studies, the European Prospective Investigation into Cancer and Nutrition (EPIC; N = 1,303 cases) followed by validation of nine foods/nutrients (FDR ≤ 0.10) in the Nurses' Health Studies (NHS/NHSII; N = 1,531 cases). Cox regression models were used to estimate HRs and 95% confidence intervals (CI). In multivariate adjusted comparisons of the extreme categories of intake at baseline, coffee was inversely associated with endometrial cancer risk (EPIC, median intake 750 g/day vs. 8.6; HR, 0.81; 95% CI, 0.68-0.97, Ptrend = 0.09; NHS/NHSII, median intake 1067 g/day vs. none; HR, 0.82; 95% CI, 0.70-0.96, Ptrend = 0.04). Eight other dietary factors that were associated with endometrial cancer risk in the EPIC study (total fat, monounsaturated fat, carbohydrates, phosphorus, butter, yogurt, cheese, and potatoes) were not confirmed in the NHS/NHSII. Our findings suggest that coffee intake may be inversely associated with endometrial cancer risk. Further data are needed to confirm these findings and to examine the mechanisms linking coffee intake to endometrial cancer risk to develop improved prevention strategies. ©2015 American Association for Cancer Research.

Time interval between endometrial biopsy and surgical staging for type I endometrial cancer: association between tumor characteristics and survival outcome.

PubMed

Matsuo, Koji; Opper, Neisha R; Ciccone, Marcia A; Garcia, Jocelyn; Tierney, Katherine E; Baba, Tsukasa; Muderspach, Laila I; Roman, Lynda D

2015-02-01

To examine whether wait time between endometrial biopsy and surgical staging correlates with tumor characteristics and affects survival outcomes in patients with type I endometrial cancer. A retrospective study was conducted to examine patients with grade 1 and 2 endometrioid adenocarcinoma diagnosed by preoperative endometrial biopsy who subsequently underwent hysterectomy-based surgical staging between 2000 and 2013. Patients who received neoadjuvant chemotherapy or hormonal treatment were excluded. Time interval and grade change between endometrial biopsy and hysterectomy were correlated to demographics and survival outcomes. Median wait time was 57 days (range 1-177 days) among 435 patients. Upgrading of the tumor to grade 3 in the hysterectomy specimen was seen in 4.7% of 321 tumors classified as grade 1 and 18.4% of 114 tumors classified as grade 2 on the endometrial biopsy, respectively. Wait time was not associated with grade change (P>.05). Controlling for age, ethnicity, body habitus, medical comorbidities, CA 125 level, and stage, multivariable analysis revealed that wait time was not associated with survival outcomes (5-year overall survival rates, wait time 1-14, 15-42, 43-84, and 85 days or more; 62.5%, 93.6%, 95.2%, and 100%, respectively, P>.05); however, grade 1 to 3 on the hysterectomy specimen remained as an independent prognosticator associated with decreased survival (5-year overall survival rates, grade 1 to 3 compared with grade change 1 to 1, 82.1% compared with 98.5%, P=.01). Among grade 1 preoperative biopsies, grade 1 to 3 was significantly associated with nonobesity (P=.039) and advanced stage (P=.019). Wait time for surgical staging was not associated with decreased survival outcome in patients with type I endometrial cancer.

Endometrial changes from short-term therapy with CDB-4124, a selective progesterone receptor modulator.

PubMed

Ioffe, Olga B; Zaino, Richard J; Mutter, George L

2009-03-01

Selective progesterone receptor modulators are a class of drugs with progesterone antagonist activity that may confer therapeutic benefit for reproductive disorders in premenopausal women. Endometrial structure, which is dynamically controlled by circulating sex hormones, is likely to be perturbed by progesterone receptor modulators through their progesterone antagonist properties. We examined endometrial histology in 58 premenopausal women treated with the progesterone receptor modulator CDB-4124 (also known as Proellex) for endometriosis or uterine leiomyomata in two clinical trials. Endometrial biopsies obtained after 3 or 6 months with doses of 12.5, 25, or 50 mg daily oral CDB-4124 were reviewed independently by three pathologists. Consensus diagnoses using the World Health Organization hyperplasia scoring system, comments on specific histologic features, and clinical annotation were collected and analyzed. The majority of the endometrial biopsies (103 of 174 biopsies) contained histologic changes that are not seen during normal menstrual cycles. The histology of CDB-4124-treated patients was generally inactive or atrophic, and less frequently, proliferative or secretory, superimposed upon which were novel changes including formation of cystically dilated glands, and secretory changes coexisting with mitoses and apoptotic bodies. With increasing treatment dose and duration, the cysts became predominant and their lining inactive or atrophic. Cystic glands in the CDB-4124-treated subjects correlated with increased endometrial thickness by ultrasound. None of the CDB-4124-treated patients developed endometrial carcinoma or hyperplasia while on therapy. CDB-4124 therapy for 3-6 months produces histologic changes that are sufficiently novel that they might easily be misinterpreted by pathologists, particularly as disordered proliferative or hyperplastic endometrium. Knowledge of the constellation of endometrial changes associated with this agent and other progesterone receptor modulators, including cystic architecture and mixed non-physiologic epithelial changes will prevent misdiagnosis.

Prostaglandin receptor EP3 regulates cell proliferation and migration with impact on survival of endometrial cancer patients

PubMed Central

Zhu, Junyan; Trillsch, Fabian; Mayr, Doris; Kuhn, Christina; Rahmeh, Martina; Hofmann, Simone; Vogel, Marianne; Mahner, Sven; Jeschke, Udo; von Schönfeldt, Viktoria

2018-01-01

Background Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. Methods We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3. Results EP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells. Conclusions EP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy. PMID:29416671

Prostaglandin receptor EP3 regulates cell proliferation and migration with impact on survival of endometrial cancer patients.

PubMed

Zhu, Junyan; Trillsch, Fabian; Mayr, Doris; Kuhn, Christina; Rahmeh, Martina; Hofmann, Simone; Vogel, Marianne; Mahner, Sven; Jeschke, Udo; von Schönfeldt, Viktoria

2018-01-02

Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3. EP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells. EP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy.

GLUT-1 Expression in Proliferative Endometrium, Endometrial Hyperplasia, Endometrial Adenocarcinoma and the Relationship Between GLUT-1 Expression and Prognostic Parameters in Endometrial Adenocarcinoma.

PubMed

Canpolat, Tuba; Ersöz, Canan; Uğuz, Aysun; Vardar, Mehmet Ali; Altintaş, Aytekin

2016-01-01

Malignant cells show increased glucose uptake in in vitro and in vivo studies. This uptake is mediated by glucose transporter proteins. GLUT-1 is the most common transporter protein, and its expression is reported to be increase in many human cancers. The aim of this study is to determine the GLUT-1 overexpression in benign, hyperplastic, and malignant endometrial tissues, to evaluate the usefulness of GLUT-1 expression in endometrial hyperplasia, and to determine its role in the neoplastic progression to endometrioid type adenocarcinoma. We also aimed to analyze prognostic clinical parameters, predict prognosis, and survival. We examined immunohistochemical expression of GLUT-1 in 91 cases of endometrial hyperplasia, 100 cases of endometrioid type adenocarcinoma, and 10 proliferative endometrial tissues. The percentage of positive cells and staining intensity were assessed in a semi quantitative fashion and scored (1+ to 3+). GLUT-1 immunoreactivity was not present in proliferative endometrium. Twenty-nine (31.9%) of 91 endometrial hyperplasia cases showed positive immunoreactivity, of which only six were cases of hyperplasia without atypia while 23 of them were cases with atypia. We found GLUT-1 positivity of 95% in endometrioid type adenocarcinoma. GLUT-1 overexpression was not significantly correlated with any of the clinicopathological parameters except histological grade in endometrioid adenocarcinoma; the survival was not found to be correlated with GLUT-1 expression. GLUT-1 immunostaining may be useful in distinguishing hyperplasia without atypia from hyperplasia with atypia; GLUT-1 overexpression is a consistent feature of endometrioid adenocarcinoma. A correlation between GLUT -1 expression and tumor grade has been found, although other prognostic parameters and survival has no meaningful correlation.

Endometrial Adenocarcinoma Presenting as Hematometra with Underlying Thickened Endometrial Lining in a Postmenopausal Woman - A Case Report.

PubMed

Bacalbasa, Nicolae; Balescu, Irina; Dragan, Ioana; Banceanu, Gabriel; Suciu, Ioan; Suciu, Nicolae

2016-05-01

Although most postmenopausal women diagnosed with endometrial cancer usually present with vaginal bleeding, when complete cervical stenosis is present, this sign may be missing. In these cases, the patient usually complaints for pelvic or abdominal pain while the transvaginal ultrasonography might reveal the presence of an intrauterine fluid collection in association with a thickened endometrial lining. We present the case of a 65-year-old patient who presented with association of pelvic pain, enlarged uterine cavity with an underlying hematometra and an irregular, thickened endometrium who was submitted to surgery for total histerectomy, bilateral adnexectomy, pelvic and para-aortic lymph node dissection. Histopathological studies revealed the presence of a well-differentiated endometrial adenocarcinoma. At three years of follow-up, the patient is free of any recurrent disease. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

miR-200 Regulates Endometrial Development During Early Pregnancy

PubMed Central

Mainigi, Monica A.; Word, R. Ann; Kraus, W. Lee; Mendelson, Carole R.

2016-01-01

For successful embryo implantation, endometrial stromal cells must undergo functional and morphological changes, referred to as decidualization. However, the molecular mechanisms that regulate implantation and decidualization are not well defined. Here we demonstrate that the estradiol- and progesterone-regulated microRNA (miR)-200 family was markedly down-regulated in mouse endometrial stromal cells prior to implantation, whereas zinc finger E-box binding homeobox-1 and -2 and other known and predicted targets were up-regulated. Conversely, miR-200 was up-regulated during in vitro decidualization of human endometrial stromal cells. Knockdown of miR-200 negatively affected decidualization and prevented the mesenchymal-epithelial transition-like changes that accompanied decidual differentiation. Notably, superovulation of mice and humans altered miR-200 expression. Our findings suggest that hormonal alterations that accompany superovulation may negatively impact endometrial development and decidualization by causing aberrant miR-200 expression. PMID:27533790

Expression of placental protein 14 by the new endometrial cancer cell line MFE-280 in vitro and by endometrial carcinomas in vivo.

PubMed

Hackenberg, R; Loos, S; Nia, A H; Kunzmann, R; Schulz, K D

1998-01-01

MFE-280 endometrial cancer cells express PP14 (placental protein 14) in vitro. PP14 is normally found in the secretory endometrium and in placental tissue. MFE-280 cells, which are tumorigenic in nude mice, were derived from a recurrent, poorly differentiated endometrial carcinoma. The cells were initially grown in suspension culture and later transferred to monolayer cultures. Karyotyping revealed near-diploidy with a complex heterogeneous aberration pattern. MFE-280 cells were positive for the cytokeratins 7, 8, 18 and 19 as well as for vimentin. The expression of PP14 in MFE-280 cells was demonstrated by immunochemistry and reverse transcriptase--polymerase chain reaction. PP14-mRNA was also detected in one out of five endometrial cancer specimen. In tumor tissue the expression of PP14 was not dependent on progestins.

Endometrial Cancer and the Role of Lymphadenectomy.

PubMed

Clark, Leslie H; Soper, John T

2016-06-01

The role of lymph node dissection in early-stage endometrial cancer is highly debated, but staging and prognosis are dependent on knowledge of lymph node metastasis. We sought to review the available data on the use of lymph node assessment in presumed early-stage endometrial cancer. A comprehensive literature review was performed using MEDLINE, the Cochrane Collaborative Database, and PubMed. There is limited retrospective data that suggest a therapeutic benefit to lymphadenectomy. Prospective randomized trials have not shown a benefit to lymphadenectomy in low-risk patients, but found significant morbidity in patients undergoing lymphadenectomy. Selective lymph node assessment should be used in low-risk endometrial cancer. Sentinel lymph node assessment is emerging as a potential strategy for lymph node assessment. Selective use of lymphadenectomy in early-stage endometrial cancer can reduce the morbidity associated with lymph node dissection without compromising clinical outcomes. Multiple strategies are available including sentinel lymph nodes and risk factor based lymphadenectomy.

Potential of mid-infrared spectroscopy as a non-invasive diagnostic test in urine for endometrial or ovarian cancer.

PubMed

Paraskevaidi, Maria; Morais, Camilo L M; Lima, Kássio M G; Ashton, Katherine M; Stringfellow, Helen F; Martin-Hirsch, Pierre L; Martin, Francis L

2018-06-07

The current lack of an accurate, cost-effective and non-invasive test that would allow for screening and diagnosis of gynaecological carcinomas, such as endometrial and ovarian cancer, signals the necessity for alternative approaches. The potential of spectroscopic techniques in disease investigation and diagnosis has been previously demonstrated. Here, we used attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy to analyse urine samples from women with endometrial (n = 10) and ovarian cancer (n = 10), as well as from healthy individuals (n = 10). After applying multivariate analysis and classification algorithms, biomarkers of disease were pointed out and high levels of accuracy were achieved for both endometrial (95% sensitivity, 100% specificity; accuracy: 95%) and ovarian cancer (100% sensitivity, 96.3% specificity; accuracy 100%). The efficacy of this approach, in combination with the non-invasive method for urine collection, suggest a potential diagnostic tool for endometrial and ovarian cancers.

Does human endometrial LGR5 gene expression suggest the existence of another hormonally regulated epithelial stem cell niche?

PubMed

Tempest, N; Baker, A M; Wright, N A; Hapangama, D K

2018-06-01

Is human endometrial leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) gene expression limited to the postulated epithelial stem cell niche, stratum basalis glands, and is it hormonally regulated? LGR5 expressing cells are not limited to the postulated stem cell niche but LGR5 expression is hormonally regulated. The human endometrium is a highly regenerative tissue; however, endometrial epithelial stem cell markers are yet to be confirmed. LGR5 is a marker of stem cells in various epithelia. The study was conducted at a University Research Institute. Endometrial samples from 50 healthy women undergoing benign gynaecological surgery with no endometrial pathology at the Liverpool Women's hospital were included and analysed in the following six sub-categories; proliferative, secretory phases of menstrual cycle, postmenopausal, those using oral and local progestagens and samples for in vitro explant culture. In this study, we used the gold standard method, in situ hybridisation (ISH) along with qPCR and a systems biology approach to study the location of LGR5 gene expression in full thickness human endometrium and Fallopian tubes. The progesterone regulation of endometrial LGR5 was examined in vivo and in short-term cultured endometrial tissue explants in vitro. LGR5 expression was correlated with epithelial proliferation (Ki67), and expression of previously reported epithelia progenitor markers (SOX9 and SSEA-1) immunohistochemistry (IHC). LGR5 gene expression was significantly higher in the endometrial luminal epithelium than in all other epithelial compartments in the healthy human endometrium, including the endometrial stratum basalis (P < 0.05). The strongest SSEA-1 and SOX9 staining was observed in the stratum basalis glands, but the general trend of SOX9 and SSEA-1 expression followed the same cyclical pattern of expression as LGR5. Stratum functionalis epithelial Ki67-LI and LGR5 expression levels correlated significantly (r = 0.74, P = 0.01), however, they did not correlate in luminal and stratum basalis epithelium (r = 0.5 and 0.13, respectively). Endometrial LGR5 demonstrates a dynamic spatiotemporal expression pattern, suggesting hormonal regulation. Oral and local progestogens significantly reduced endometrial LGR5 mRNA levels compared with women not on hormonal treatment (P < 0.01). Our data were in agreement with in silico analysis of published endometrial microarrays. We did not generate our own large scale data but interrogated publically available large scale data sets. In the absence of reliable antibodies for human LGR5 protein and validated lineage markers for the various epithelial populations that potentially exist within the endometrium, our study does not formally characterise or examine the functional ability of the resident LGR5+ cells as multipotent. These data will facilitate future lineage tracing studies in the human endometrial epithelium; to identify the location of stem cells and further complement the in vitro functional studies, to confirm if the LGR5 expressing epithelial cells indeed represent the epithelial stem cell population. This work was supported by funding from the Wellbeing of Women project grant (RTF510) and Cancer Research UK (A14895). None of the authors have any conflicts of interest to disclose.

Effects of interferon-tau and steroids on cytochrome P450 activity in bovine endometrial epithelial cells

USDA-ARS?s Scientific Manuscript database

The objective of the current study was to examine cyclooxygenase (COX), cytochrome P450 1A (CYP1A) and 2C (CYP2C) activity in bovine endometrial cell cultures following exposure to oxytocin (OT), interferon-t (IFN), estradiol (E2) and/or progesterone (P4). Bovine endometrial epithelial cells were tr...

A prospective investigation of fish, meat and cooking-related carcinogens with endometrial cancer incidence.

PubMed

Arem, H; Gunter, M J; Cross, A J; Hollenbeck, A R; Sinha, R

2013-08-06

There are limited prospective studies of fish and meat intakes with risk of endometrial cancer and findings are inconsistent. We studied associations between fish and meat intakes and endometrial cancer incidence in the large, prospective National Institutes of Health-AARP Diet and Health Study. Intakes of meat mutagens 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP) were also calculated. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We observed no associations with endometrial cancer risk comparing the highest to lowest intake quintiles of red (HR=0.91, 95% CI 0.77-1.08), white (0.98, 0.83-1.17), processed meats (1.02, 0.86-1.21) and fish (1.10, 95% CI 0.93-1.29). We also found no associations between meat mutagen intakes and endometrial cancer. Our findings do not support an association between meat or fish intakes or meat mutagens and endometrial cancer.

Does probability guided hysteroscopy reduce costs in women investigated for postmenopausal bleeding?

PubMed

Breijer, M C; van Hanegem, N; Visser, N C M; Verheijen, R H M; Mol, B W J; Pijnenborg, J M A; Opmeer, B C; Timmermans, A

2015-01-01

To evaluate whether a model to predict a failed endometrial biopsy in women with postmenopausal bleeding (PMB) and a thickened endometrium can reduce costs without compromising diagnostic accuracy. Model based cost-minimization analysis. A decision analytic model was designed to compare two diagnostic strategies for women with PMB: (I) attempting office endometrial biopsy and performing outpatient hysteroscopy after failed biopsy and (II) predicted probability of a failed endometrial biopsy based on patient characteristics to guide the decision for endometrial biopsy or immediate hysteroscopy. Robustness of assumptions regarding costs was evaluated in sensitivity analyses. Costs for the different strategies. At different cut-offs for the predicted probability of failure of an endometrial biopsy, strategy I was generally less expensive than strategy II. The costs for strategy I were always € 460; the costs for strategy II varied between € 457 and € 475. At a 65% cut-off, a possible saving of € 3 per woman could be achieved. Individualizing the decision to perform an endometrial biopsy or immediate hysteroscopy in women presenting with postmenopausal bleeding based on patient characteristics does not increase the efficiency of the diagnostic work-up.

A prospective investigation of fish, meat and cooking-related carcinogens with endometrial cancer incidence

PubMed Central

Arem, H; Gunter, M J; Cross, A J; Hollenbeck, A R; Sinha, R

2013-01-01

Background: There are limited prospective studies of fish and meat intakes with risk of endometrial cancer and findings are inconsistent. Methods: We studied associations between fish and meat intakes and endometrial cancer incidence in the large, prospective National Institutes of Health-AARP Diet and Health Study. Intakes of meat mutagens 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP) were also calculated. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: We observed no associations with endometrial cancer risk comparing the highest to lowest intake quintiles of red (HR=0.91, 95% CI 0.77–1.08), white (0.98, 0.83–1.17), processed meats (1.02, 0.86–1.21) and fish (1.10, 95% CI 0.93–1.29). We also found no associations between meat mutagen intakes and endometrial cancer. Conclusion: Our findings do not support an association between meat or fish intakes or meat mutagens and endometrial cancer. PMID:23695021

Role of endometrial cancer abnormal MMR protein in screening Lynch-syndrome families.

PubMed

Long, Qiongxian; Peng, Yong; Tang, Zhirong; Wu, Cailiang

2014-01-01

To identify patients with endometrial cancer with potential Lynch-related DNA mismatch repair (MMR) protein expression defects and to explore the role of these defects in screening for LS. Endometrial cancers from 173 patients recruited to the Nanchong Central Hospital were tested for MMR (MLH1, MSH2, PMS2, and MSH6) protein expression using immunohistochemistry (IHC). In the 173 tumor tissue samples, the expression loss rates of MSH6, MSH2, PMS2 and MLH1 protein were 16.18% (28/173), 12.14% (21/173), 7.51% (13/173) and 5.78% (10/173), respectively. The total loss rate of MMR protein was 29.89% (27/87). There were 19 patients with a family history of cancer, of which 18 patients demonstrated loss of expression of MMR protein. In the 22 abnormal MMR patients without family history, five families were found to have Lynch-associated cancer (colorectal cancer, endometrial cancer, ovarian cancer, stomach cancer) after follow-up for two years. MMR proteins play an important role in the progress of endometrial cancer. The routine testing of MMR proteins in endometrial cancer can contribute to the screening of LS families, especially small families.

Suppression of IL-1beta-induced COX-2 expression by trichostatin A (TSA) in human endometrial stromal cells.

PubMed

Wu, Yan; Guo, Sun-Wei

2007-11-01

Over-production of cyclooxygenase-2 (COX-2) plays an important role in the positive feedback loop that leads to proliferation and inflammation in endometriosis. Following our observation that histone deacetylase inhibitors (HDACIs) trichostatin A (TSA) and valproic acid (VPA) can suppress proliferation of endometrial stromal cells, we sought to determine whether TSA suppresses IL-1beta-induced COX-2 expression in endometrial stromal cells. In vitro study using a recently established immortalized endometrial stromal cell line. The stromal cells were pretreated with TSA before stimulation with IL-1beta, and COX-2 gene and protein expression was measured by real-time quantitative RT-PCR and Western blot analysis, respectively. IL-1beta stimulated COX-2 expression in a concentration-dependent manner in endometrial stromal cells. The induced COX-2 gene and protein expression were suppressed by TSA pretreatment. TSA suppresses IL-1beta-induced COX-2 gene and protein expression in endometrial stromal cells. This finding, coupled with the findings that TSA and another HDACI, valproic acid, suppress proliferation and induce cell cycle arrest, suggests that HDACIs are a promising class of compound that has therapeutic potential for endometriosis.

[Semiquantitative measurement of progesterone receptors in luteal-phase-defect endometrial cells during secretory phase].

PubMed

Ma, Q; Han, Z; Huang, W

1998-03-01

To investigate the changes of endometrial progesterone receptor (PR) of luteal-phase-defect (LPD) patients during the secretory phase, thirteen patients with complaints of infertility or habitual abortion were studied. During the early-mid secretory phase, endometrial tissue was obtained by dilatation and curettage (D & C) for histological and receptor study: meanwhile serum E2, P, FSH, LH and PRL were measured. Based on histologic diagnosis, the patients were divided into two groups: the LPD group (n = 7) and the normal control group(n = 6). PR content was determined by immunohisto-chemical (IHC) assay. The results showed that during the early-mid luteal phase a significantly low PR content on endometrial glandular nucleus was observed in LPD group, compared with normal control(6.75 +/- 2.57 vs 9.50 +/- 1.64 P < 0.05), but no difference in serum progesterone was noted between the two groups. These findings suggest that during early-mid secretory phase, PR content on endometrial glandular nucleus decreases in LPD cases, which results in deficient response of endometrium to proper stimulus of progesterone. This change may cause endometrial secretory deficiency and blockade of embreyo implantation. That is why infertility or habitual abortion happened.

CTCF genetic alterations in endometrial carcinoma are pro-tumorigenic

PubMed Central

Marshall, A D; Bailey, C G; Champ, K; Vellozzi, M; O'Young, P; Metierre, C; Feng, Y; Thoeng, A; Richards, A M; Schmitz, U; Biro, M; Jayasinghe, R; Ding, L; Anderson, L; Mardis, E R; Rasko, J E J

2017-01-01

CTCF is a haploinsufficient tumour suppressor gene with diverse normal functions in genome structure and gene regulation. However the mechanism by which CTCF haploinsufficiency contributes to cancer development is not well understood. CTCF is frequently mutated in endometrial cancer. Here we show that most CTCF mutations effectively result in CTCF haploinsufficiency through nonsense-mediated decay of mutant transcripts, or loss-of-function missense mutation. Conversely, we identified a recurrent CTCF mutation K365T, which alters a DNA binding residue, and acts as a gain-of-function mutation enhancing cell survival. CTCF genetic deletion occurs predominantly in poor prognosis serous subtype tumours, and this genetic deletion is associated with poor overall survival. In addition, we have shown that CTCF haploinsufficiency also occurs in poor prognosis endometrial clear cell carcinomas and has some association with endometrial cancer relapse and metastasis. Using shRNA targeting CTCF to recapitulate CTCF haploinsufficiency, we have identified a novel role for CTCF in the regulation of cellular polarity of endometrial glandular epithelium. Overall, we have identified two novel pro-tumorigenic roles (promoting cell survival and altering cell polarity) for genetic alterations of CTCF in endometrial cancer. PMID:28319062

Endometrial adenocarcinoma arising in a Turner's syndrome patient with spontaneous menstruation: a case report.

PubMed

Sasamoto, Naoko; Ueda, Yutaka; Amemiya, Kyoka; Enomoto, Takayuki; Morii, Eiichi; Adachi, Kazushige

2014-01-01

Women with Turner's syndrome exhibit anovulation, and the majority do not spontaneously menstruate. We present an unusual case of endometrial adenocarcinoma developing in a Turner's syndrome patient who was exhibiting spontaneous menstruation while not receiving regular hormone therapy. The patient's karyotype from blood lymphocytes was a mosaic of 45,XO/ 46,XX. Menarche and sexual development were normal. Her menstrual cycle had been regular for one year, but then became noticeably irregular. At age 26 she was referred to our hospital after bleeding for almost 1 year. An endometrial adenocarcinoma was detected during performance of diagnostic endometrial curettage. A total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy was conducted. The final histological diagnosis was endometrial adenocarcinoma, Grade 1, pT1a N0 M0. Fluorescence in situ hybridization analysis of the right and left ovaries revealed a mosaic karyotype of 45,XO/ CONCLUSION: Previous reports regarding Turner's syndrome detected spontaneous menstruation in only 16% of patients; however, spontaneous menstruation was observed in 8 of 10 (80%) Turner's syndrome cases that developed endometrial carcinoma without receiving regular hormone therapy (p < 0.0001). Hormone therapy may be indicated for an irregular menstrual cycle in Turner's syndrome patients.

MicroRNA expression profiling in endometriosis-associated infertility and its relationship with endometrial receptivity evaluated by ultrasound.

PubMed

Xu, Xianfeng; Li, Zhenzhou; Liu, Jin; Yu, Sha; Wei, Zhaolian

2017-01-01

To investigate the microRNA expression profiling in endometriosis-associate infertility, and relationship between the microRNA expression and endometrial receptivity evaluated by ultrasound. First, miRNA expression profiling difference of ectopic endometrium between 8 endometriosis patients and 6 endometriosis-free patients were compared. Bioinformatics analyses detected 61 differentially expressed (DE) known miRNAs and 57 DE novel miRNAs. Next, other 24 patients were selected for checking the microRNAs in differential expression by RT-PCR. Among them, case and control groups include 14 endometriosis and 10 endometriosis-free infertility patients, respectively. Last, endometrial receptivity of other 20 endometriosis patients was evaluated by ultrasound. In this group of patients, 12 had high endometrial receptivity, in which infertility is caused by fallopian tube occlusion, and 8 had low endometrial receptivity. The study compared endometrial miRNAs expression between two groups, and also evaluated the relationship between the endometrial miRNAs expression and the endometrial receptivity. First, study indicated that "proteinaceous extracellular matrix," "laminin binding" and "extracellular matrix binding" were enriched in 6 up-regulated miRNA targets, while "cell proliferation" was enriched in the 4 down-regulated miRNA targets. Second, 10 miRNAs in different expression (miR-1304- 3p, miR-544b, miR-3684, miR-494-5p, miR-4683, miR-6747-3p; miR-3935, miR-4427, miR-652-5p, miR-205-5p) were detected by RT-PCR, and the results showed statistically significant differences between 2 groups in all 10 miRNAs. Third, the expression levels of miR-1304-3p, miR-494-5p, and miR-4427 were different between the two groups with different endometrial receptivity. But for the miR-544b, there was no statistically significant difference between two groups. The study provided a comprehensive understanding to the current knowledge in the field of miRNAs in endometriosis and the relationship between them and the endometrial receptivity. miRNAs could be used as diagnostic biomarkers and therapeutic agents for this disease. The combination of ultrasound and miRNAs detection could be a better choice for the diagnosis of infertility in the future.

A Common Variant at the 14q32 Endometrial Cancer Risk Locus Activates AKT1 through YY1 Binding.

PubMed

Painter, Jodie N; Kaufmann, Susanne; O'Mara, Tracy A; Hillman, Kristine M; Sivakumaran, Haran; Darabi, Hatef; Cheng, Timothy H T; Pearson, John; Kazakoff, Stephen; Waddell, Nicola; Hoivik, Erling A; Goode, Ellen L; Scott, Rodney J; Tomlinson, Ian; Dunning, Alison M; Easton, Douglas F; French, Juliet D; Salvesen, Helga B; Pollock, Pamela M; Thompson, Deborah J; Spurdle, Amanda B; Edwards, Stacey L

2016-06-02

A recent meta-analysis of multiple genome-wide association and follow-up endometrial cancer case-control datasets identified a novel genetic risk locus for this disease at chromosome 14q32.33. To prioritize the functional SNP(s) and target gene(s) at this locus, we employed an in silico fine-mapping approach using genotyped and imputed SNP data for 6,608 endometrial cancer cases and 37,925 controls of European ancestry. Association and functional analyses provide evidence that the best candidate causal SNP is rs2494737. Multiple experimental analyses show that SNP rs2494737 maps to a silencer element located within AKT1, a member of the PI3K/AKT/MTOR intracellular signaling pathway activated in endometrial tumors. The rs2494737 risk A allele creates a YY1 transcription factor-binding site and abrogates the silencer activity in luciferase assays, an effect mimicked by transfection of YY1 siRNA. Our findings suggest YY1 is a positive regulator of AKT1, mediating the stimulatory effects of rs2494737 increasing endometrial cancer risk. Identification of an endometrial cancer risk allele within a member of the PI3K/AKT signaling pathway, more commonly activated in tumors by somatic alterations, raises the possibility that well tolerated inhibitors targeting this pathway could be candidates for evaluation as chemopreventive agents in individuals at high risk of developing endometrial cancer. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Association of Genetic Markers in the BCL-2 Family of Apoptosis-Related Genes with Endometrial Cancer Risk in a Chinese Population

PubMed Central

Dorjgochoo, Tsogzolmaa; Xiang, Yong-Bing; Long, Jirong; Shi, Jiajun; Deming, Sandra; Xu, Wang-Hong; Cai, Hui; Cheng, Jiarong; Cai, Qiuyin; Zheng, Wei; Shu, Xiao-Ou

2013-01-01

Background In vitro studies have demonstrated the role of the BCL-2 family of genes in endometrial carcinogenesis. The role of genetic variants in BCL-2 genes and their interactions with non-genetic factors in the development of endometrial cancer has not been investigated in epidemiological studies. Patients and Methods We examined the relationship between BCL-2 gene family variants and endometrial cancer risk among 1,028 patients and 1,922 age-matched community controls from Shanghai, China. We also investigated possible interactions between genetic variants and established risk factors (demographic, lifestyle and clinical). Individuals were genotyped for 86 tagging single nucleotide polymorphisms (SNPs) in the BCL2, BAX, BAD and BAK1 genes. Results Significant associations with endometrial cancer risk were found for 9 SNPs in the BCL2 gene (P trend<0.05 for all). For SNPs rs17759659 and rs7243091 (minor allele for both: G), the associations were independent. The odds ratio was 1.27 (95% CI: 1.04–1.53) for women with AG genotype for the SNP rs17759659 and 1.82 (95% CI: 1.21–2.73) for women with the GG genotype for the SNP rs7243091. No interaction between these two SNPs and established non-genetic risk factors of endometrial cancer was noticed. Conclusion Genetic polymorphisms in the BCL2 gene may be associated with the risk of endometrial cancer in Chinese women. PMID:23637776

Surgical management of early endometrial cancer: an update and proposal of a therapeutic algorithm.

PubMed

Falcone, Francesca; Balbi, Giancarlo; Di Martino, Luca; Grauso, Flavio; Salzillo, Maria Elena; Messalli, Enrico Michelino

2014-07-26

In the last few years technical improvements have produced a dramatic shift from traditional open surgery towards a minimally invasive approach for the management of early endometrial cancer. Advancement in minimally invasive surgical approaches has allowed extensive staging procedures to be performed with significantly reduced patient morbidity. Debate is ongoing regarding the choice of a minimally invasive approach that has the most effective benefit for the patients, the surgeon, and the healthcare system as a whole. Surgical treatment of women with presumed early endometrial cancer should take into account the features of endometrial disease and the general surgical risk of the patient. Women with endometrial cancer are often aged, obese, and with cardiovascular and metabolic comorbidities that increase the risk of peri-operative complications, so it is important to tailor the extent and the radicalness of surgery in order to decrease morbidity and mortality potentially derivable from unnecessary procedures. In this regard women with negative nodes derive no benefit from unnecessary lymphadenectomy, but may develop short- and long-term morbidity related to this procedure. Preoperative and intraoperative techniques could be critical tools for tailoring the extent and the radicalness of surgery in the management of women with presumed early endometrial cancer. In this review we will discuss updates in surgical management of early endometrial cancer and also the role of preoperative and intraoperative evaluation of lymph node status in influencing surgical options, with the aim of proposing a management algorithm based on the literature and our experience.

Effect of ovarian endometrioma on uterine and ovarian blood flow in infertile women.

PubMed

El-Mazny, Akmal; Kamel, Ahmed; Ramadan, Wafaa; Gad-Allah, Sherine; Abdelaziz, Suzy; Hussein, Ahmed M

2016-01-01

Angiogenesis has been found to be among the most important factors in the pathogenesis of endometriosis. The formation of new blood vessels is critical for the survival of newly implanted endometriotic foci. The use of 3-D power Doppler allows for the demonstration of the dynamic vascular changes that occur during the process of in vitro fertilization (IVF). We aimed to evaluate the effect of ovarian endometrioma on uterine and ovarian blood flow in infertile women. In a case-control study at a university teaching hospital, 138 women with unilateral ovarian endometrioma scheduled for IVF were compared to 138 women with male-factor or unexplained infertility. In the mid-luteal (peri-implantation) phase of the cycle, endometrial thickness, uterine and ovarian artery pulsatility index and resistance index, endometrial and ovarian volume, 3-D power Doppler vascularization index (VI), flow index (FI), and vascularization FI (VFI) values were measured in both groups. There were no significant differences ( P >0.05) in endometrial thickness, uterine ovarian artery pulsatility index and resistance index, endometrial and ovarian volume, or VI, FI, and VFI between the two groups. Furthermore, the endometrial and ovarian Doppler indices were not influenced by endometrioma size. No significant differences were observed in the ovarian Doppler indices between endometrioma-containing ovaries and contralateral ovaries. Ovarian endometrioma is not associated with impaired endometrial and ovarian blood flows in infertile women scheduled for IVF, and it is not likely to affect endometrial receptivity or ovarian function through a vascular mechanism.

Surgical Management of Early Endometrial Cancer: An Update and Proposal of a Therapeutic Algorithm

PubMed Central

Falcone, Francesca; Balbi, Giancarlo; Di Martino, Luca; Grauso, Flavio; Salzillo, Maria Elena; Messalli, Enrico Michelino

2014-01-01

In the last few years technical improvements have produced a dramatic shift from traditional open surgery towards a minimally invasive approach for the management of early endometrial cancer. Advancement in minimally invasive surgical approaches has allowed extensive staging procedures to be performed with significantly reduced patient morbidity. Debate is ongoing regarding the choice of a minimally invasive approach that has the most effective benefit for the patients, the surgeon, and the healthcare system as a whole. Surgical treatment of women with presumed early endometrial cancer should take into account the features of endometrial disease and the general surgical risk of the patient. Women with endometrial cancer are often aged, obese, and with cardiovascular and metabolic comorbidities that increase the risk of peri-operative complications, so it is important to tailor the extent and the radicalness of surgery in order to decrease morbidity and mortality potentially derivable from unnecessary procedures. In this regard women with negative nodes derive no benefit from unnecessary lymphadenectomy, but may develop short- and long-term morbidity related to this procedure. Preoperative and intraoperative techniques could be critical tools for tailoring the extent and the radicalness of surgery in the management of women with presumed early endometrial cancer. In this review we will discuss updates in surgical management of early endometrial cancer and also the role of preoperative and intraoperative evaluation of lymph node status in influencing surgical options, with the aim of proposing a management algorithm based on the literature and our experience. PMID:25063051

High coffee consumption and different brewing methods in relation to postmenopausal endometrial cancer risk in the Norwegian women and cancer study: a population-based prospective study.

PubMed

Gavrilyuk, Oxana; Braaten, Tonje; Skeie, Guri; Weiderpass, Elisabete; Dumeaux, Vanessa; Lund, Eiliv

2014-03-25

Coffee and its compounds have been proposed to inhibit endometrial carcinogenesis. Studies in the Norwegian population can be especially interesting due to the high coffee consumption and increasing incidence of endometrial cancer in the country. A total of 97 926 postmenopausal Norwegian women from the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were included in the present analysis. We evaluated the general association between total coffee consumption and endometrial cancer risk as well as the possible impact of brewing method. Multivariate Cox regression analysis was used to estimate risks, and heterogeneity tests were performed to compare brewing methods. During an average of 10.9 years of follow-up, 462 incident endometrial cancer cases were identified. After multivariate adjustment, significant risk reduction was found among participants who drank ≥8 cups/day of coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79). However, we did not observe a significant dose-response relationship. No significant heterogeneity in risk was found when comparing filtered and boiled coffee brewing methods. A reduction in endometrial cancer risk was observed in subgroup analyses among participants who drank ≥8 cups/day and had a body mass index ≥25 kg/m2, and in current smokers. These data suggest that in this population with high coffee consumption, endometrial cancer risk decreases in women consuming ≥8 cups/day, independent of brewing method.

Resveratrol Inhibits Development of Experimental Endometriosis In Vivo and Reduces Endometrial Stromal Cell Invasiveness In Vitro1

PubMed Central

Bruner-Tran, Kaylon L.; Osteen, Kevin G.; Taylor, Hugh S.; Sokalska, Anna; Haines, Kaitlin; Duleba, Antoni J.

2010-01-01

Endometriosis is a common gynecologic disorder characterized by ectopic attachment and growth of endometrial tissues. Resveratrol is a natural polyphenol with antiproliferative and anti-inflammatory properties. Our objective was to study the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro. Human endometrial tissues were obtained from healthy donors. Endometriosis was established in oophorectomized nude mice by intraperitoneal injection of endometrial tissues. Mice were treated with 17β-estradiol (8 mg, silastic capsule implants) alone (n = 16) or with resveratrol (6 mg/mouse; n = 20) for 10–12 and 18–20 days beginning 1 day after tissue injection. Mice were killed and endometrial implants were evaluated. A Matrigel invasion assay was used to examine the effects of resveratrol on HES cells. We assessed number and size of endometriotic implants in vivo and Matrigel invasion in vitro. Resveratrol decreased the number of endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10–30 μM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis. PMID:20844278

Molecular characterization of PRM associated endometrial changes, PAEC, following mifepristone treatment.

PubMed

Berger, C; Boggavarapu, N; Norlin, E; Queckbörner, S; Hörnaeus, K; Falk, A; Engman, M; Ramström, M; Lalitkumar, P G L; Gemzell-Danielsson, K

2018-06-08

The progesterone receptor modulator (PRM) Mifepristone hold the potential to be developed for regular contraception. However, long-term treatment can cause thickening of the endometrium and PRM associated endometrial changes (PAEC). The objective of this study was to explore the molecular expression of endometrium displaying PAEC after mifepristone treatment, in order to understand the future implications of PAEC and safety of long-term use. Endometrial biopsies were obtained from pre-menopausal women following three months of continuous mifepristone treatment. The biopsies were evaluated regarding occurrence of PAEC and followed up by a comparative analysis of gene expression in PAEC endometrium (n=7) with endometrium not displaying PAEC (n=4). Methods used included microarray analysis, Ingenuity Pathway Analysis and real time PCR. Three genes relevant within endometrial function were upregulated with PAEC; THY1 (p=0.02), ADAM12 (p=0.04) and TN-C (p=0.04). The proliferation marker MKi67 was not altered (p=0.31). None of the differentially regulated genes were involved in the endometrial cancer-signaling pathway (based on IPA knowledge database). The genes altered in endometrium displaying PAEC after three months of mifepristone exposure are mainly involved in the structural architecture of tissue. PAEC features may be explained by the altered genes and their networks affecting tissue architecture although not involved in endometrial cancer signaling pathways and thus treatment with mifepristone at this dosage does not show any adverse effect at endometrial level. Copyright © 2018. Published by Elsevier Inc.

L1CAM expression in endometrial carcinomas: an ENITEC collaboration study.

PubMed

van der Putten, Louis Jm; Visser, Nicole Cm; van de Vijver, Koen; Santacana, Maria; Bronsert, Peter; Bulten, Johan; Hirschfeld, Marc; Colas, Eva; Gil-Moreno, Antonio; Garcia, Angel; Mancebo, Gemma; Alameda, Fransesc; Trovik, Jone; Kopperud, Reidun K; Huvila, Jutta; Schrauwen, Stefanie; Koskas, Martin; Walker, Francine; Weinberger, Vit; Minar, Lubos; Jandakova, Eva; Snijders, Marc Plm; van den Berg-van Erp, Saskia; Matias-Guiu, Xavier; Salvesen, Helga B; Amant, Frederic; Massuger, Leon Fag; Pijnenborg, Johanna Ma

2016-09-06

Identification of aggressive endometrioid endometrial carcinomas (EECs) and non-endometrioid carcinomas (NEECs) is essential to improve outcome. L1 cell adhesion molecule (L1CAM) expression is a strong prognostic marker in stage I EECs, but less is known about L1CAM expression in advanced-stage EECs and NEECs. This study analyses L1CAM expression in a clinically representative cohort of endometrial carcinomas. The expression of L1CAM was immunohistochemically determined in 1199 endometrial carcinomas, treated at one of the European Network for Individualized Treatment of Endometrial Cancer (ENITEC) centres. Staining was considered positive when >10% of the tumour cells expressed L1CAM. The association between L1CAM expression and several clincopathological characteristics and disease outcome was calculated. In all, L1CAM was expressed in 10% of the 935 stage I EECs, 18% of the 160 advanced stage EECs, and 75% of the 104 NEECs. The expression of L1CAM was associated with advanced stage, nodal involvement, high tumour grade, non-endometrioid histology, lymphovascular space invasion, and distant recurrences in all cases, and with reduced survival in the EECs, but not in the NEECs. The expression of L1CAM is a strong predictor of poor outcome in EECs, but not NEECs. It is strongly associated with non-endometrioid histology and distant spread, and could improve the postoperative selection of high-risk endometrial carcinomas. The value of L1CAM expression in the preoperative selection of high-risk endometrial carcinomas should be studied.

Association of microRNA-200c expression levels with clinicopathological factors and prognosis in endometrioid endometrial cancer.

PubMed

Wilczynski, Milosz; Danielska, Justyna; Domanska-Senderowska, Daria; Dzieniecka, Monika; Szymanska, Bozena; Malinowski, Andrzej

2018-05-01

MicroRNAs (miRNAs) are regulators of gene expression, which play an important role in many critical cellular processes including apoptosis, proliferation and cell differentiation. Aberrant miRNA expression has been reported in a variety of human malignancies. Therefore, miRNAs may be potentially used as cancer biomarkers. miRNA-200c, which is a member of the miRNA-200 family, might play an essential role in tumor progression. The purpose of this study was to evaluate the prognostic and clinical significance of miRNA-200c in women with endometrioid endometrial cancer. Total RNA extraction from 90 archival formalin-fixed paraffin-embedded tissue samples of endometri-oid endometrial cancer and 10 normal endometrium samples was performed. After cDNA synthesis, real-time polymerase chain reaction was conducted and relative expression of miRNA-200c was assessed. Then, miRNA-200c expression levels were evaluated with regard to clinicopathological characteristics. The expression levels of miRNA-200c were significantly increased in endometrioid endometrial cancer samples. Expression of miRNA-200c maintained at significantly higher levels in the early stage endometrioid endometrial cancer compared with more advanced stages. In the Kaplan-Meier analysis, lower levels of miRNA-200c expression were associated with inferior survival. Expression levels of miRNA-200c might be associated with clinicopathological factors and survival in endometrioid endometrial cancer. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Gynecological conditions and the risk of endometrial cancer.

PubMed

Rowlands, Ingrid J; Nagle, Christina M; Spurdle, Amanda B; Webb, Penelope M

2011-12-01

To examine the association between gynecological conditions (including uterine fibroids, endometriosis, pelvic inflammatory disease and infections of the tubes/womb), and risk of endometrial cancer overall and by histological subtype. Data came from a population-based, case-control study, which included 1399 women with endometrial cancer diagnosed between 2005 and 2007 and 1539 controls. Women provided detailed risk factor information via interview or self-completed questionnaire. Logistic regression was used to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between gynecological conditions and cancer. A self-reported history of uterine fibroids was associated with an increased risk of endometrial cancer (OR=1.39; 95% CI: 1.10-1.74). This association was reduced for women with body-mass index≥35kg/m(2) (OR=0.71; 95% CI: 0.37-1.37), and increased in groups normally thought to be at low risk including women with normal BMI (OR=1.66; 95% CI: 1.14-2.41) and premenopausal women (OR=1.82; 95% CI: 0.99-3.32). After excluding conditions diagnosed in the previous year, we found no association between endometrial cancer and endometriosis, pelvic inflammatory disease, infections of the tubes/womb. There was no evidence that risk varied by tumor subtype. Overall these results suggest that women with uterine fibroids are at increased risk of endometrial cancer, and that greater monitoring of premenopausal and normal weight women with fibroids may be important for the early detection of endometrial cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

Fertility drugs and endometrial cancer risk: results from an extended follow-up of a large infertility cohort.

PubMed

Brinton, Louise A; Westhoff, Carolyn L; Scoccia, Bert; Lamb, Emmet J; Trabert, Britton; Niwa, Shelley; Moghissi, Kamran S

2013-10-01

Do fertility drugs influence the subsequent risk of endometrial cancer in a manner that is independent of other risk predictors, such as parity? In this follow-up of a large cohort of women evaluated for infertility and for whom information was captured on fertility drugs, indications for usage and other risk factors that might influence cancer risk, we found no evidence for a substantial relationship between fertility drug use and endometrial cancer risk. Although the hormonal etiology of endometrial cancer has been well established, it remains unclear whether the use of fertility drugs has an influence on risk. Results regarding the effects of fertility drugs on endometrial cancer risk have been inconsistent, although several studies have shown some evidence for possible increases in risk. The relationship is of particular interest given that clomiphene, a commonly prescribed drug, is a selective estrogen receptor modulator, with chemical properties similar to tamoxifen, another drug linked to an increase in endometrial cancer risk. In a retrospective cohort of 12 193 women evaluated for infertility between 1965 and 1988 at five US sites, follow-up was pursued through 2010 via both passive as well as active (questionnaire) means. Among the 9832 subjects for whom follow-up was allowed and achieved, 259 346 at-risk person-years (i.e. prior to hysterectomy) were accrued, and 118 invasive endometrial cancers identified. Cox regression determined hazard ratios (HRs) and 95% confidence intervals (CIs) for fertility treatments adjusted for endometrial cancer risk factors and causes of infertility. Although we observed slight increases in endometrial cancer risk associated with clomiphene (HR = 1.39, 95% CI: 0.96-2.01) and the less commonly prescribed gonadotrophins (1.34, 0.76-2.37), there were no convincing relationships of risk with either cycles of use or cumulative exposures for either drug. A statistically significant risk associated with the use of clomiphene among women who began use at younger ages (<30) (1.93, 1.24-3.00) may have reflected indications for drug usage rather than the effect of the drug itself. Women who received clomiphene followed by gonadotrophins were at a non-significantly elevated risk (1.77, 0.98-3.19). Like most studies of endometrial cancer, we were limited by sample sizes, particularly for evaluating subgroup associations. We were also unable to follow all women and were not able to obtain complete risk factor information (including hysterectomy status) for the entire cohort. Although we found no support for a relationship between fertility drugs and endometrial cancer risk, the association should continue to be monitored given that our study population was still young and had not yet reached the age of peak endometrial cancer incidence. This project was supported in part by funds from the intramural research program of the National Cancer Institute, National Institutes of Health. None of the authors has any conflicting interests to declare.

2D phase tomography of biotissues: IV. Wavelet processing of phase tomograms of the background and precancerous endometrial states

NASA Astrophysics Data System (ADS)

Peresunko, A. P.; Zavadovskya, I. G.

2004-06-01

The paper deals with the studying of prognostic possibilities of determining the orientation structure of endometrial strome in the normal state and hiperplasia. The laser diagnostic of endometrial state is based on the principles of optical changes of laser radiation during its passing through the histological sample with the following investigation of its wavelet coefficients.

Estrogen Metabolism and Risk of Postmenopausal Endometrial and Ovarian Cancer: the B ∼ FIT Cohort.

PubMed

Dallal, Cher M; Lacey, James V; Pfeiffer, Ruth M; Bauer, Douglas C; Falk, Roni T; Buist, Diana S M; Cauley, Jane A; Hue, Trisha F; LaCroix, Andrea Z; Tice, Jeffrey A; Veenstra, Timothy D; Xu, Xia; Brinton, Louise A

2016-02-01

Estrogen metabolites may have different genotoxic and mitogenic properties yet their relationship with endometrial and ovarian cancer risk remains unclear. Within the Breast and Bone Follow-up to the Fracture Intervention Trial (B ∼ FIT, n = 15,595), we conducted a case-cohort study to evaluate 15 pre-diagnostic serum estrogens and estrogen metabolites with risk of incident endometrial and ovarian cancer among postmenopausal women not on hormone therapy. Participants included 66 endometrial and 67 ovarian cancer cases diagnosed during follow-up (∼ 10 years) and subcohorts of 346 and 416 women, respectively, after relevant exclusions. Serum concentrations were measured by liquid chromatography-tandem mass spectrometry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression. Exposures were categorized in tertiles (T) and analyzed individually, as metabolic pathways (C-2, -4, or -16) and as ratios to parent estrogens (estradiol, estrone). Estradiol was significantly associated with increased endometrial cancer risk (BMI-adjusted HRT3vsT1 = 4.09, 95% CI 1.70, 9.85; p trend = 0.003). 2-Hydroxyestrone and 16α-hydroxyestrone were not associated with endometrial risk after estradiol adjustment (2-OHE1:HRT3vsT1 = 1.97, 95% CI 0.78, 4.94; 16-OHE1:HRT3vsT1 = 1.50, 95% CI 0.65, 3.46; p trend = 0.16 and 0.36, respectively). Ratios of 2- and 4-pathway catechol-to-methylated estrogens remained positively associated with endometrial cancer after BMI or estradiol adjustment (2-pathway catechols-to-methylated: HRT3vsT1 = 4.02, 95% CI 1.60, 10.1; 4-pathway catechols-to-methylated: HRT3vsT1 = 4.59, 95% CI 1.64, 12.9; p trend = 0.002 for both). Estrogens and estrogen metabolites were not associated with ovarian cancer risk; however, larger studies are needed to better evaluate these relationships. Estrogen metabolism may be important in endometrial carcinogenesis, particularly with less extensive methylation of 2- or 4-pathway catechols associated with elevated endometrial cancer risk.

Optimal Order of Successive Office Hysteroscopy and Endometrial Biopsy for the Evaluation of Abnormal Uterine Bleeding: A Randomized Controlled Trial.

PubMed

Sarkar, Papri; Mikhail, Emad; Schickler, Robyn; Plosker, Shayne; Imudia, Anthony N

2017-09-01

To estimate the optimal order of office hysteroscopy and endometrial biopsy when performed successively for evaluation of abnormal uterine bleeding. Patients undergoing successive office hysteroscopy and endometrial biopsy were included in a single-blind, prospective, randomized trial. The primary outcome was to evaluate the effect of order of procedures on patients' pain score. Prespecified secondary outcomes include procedure duration, hysteroscopic visualization of the uterine cavity, endometrial sample adequacy, and number of attempts at biopsy. Pain scores were assessed using a visual analog scale from 0 to 10 and endometrial sample adequacy was determined from the histopathology report. Hysteroscopy images were recorded. Sample size of 34 per group (n=68) was determined to be adequate to detect a difference of 20% in visual analog scale score between hysteroscopy first (group A) and biopsy first (group B) at α of 0.05 and 80% power. Between October 2015 and January 2017, 78 women were randomized to group A (n=40) and group B (n=38). There was no difference in global pain perception [7 (0-10) vs 7 (0-10); P=.57, 95% CI 5.8-7.1]. Procedure duration [3 (1-9) vs 3 (2-10), P=.32, 95% CI 3.3-4.1] and endometrial sample adequacy (78.9% vs 75.7%, P=.74) were similar in both groups. Group A patients had better endometrial visualization (P<.001) than group B based on the hysteroscopic images: excellent (50% vs 7.9%), good (20% vs 34.2%), and fair (22.5% vs 44.7%); group B participants required fewer endometrial biopsy attempts at obtaining adequate tissue sample (two vs one; P<.001, 1.6-1.9). Patients having successive office hysteroscopy and endometrial biopsy for evaluation of abnormal uterine bleeding, the global pain perception, and time required are independent of the order in which procedures are performed. Performing hysteroscopy first ensures better image, whereas biopsy first yields adequate tissue sample with fewer attempts. ClinicalTrials.gov, NCT02472184.

Endometrial stromal sarcoma diagnosed after uterine morcellation in laparoscopic supracervical hysterectomy.

PubMed

Della Badia, Carl; Karini, Homa

2010-01-01

Endometrial stromal sarcoma is a rare uterine cancer with no reliable method for preoperative diagnosis. A 30-year-old parous woman underwent laparoscopic supracervical hysterectomy because of a leiomyoma. The uterus was removed from the abdominal cavity with an electric morcellator with a spinning blade. The pathology report revealed low-grade endometrial stromal sarcoma. Two months after the initial surgery, a second laparoscopic procedure was performed. The final pathology report confirmed low-grade endometrial stromal sarcoma involving the ovary, fallopian tube, and ovarian artery. It was concluded that morcellation of leiomyomas at laparoscopic supracervical hysterectomy may potentially increase metastasis if the tumor is a sarcoma. Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.

Endometrial cancer occurence five years after breast cancer in BRCA2 mutation patient

PubMed Central

Oh, Sang Eun; Kim, Soo Hyun; Kim, Mee Seon

2015-01-01

We recently experienced a case of endometrial cancer 5 years after the diagnosis of breast cancer in a patient with a mutation in the BRCA2 gene. A 55-year-old Korean woman who had a past history of breast cancer in her 50s underwent an operation for endometrial cancer. Final pathology confirmed stage Ia, and no adjuvant treatment was performed. After surgery, considering her history of sequential cancer occurrence, genetic counseling was offered. The result showed the BRCA2 variation of unknown significance mutation. This is the first case report of sequential cancers (endometrial and breast) in a patient with a BRCA2 mutation among a Korean population. PMID:25798433

Endometrial proteins: a reappraisal.

PubMed

Seppälä, M; Julkunen, M; Riittinen, L; Koistinen, R

1992-06-01

Uterine factors influence reproduction at the macro-anatomy level, and the effects of hormonal steroids on endometrial morphology are well recognized in the histopathological diagnosis of dysfunctional bleeding and infertility. During the past decade, attention has been paid to endometrial protein synthesis and secretion with respect to endocrine stimuli and implantation, and to the paracrine/autocrine effects of endometrial peptide growth factors, their binding proteins and other factors. The emphasis of this presentation is on protein secretion of the secretory endometrium, in which progesterone plays a pivotal role. Insulin-like growth factors have receptors on the endometrium, and IGF-binding proteins, stimulated by progesterone, modulate the effects of IGFs locally. Also other protein products of the secretory endometrium have been reviewed in this communication, with special emphasis on studies of a progesterone-associated endometrial protein which has many names in the literature, such as PEP, PP14, alpha 2-PEG and AUP. Extensive studies are ongoing in many laboratories to elucidate the regulation, function, interplay at tissue and cellular levels, and clinical significance of these proteins.

Antiprogestin-releasing intrauterine devices

PubMed Central

Nayak, NR; Slayden, OD; Mah, K; Chwalisz, K; Brenner, Robert M

2007-01-01

Intrauterine devices (IUDs) that release progestins are highly effective contraceptives, but they induce breakthrough bleeding that some women find unacceptable. Because progesterone (P) antagonists (AP) are known to suppress the endometrium, induce amenorrhea, and inhibit fertility, AP IUDs may provide an effective contraceptive that also controls endometrial bleeding. Here we assessed the effects of empty (blank) vs AP-releasing (ZK 230 211) IUDs on bleeding patterns and endometrial growth in ovariectomized, artificially cycled macaques. The AP IUDs (but not the blank controls) induced extended, frank menstruation when inserted during the late luteal phase, an indication of local AP action. Over time, endometrial glandular and arterial proliferation were inhibited, steroid receptors were elevated, spiral arteries showed degenerative changes, progesterone withdrawal bleeding was prevented and estradiol-dependent proliferation was suppressed by the AP IUDs. In sum, AP IUDs suppressed the effects of P on endometrial progestational development and blocked the effects of estradiol on endometrial proliferation as previously shown for systemic treatment with APs. Therefore, AP IUDs may provide novel contraceptive devices with minimal breakthrough bleeding. PMID:17531599

The role of miRNAs in endometrial cancer.

PubMed

Vasilatou, Diamantina; Sioulas, Vasileios D; Pappa, Vasiliki; Papageorgiou, Sotirios G; Vlahos, Nikolaos F

2015-01-01

miRNAs are small noncoding RNAs that regulate gene expression at the post-transcriptional level. Since their discovery, miRNAs have been associated with every cell function including malignant transformation and metastasis. Endometrial cancer is the most common gynecologic malignancy. However, improvement should be made in interobserver agreement on histological typing and individualized therapeutic approaches. This article summarizes the role of miRNAs in endometrial cancer pathogenesis and treatment.

Etiology and Effects of Ciomiphene on Cystic Endometrial Hyperplasia in the Miniature Pig

DTIC Science & Technology

1986-12-17

progesterone influences on the endometrium. Perhaps the presence of this imbalance over a prolonged period of time could lead to the development of...consequently this imbalance in the estrogenic and progestational influence on the endometrium over a prolonged period of time could lead to the development ...endometrial hyperplasia (CEH) has been attributed to a prolonged , unopposed estrogenic influence on the endometrium (Jones et al. 1981). Endometrial

Nimesulide, a COX-2 inhibitor, does not reduce lesion size or number in a nude mouse model of endometriosis.

PubMed

Hull, M L; Prentice, A; Wang, D Y; Butt, R P; Phillips, S C; Smith, S K; Charnock-Jones, D S

2005-02-01

Women with endometriosis have elevated levels of cyclooxygenase-2 (COX-2) in peritoneal macrophages and endometriotic tissue. Inhibition of COX-2 has been shown to reduce inflammation, angiogenesis and cellular proliferation. It may also downregulate aromatase activity in ectopic endometrial lesions. Ectopic endometrial establishment and growth are therefore likely to be suppressed in the presence of COX-2 inhibitors. We hypothesized that COX-2 inhibition would reduce the size and number of ectopic human endometrial lesions in a nude mouse model of endometriosis. The selective COX-2 inhibitor, nimesulide, was administered to estrogen-supplemented nude mice implanted with human endometrial tissue. Ten days after implantation, the number and size of ectopic endometrial lesions were evaluated and compared with lesions from a control group. Immunohistochemical assessment of vascular development and macrophage and myofibroblast infiltration in control and treated lesions was performed. There was no difference in the number or size of ectopic endometrial lesions in control and nimesulide-treated nude mice. Nimesulide did not induce a visually identifiable difference in blood vessel development or macrophage or myofibroblast infiltration in nude mouse explants. The hypothesized biological properties of COX-2 inhibition did not influence lesion number or size in the nude mouse model of endometriosis.

Cancerous 'floater': a lesson learned about tissue identity testing, endometrial cancer and microsatellite instability.

PubMed

Bossuyt, Veerle; Buza, Natalia; Ngo, Nhu T; Much, Melissa A; Asis, Maria C; Schwartz, Peter E; Hui, Pei

2013-09-01

A 46-year-old woman presented with endometrial cells on a pap smear and underwent endometrial curettage. The specimen revealed secretory endometrium and a possible endometrial polyp. In addition, a single 4 mm fragment of well-differentiated adenocarcinoma was found. Tissue identity DNA genotyping was performed and the adenocarcinoma tissue fragment showed a drastically different allelic pattern from that of the background endometrium. To confirm tissue contamination, genotyping of three other tumor specimens-probable sources for a contaminant-was performed but failed to identify a match. Without confirmation of contamination, a second endometrial curettage was obtained from the patient, in which similar adenocarcinoma tissue was once again found. Further workup demonstrated that the patient had a microsatellite unstable (MSI) endometrial adenocarcinoma by immunohistochemistry and molecular testing. The patient subsequently underwent staging surgery, which revealed an early-stage, well-differentiated endometrioid adenocarcinoma. This case study illustrates an uncommon, yet important caveat of tissue identity testing by DNA genotyping, where MSI instability can significantly alter the allelic pattern of DNA polymorphisms in the tumor genome, leading to erroneous conclusion regarding the tissue identity. Awareness of this phenomenon is crucial for a molecular pathologist to avoid interpretation errors of tissue identity testing in a cancer diagnostic workup.

[Endometrial hyperplasia, diagnosis. Clinical, paraclinical exam and management].

PubMed

Pangal, Alexandra; Costăchescu, Gh; Aldea, Marie Jeanne

2010-01-01

Factors associated with unopposed estrogenic stimulation such as obesity, exogenous hormone use endometrial hyperplasia are related to the development of the most common form of endometrial carcinoma, that is, the endometroid subtype. We selected a group of patients diagnosed with endometrial hyperplasia by endometrial biopsy and histopathological examination. The main complaint in all cases was abnormal uterine bleeding. All patients had gynecological examination, vaginal ultrasound, hysteroscopy endometrial biopsy or D&C. 32 patients had also immunohistochemical staining for Ki67, EGF, ER, PGR. Cases with ages between 24-67 years were classified as: 100 simple hyperplasia, 10 complex hyperplasia, 43 atypical simple hyperplasia, 7 atypical complex hyperplasia. PR were 40-60% at all forms of hyperplasia, E2R were 30-40% in simple hyperplasia without atypia and 50-70% in complex hyperplasia without atypia. Correlation between immunohistochemical expression of E2R, PGR, Ki-67, EGF and body mass revealed an high immunohistochemical expression of E2R and Ki-67 in patients with hyperplasia without atypia and a low expression and high reactivity of EGF in cases with high body mass. Vaginal ultrasound and hysteroscopy are efficacious completion for histopathological diagnosis. We recommend an age/risk appropriate screening to detect risk factors and early disease in the asymptomatic patients.

Correlation of changes of (non)exfoliated endometrial organelles and expressions of Musashi-1 and β-catenin with endometriosis in menstrual period.

PubMed

Yu, Cong-Xiang; Song, Jing-Hui; Liang, Lei

2014-01-01

This study aims to investigate the correlation of structural changes of endometrial organelles and expressions of Musashi-1 (Msi-1) and β-catenin with the endometriosis (EMs) in the menstrual period. The structural changes of exfoliated and nonexfoliated endometrial organelles in the experimental group and the control group were observed by the transmission electron microscopy (TEM) on the first and fifth day of menstruation. (1) TEM: compared with the control group, the exfoliated endometrial organelles in the experimental group on the first day were rich, with irregular nucleus, the bi-nucleolus could be seen, with rich chromatin; while the shapes of epithelial secretory cells in the nonexfoliated endometrial gland were irregular, with abundant organelles, the basal film varied in width, with abnormal curvature, and a lot of intercellular collagen fibers could be seen. (2) The expressions of Msi-1 and β-catenin in the exfoliated and nonexfoliated endometrium of the experimental group were higher than those of the control group and exhibited positively correlation, while no correlation could be found within the control group. (1) The organelles' structural changes might cause the changes of endometrial cellular functions. (2) Msi-1 might participate in the formation of EMs through activating the Wnt/β-catenin signaling pathway.

Recombinant HE4 protein promotes proliferation of pancreatic and endometrial cancer cell lines.

PubMed

Lu, Qinsheng; Chen, Haibin; Senkowski, Christopher; Wang, Jianhao; Wang, Xue; Brower, Steven; Glasgow, Wayne; Byck, David; Jiang, Shi-Wen; Li, Jinping

2016-01-01

Pancreatic adenocarcinoma is one of the most deadly malignancies, and endometrial cancer represents the most common gynecologic cancer in the USA. Better understanding on the pathologic mechanisms and pathways is required for effective treatment of these malignancies. Recently, human epididymis protein 4 (HE4 or WFDC2), a secretory glycoprotein, was found to be overexpressed in pancreatic and endometrial cancers. In addition, studies have shown that HE4 overexpression in endometrial cancer cell lines led to faster cancer progression in a mouse subcutaneous model. These findings raise a question on the role(s) of secretory, extracellular HE4 in cancer development. In the present study, we found that treatment of pancreatic and endometrial cancer cell lines with purified, extracellular HE4 protein led to a significant increase in cell viability and proliferation. Moreover, extracellular HE4 protein was able to increase DNA synthesis, and modulate the mRNA and protein levels of cell cycle marker PCNA and cell cycle inhibitor p21. These effects appeared to be robust and sustainable and required a relatively low concentration of HE4 protein. The findings indicated the secreted, extracellular HE4 may carry some physiopathological functions. Via paracrine/endocrine actions, circulatory HE4 produced by malignant cells may contribute to pancreatic and endometrial cancer progression and/or metastasis.

Comparison of pregnancy rates between patients with and without local endometrial scratching before intrauterine insemination.

PubMed

Senocak, G C; Yapca, O E; Borekci, B

2017-11-01

To determine the implantation success of local endometrial injury in patients undergoing intrauterine insemination following ovulation induction with gonadotropins as an infertility treatment. In this prospective randomized controlled trial, ovulation induction was performed with gonadotropins in 80 patients following intrauterine insemination. In 40 patients, local endometrial injury (scratch) was performed in the midluteal phase of the cycle preceding ovarian stimulation with a Novak curette to the posterior side of the endometrial cavity. Fifteen pregnancies (37.5%) and 11 clinical pregnancies (27.5%) occurred in the intervention group, whereas eight pregnancies (20%) and five clinical pregnancies (12.5%) occurred in the control group. Although the pregnancy rates and clinical pregnancy rates were increased in the intervention group, no statistically significant difference was found between the intervention and control groups (pregnancy rates: P=0.084; clinical pregnancy rates: P=0.094). Performing local endometrial injury (scratch) in the cycle preceding ovulation induction in patients with a diagnosis of infertility and indication for intrauterine insemination increased the pregnancy and clinical pregnancy rates. This increase was not, however, statistically significant. More randomized, controlled, prospective studies with larger patient numbers are required before the use of iatrogenic induction of local endometrial injury can be recommended in routine clinical practice. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Long-term and baseline recreational physical activity and risk of endometrial cancer: the California Teachers Study.

PubMed

Dieli-Conwright, C M; Ma, H; Lacey, J V; Henderson, K D; Neuhausen, S; Horn-Ross, P L; Deapen, D; Sullivan-Halley, J; Bernstein, L

2013-08-06

Physical activity may be associated with decreasing endometrial cancer risk; it remains unclear whether the association is modified by body size. Among 93 888 eligible California Teachers Study participants, 976 were diagnosed with incident endometrial cancer between 1995-1996 and 2007. Cox proportional hazards regression methods were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for endometrial cancer associated with long-term (high school through age 54 years) and baseline (3 years prior to joining the cohort) strenuous and moderate recreational physical activity, overall and by body size. Increased baseline strenuous recreational physical activity was associated with decreased endometrial cancer risk (Ptrend=0.006) with approximately 25% lower risk among women exercising >3 h per week per year than among those exercising <1/2 h per week per year (RR, 0.76; 95% CI, 0.63-0.92). This inverse association was observed among overweight/obese women (body mass index ≥25 kg m(-2); Ptrend=0.006), but not among thinner women (Ptrend=0.12). Baseline moderate activity was associated with lower risk among overweight/obese women. Increasing physical activity, particularly strenuous activity, may be a lifestyle change that overweight and obese women can implement to reduce their endometrial cancer risk.

The effects of lauromacrogol injection into rat endometrial cysts: a preliminary experimental study.

PubMed

Liu, Wei; Wang, LongXia; Guo, Cui-Xia

2016-09-01

To determine the effectiveness of different concentrations of lauromacrogol injections for the treatment of endometriosis in an experimental animal model and to provide an experimental basis for a pre-clinical application of the drug. After autologous transplantation of endometrial tissue, 40 endometrial cysts were successfully established and randomly divided into three groups: a 1 % lauromacrogol injection group, a 0.5 % lauromacrogol injection group, and cysts without intervention (control group). We measured the changes in the volumes of the cysts in each group. We then compared the volumes of the endometrial implants before and after treatment and between the different groups and examined the histological findings. A significant difference in the spherical volume was found between the 1 % lauromacrogol injection group (P < 0.05). No significant difference was observed between the volume of the endometrial implants in the 0.5 % lauromacrogol injection group (P > 0.05). Regarding the histopathological observations, in the 1 % lauromacrogol injection group, the epithelia of the cystic implants had atrophied, and the glands had atrophied and were reduced in number. The surrounding stromal tissue had become loose and edematous. A 1 % lauromacrogol injection produced significant regression of the endometrial foci compared with a 0.5 % lauromacrogol injection or no treatment in a rat model of endometriosis.

CYP19A1 fine-mapping and Mendelian randomization: estradiol is causal for endometrial cancer

PubMed Central

Thompson, Deborah J; O'Mara, Tracy A; Glubb, Dylan M; Painter, Jodie N; Cheng, Timothy; Folkerd, Elizabeth; Doody, Deborah; Dennis, Joe; Webb, Penelope M; Gorman, Maggie; Martin, Lynn; Hodgson, Shirley; Michailidou, Kyriaki; Tyrer, Jonathan P; Maranian, Mel J; Hall, Per; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Ekici, Arif B; Dörk, Thilo; Hillemanns, Peter; Dürst, Matthias; Runnebaum, Ingo; Zhao, Hui; Depreeuw, Jeroen; Schrauwen, Stefanie; Amant, Frederic; Goode, Ellen L; Fridley, Brooke L; Dowdy, Sean C; Winham, Stacey J; Salvesen, Helga B; Trovik, Jone; Njolstad, Tormund S; Werner, Henrica M J; Ashton, Katie; Proietto, Tony; Otton, Geoffrey; Carvajal-Carmona, Luis; Tham, Emma; Liu, Tao; Mints, Miriam; Scott, Rodney J; McEvoy, Mark; Attia, John; Holliday, Elizabeth G; Montgomery, Grant W; Martin, Nicholas G; Nyholt, Dale R; Henders, Anjali K; Hopper, John L; Traficante, Nadia; Ruebner, Matthias; Swerdlow, Anthony J; Burwinkel, Barbara; Brenner, Hermann; Meindl, Alfons; Brauch, Hiltrud; Lindblom, Annika; Lambrechts, Diether; Chang-Claude, Jenny; Couch, Fergus J; Giles, Graham G; Kristensen, Vessela N; Cox, Angela; Bolla, Manjeet K; Wang, Qin; Bojesen, Stig E; Shah, Mitul; Luben, Robert; Khaw, Kay-Tee; Pharoah, Paul D P; Dunning, Alison M; Tomlinson, Ian; Dowsett, Mitch; Easton, Douglas F; Spurdle, Amanda B

2016-01-01

Candidate gene studies have reported CYP19A1 variants to be associated with endometrial cancer and with estradiol (E2) concentrations. We analyzed 2937 single nucleotide polymorphisms (SNPs) in 6608 endometrial cancer cases and 37 925 controls and report the first genome wide-significant association between endometrial cancer and a CYP19A1 SNP (rs727479 in intron 2, P=4.8×10−11). SNP rs727479 was also among those most strongly associated with circulating E2 concentrations in 2767 post-menopausal controls (P=7.4×10−8). The observed endometrial cancer odds ratio per rs727479 A-allele (1.15, CI=1.11–1.21) is compatible with that predicted by the observed effect on E2 concentrations (1.09, CI=1.03–1.21), consistent with the hypothesis that endometrial cancer risk is driven by E2. From 28 candidate-causal SNPs, 12 co-located with three putative gene-regulatory elements and their risk alleles associated with higher CYP19A1 expression in bioinformatical analyses. For both phenotypes, the associations with rs727479 were stronger among women with a higher BMI (Pinteraction=0.034 and 0.066 respectively), suggesting a biologically plausible gene-environment interaction. PMID:26574572

The significance of markers in the diagnosis of endometrial cancer

PubMed Central

Żyła, Monika M.; Wilczyński, Jacek R.; Kostrzewa, Marta; Księżakowska-Łakoma, Kinga; Nowak, Marek; Stachowiak, Grzegorz; Szyłło, Krzysztof

2016-01-01

Endometrial cancer is one of the most common cancers experienced by women throughout the world. It is also the most common malignancy within the female reproductive system, representing 37.7% of all disorders. The incidence increases with age, and is diagnosed most frequently in women between 45 and 65 years old. In the last few years, numerous studies have been performed to identify tumour biomarkers. Biomarkers include not only protein routinely used as tumour markers but also genes and chromosomes. The limiting factor in the use of markers in the diagnosis of endometrial cancer is their lack of specificity. However, specific markers for endometrial cancer are the subject of much research attention. Although moderately elevated levels of markers are present in a number of inflammatory or non-malignant diseases, significantly increased levels of markers indicate the development of cancer. Recently, research has been focused on the identification of molecular changes leading to different histological subtypes of endometrial cancer. In this paper the authors reviewed several currently investigated markers. Progress in these investigations is very important in the diagnostics and treatment of endometrial cancer. In particular, the identification of novel mutations and molecular profiles should enhance our ability to personalise adjuvant treatment with genome-guided targeted therapy. PMID:27980530

ROS are critical for endometrial breakdown via NF-κB-COX-2 signaling in a female mouse menstrual-like model.

PubMed

Wu, Bin; Chen, Xihua; He, Bin; Liu, Shuyan; Li, Yunfeng; Wang, Qianxing; Gao, Haijun; Wang, Shufang; Liu, Jianbing; Zhang, Shucheng; Xu, Xiangbo; Wang, Jiedong

2014-09-01

Progesterone withdrawal triggers endometrial breakdown and shedding during menstruation. Menstruation results from inflammatory responses; however, the role of reactive oxygen species (ROS) in menstruation remains unclear. In this study, we explored the role of ROS in endometrial breakdown and shedding. We found that ROS levels were significantly increased before endometrial breakdown in a mouse menstrual-like model. Vaginal smear inspection, morphology of uterine horns, and endometrial histology examination showed that a broad range of ROS scavengers significantly inhibited endometrial breakdown in this model. Furthermore, Western blot and immunohistochemical analysis showed that the intracellular translocation of p50 and p65 from the cytoplasm into the nucleus was blocked by ROS scavengers and real-time PCR showed that cyclooxygenase-2 (COX-2) mRNA expression was decreased by ROS scavengers. Similar changes also occurred in human stromal cells in vitro. Furthermore, Western blotting and real-time PCR showed that one ROS, hydrogen peroxide (H2O2), promoted translocation of p50 and p65 from the cytoplasm to the nucleus and increased COX-2 mRNA expression along with progesterone maintenance. The nuclear factor κB inhibitor MG132 reduced the occurrence of these changes in human stromal cells in vitro. Viewed as a whole, our results provide evidence that certain ROS are important for endometrial breakdown and shedding in a mouse menstrual-like model and function at least partially via nuclear factor-κB/COX-2 signaling. Similar changes observed in human stromal cells could also implicate ROS as important mediators of human menstruation.

Gene Expression Analysis of Early Stage Endometrial Cancers Reveals Unique Transcripts Associated with Grade and Histology but Not Depth of Invasion

PubMed Central

Risinger, John I.; Allard, Jay; Chandran, Uma; Day, Roger; Chandramouli, Gadisetti V. R.; Miller, Caela; Zahn, Christopher; Oliver, Julie; Litzi, Tracy; Marcus, Charlotte; Dubil, Elizabeth; Byrd, Kevin; Cassablanca, Yovanni; Becich, Michael; Berchuck, Andrew; Darcy, Kathleen M.; Hamilton, Chad A.; Conrads, Thomas P.; Maxwell, G. Larry

2013-01-01

Endometrial cancer is the most common gynecologic malignancy in the United States but it remains poorly understood at the molecular level. This investigation was conducted to specifically assess whether gene expression changes underlie the clinical and pathologic factors traditionally used for determining treatment regimens in women with stage I endometrial cancer. These include the effect of tumor grade, depth of myometrial invasion and histotype. We utilized oligonucleotide microarrays to assess the transcript expression profile in epithelial glandular cells laser microdissected from 79 endometrioid and 12 serous stage I endometrial cancers with a heterogeneous distribution of grade and depth of myometrial invasion, along with 12 normal post-menopausal endometrial samples. Unsupervised multidimensional scaling analyses revealed that serous and endometrioid stage I cancers have similar transcript expression patterns when compared to normal controls where 900 transcripts were identified to be differentially expressed by at least fourfold (univariate t-test, p < 0.001) between the cancers and normal endometrium. This analysis also identified transcript expression differences between serous and endometrioid cancers and tumor grade, but no apparent differences were identified as a function of depth of myometrial invasion. Four genes were validated by quantitative PCR on an independent set of cancer and normal endometrium samples. These findings indicate that unique gene expression profiles are associated with histologic type and grade, but not myometrial invasion among early stage endometrial cancers. These data provide a comprehensive perspective on the molecular alterations associated with stage I endometrial cancer, particularly those subtypes that have the worst prognosis. PMID:23785665

High coffee consumption and different brewing methods in relation to postmenopausal endometrial cancer risk in the Norwegian Women and Cancer Study: a population-based prospective study

PubMed Central

2014-01-01

Background Coffee and its compounds have been proposed to inhibit endometrial carcinogenesis. Studies in the Norwegian population can be especially interesting due to the high coffee consumption and increasing incidence of endometrial cancer in the country. Methods A total of 97 926 postmenopausal Norwegian women from the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were included in the present analysis. We evaluated the general association between total coffee consumption and endometrial cancer risk as well as the possible impact of brewing method. Multivariate Cox regression analysis was used to estimate risks, and heterogeneity tests were performed to compare brewing methods. Results During an average of 10.9 years of follow-up, 462 incident endometrial cancer cases were identified. After multivariate adjustment, significant risk reduction was found among participants who drank ≥8 cups/day of coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79). However, we did not observe a significant dose-response relationship. No significant heterogeneity in risk was found when comparing filtered and boiled coffee brewing methods. A reduction in endometrial cancer risk was observed in subgroup analyses among participants who drank ≥8 cups/day and had a body mass index ≥25 kg/m2, and in current smokers. Conclusions These data suggest that in this population with high coffee consumption, endometrial cancer risk decreases in women consuming ≥8 cups/day, independent of brewing method. PMID:24666820

Androgens regulate scarless repair of the endometrial "wound" in a mouse model of menstruation.

PubMed

Cousins, Fiona L; Kirkwood, Phoebe M; Murray, Alison A; Collins, Frances; Gibson, Douglas A; Saunders, Philippa T K

2016-08-01

The human endometrium undergoes regular cycles of synchronous tissue shedding (wounding) and repair that occur during menstruation before estrogen-dependent regeneration. Endometrial repair is normally both rapid and scarless. Androgens regulate cutaneous wound healing, but their role in endometrial repair is unknown. We used a murine model of simulated menses; mice were treated with a single dose of the nonaromatizable androgen dihydrotestosterone (DHT; 200 µg/mouse) to coincide with initiation of tissue breakdown. DHT altered the duration of vaginal bleeding and delayed restoration of the luminal epithelium. Analysis of uterine mRNAs 24 h after administration of DHT identified significant changes in metalloproteinases (Mmp3 and -9; P < 0.01), a snail family member (Snai3; P < 0.001), and osteopontin (Spp1; P < 0.001). Chromatin immunoprecipitation analysis identified putative androgen receptor (AR) binding sites in the proximal promoters of Mmp9, Snai3, and Spp1. Striking spatial and temporal changes in immunoexpression of matrix metalloproteinase (MMP) 3/9 and caspase 3 were detected after DHT treatment. These data represent a paradigm shift in our understanding of the role of androgens in endometrial repair and suggest that androgens may have direct impacts on endometrial tissue integrity. These studies provide evidence that the AR is a potential target for drug therapy to treat conditions associated with aberrant endometrial repair processes.-Cousins, F. L., Kirkwood, P. M., Murray, A. A., Collins, F., Gibson, D. A., Saunders, P. T. K. Androgens regulate scarless repair of the endometrial "wound" in a mouse model of menstruation. © The Author(s).

Interaction of soy food and tea consumption with CYP19A1 genetic polymorphisms in the development of endometrial cancer.

PubMed

Xu, Wang Hong; Dai, Qi; Xiang, Yong Bing; Long, Ji Rong; Ruan, Zhi Xian; Cheng, Jia Rong; Zheng, Wei; Shu, Xiao Ou

2007-12-15

Certain polyphenols inhibit the activity of aromatase, a critical enzyme in estrogen synthesis that is coded by the CYP19A1 gene. Consumption of polyphenol-rich foods and beverages, thus, may interact with CYP19A1 genetic polymorphisms in the development of endometrial cancer. The authors tested this hypothesis in the Shanghai Endometrial Cancer Study (1997-2003), a population-based case-control study of 1,204 endometrial cancer cases and 1,212 controls. Dietary information was obtained by use of a validated food frequency questionnaire. Genotypes of CYP19A1 at rs28566535, rs1065779, rs752760, rs700519, and rs1870050 were available for 1,042 cases and 1,035 controls. Unconditional logistic regression models were used to calculate odds ratios and their 95% confidence intervals after adjustment for potential confounding factors. Higher intake of soy foods and tea consumption were both inversely associated with the risk of endometrial cancer, with odds ratios of 0.8 (95% confidence interval: 0.6, 1.0) for the highest versus the lowest tertiles of intake of soy and 0.8 (95% confidence interval: 06, 0.9) for ever tea consumption. The association of single nucleotide polymorphisms rs1065779, rs752760, and rs1870050 with endometrial cancer was modified by tea consumption (p(interaction) < 0.05) but not by soy isoflavone intake. The authors' findings suggest that tea polyphenols may modify the effect of CYP19A1 genetic polymorphisms on the development of endometrial cancer.

Benzotriazole Enhances Cell Invasive Potency in Endometrial Carcinoma Through CTBP1-Mediated Epithelial-Mesenchymal Transition.

PubMed

Wang, Yiquan; Dai, Chencheng; Zhou, Cheng; Li, Wenqu; Qian, Yujia; Wen, Juan; Wang, Yang; Han, Bing; Ma, Jingjing; Xu, Juan; Fu, Ziyi; Ruan, Hongjie; Tong, Hua; Jia, Xuemei

2017-01-01

Benzotriazole (BTR) and its derivatives, such as intermediates and UV stabilizers, are important man-made organic chemicals found in everyday life that have been recently identified as environmental toxins and a threat to female reproductive health. Previous studies have shown that BTR could act as a carcinogen by mimicking estrogen. Environmental estrogen mimics could promote the initiation and development of female cancers, such as endometrial carcinoma, a type of estrogenic-sensitive malignancy. However, there is little information on the relationship between BTR and endometrial carcinoma. In this study, we aimed to demonstrate the biological function of BTR in endometrial carcinoma and explored the underlying mechanism. The CCK-8 assay was performed to detect cell viability; transwell-filter assay was used to assess cell invasion; gene microarray analysis was employed to determine gene expression patterns in response to BTR treatment; western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were carried out to detect the expression levels of BTR-related genes. Our data showed that BTR could induce the invasion and migration of endometrial carcinoma cells (Ishikawa and HEC-1-B). In addition, BTR increased the expression level of CTBP1, which could enhance the epithelial-mesenchymal transition (EMT) in cancer cells. Moreover, CTBP1 silencing reversed the effect of BTR on EMT progression in endometrial carcinoma cells. This study indicates that BTR could act as a carcinogen to promote the development of endometrial carcinoma mainly through CTBP1-mediated EMT, which deserves more attention. © 2017 The Author(s). Published by S. Karger AG, Basel.

Gonadal steroids regulate the expression of aggrecanases in human endometrial stromal cells in vitro

PubMed Central

Wen, Jiadi; Zhu, Hua; Leung, Peter CK

2013-01-01

The human endometrium undergoes cyclic change during each menstrual cycle in response to gonadal steroids. Proteolysis of endometrial extracellular matrix (ECM) is necessary to prepare this dynamic tissue for pregnancy. Proteolytic enzymes such as matrix metalloproteinase (MMP) and closely related a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) have been assigned key roles in the highly regulated cyclic remodelling of the endometrial ECM. We have previously shown that ADAMTS-1 undergoes spatiotemporal changes in human endometrial stromal cells under the regulation of gonadal steroids. This suggests that other ADAMTS subtypes, known as aggrecanases, may contribute to the ECM remodelling events that occur in female physiological cycles and in preparation for pregnancy. To determine whether progesterone (P4), 17β-estradiol (E2), or dihydrotestosterone (DHT), alone or in combination, are capable of regulating ADAMTS-4, -5, -8 or -9 expression in human endometrial stromal cells in vitro. Real-time quantitative PCR and Western blot analysis were used to measure ADAMTSs mRNA and protein levels in primary cultures of human endometrial stromal cells (n = 12). P4, DHT but not E2 have regulatory effects on ADAMTS-8, -9 and -5 expression. Combined treatment with gonadal steroids did not show any synergistic or antagonistic effects. However, the synthetic steroid antagonists RU486 and hydroxyflutamide specifically inhibited the P4- or DHT-mediated regulatory effects on ADAMTS expression. These studies provide evidence that the regulation of aggrecanases by gonadal steroids in human endometrial stromal cells may play an important role during decidualization. PMID:23947778

Dimensional analysis of the endometrial cavity: how many dimensions should the ideal intrauterine device or system have?

PubMed

Goldstuck, Norman D

2018-01-01

The geometrical shape of the human uterus most closely approximates that of a prolate ellipsoid. The endometrial cavity itself is more likely to also have the shape of a prolate ellipsoid especially when the extension of the cervix is omitted. Using this information and known endometrial cavity volumes and lateral and vertical dimensions, it is possible to calculate the anteroposterior (AP) dimensions and get a complete evaluation of all possible dimensions of the endometrial cavity. These are singular observations and not part of any other study. The AP dimensions of the endometrial cavity of the uterus were calculated using the formula for the volume of the prolate ellipsoid to complete a three-dimensional picture of the endometrial cavity. Calculations confirm ultrasound imaging which shows large variations in cavity size and shape. Known cavity volumes and length and breadth measurements indicate that the AP diameter may vary from 6.29 to 38.2 mm. These measurements confirm the difficulty of getting a fixed-frame intrauterine device (IUD) to accommodate to a space of highly variable dimensions. This is especially true of three-dimension IUDs. A one-dimensional frameless IUD is most likely to be able to conform to this highly variable space and shape. The endometrial cavity may assume many varied prolate ellipsoid configurations where one or more measurements may be too small to accommodate standard IUDs. A one-dimensional device is most likely to be able to be accommodated by most uterine cavities as compared to two- and three-dimensional devices.

Mucinous expression in benign and neoplastic glandular lesions of the uterine cervix.

PubMed

Baker, Allyson C; Eltoum, Isam; Curry, Rebecca O; Stockard, Cecil R; Manne, Upender; Grizzle, William E; Chhieng, David

2006-10-01

Mucins are glycoproteins produced by both normal and neoplastic glandular epithelial cells including endocervix. To determine the expression of mucins in uterine cervical glandular lesions and whether mucin expression correlates with the nature and origin of the glandular lesions. Antibodies to MUC1, MUC2, MUC4, and MUC5AC were applied on 52 cases including 14 endocervical adenocarcinomas (including 4 adenosquamous carcinomas), 9 endometrial carcinomas (8 endometrioid adenocarcinomas and 1 adenosquamous carcinoma), 8 adenocarcinoma in situ (AIS), 2 glandular dysplasias, 6 tubal metaplasias, 10 microglandular hyperplasias, and 3 normal endocervix. The presence of any staining was considered positive. All benign endocervical epithelia, including tubal metaplasia and microglandular hyperplasia, expressed MUC1, MUC4, and MUC5AC but not MUC2. Almost all endocervical AIS and carcinomas and all endometrial adenocarcinomas expressed MUC1; the exceptions were 2 cases of endocervical adenocarcinoma and 1 case of adenosquamous carcinoma of the endocervix. MUC2 staining was noted in 25%, 40%, and 22% of AIS, endocervical adenocarcinomas, and endometrial adenocarcinomas, respectively. About 38% of AIS, 75% of endocervical adenocarcinomas, and 44% of endometrial adenocarcinomas expressed MUC4. Half of AIS, most of endocervical adenocarcinomas, and 22% of endometrial adenocarcinomas expressed MUC5AC. The difference in MUC4 and MUC5AC expression between benign endocervical lesions and AIS and the difference in MUC5AC expression between endocervical and endometrial neoplasms were statistically significant. Mucin expressions differed among benign endocervical lesions and AIS and among endocervical and endometrial malignancies. These results suggest that mucin staining may potentially be helpful in differentiating various uterine cervical glandular lesions.

The mucin expression profile of endometrial carcinoma and correlation with clinical-pathologic parameters.

PubMed

Morrison, Carl; Merati, Kambiz; Marsh, William L; De Lott, Lindsey; Cohn, David E; Young, Gregory; Frankel, Wendy L

2007-12-01

Mucin expression patterns have been studied in tumors from various sites. Previous studies have shown an association of MUC1 with poor prognosis and MUC2 and MUC5AC with a mucinous phenotype. The pattern of mucin expression in endometrial carcinomas has not been documented in a large series. We determined the mucin expression profile in endometrial carcinomas and evaluated the relationship between mucin expression and clinical-pathologic parameters. A tissue microarray of 310 cases of endometrial carcinoma with known clinical outcome was constructed from formalin-fixed, paraffin-embedded donor blocks using two 0.6 mm cores from each tumor. Sections were stained with monoclonal antibodies against MUC1, MUC2, MUC4, MUC5AC, and MUC6. Staining was considered positive if greater than or equal to 5% of cells stained positively in either core. Mucin expression was correlated with tumor type, histologic grade, International Federation Gynecology and Obstetrics stage, lymph node involvement, depth of myometrial invasion, patient age, ethnicity, and clinical outcome. MUC1 was expressed in 267/310 (86.1%) of endometrial carcinomas, MUC2 in 2/310 (0.6%), MUC4 in 73/310 (23.5%), MUC5AC in 1/310 (0.3%), and MUC6 in 4/310 (1.2%). Endometrioid endometrial carcinoma showed a higher rate of MUC1 expression than nonendometrioid endometrial carcinoma (227/258, 88.0% vs. 39/52, 75.0%, P=0.01). No significant differences in any of the mucins were noted among the other end points evaluated. Mucin expression did not correlate with tumor grade, stage, or patient outcome.

The Association of Plasminogen Activator Inhibitor Type 1 (PAI-1) Level and PAI-1 4G/5G Gene Polymorphism with the Formation and the Grade of Endometrial Cancer.

PubMed

Yıldırım, Malik Ejder; Karakuş, Savas; Kurtulgan, Hande Küçük; Kılıçgün, Hasan; Erşan, Serpil; Bakır, Sevtap

2017-08-01

Plasminogen activator inhibitor type 1 (PAI-1) is a serine protease inhibitor (Serpine 1), and it inhibits both tissue plasminogen activator and urokinase plasminogen activator which are important in fibrinolysis. We aimed to find whether there is a possible association between PAI-1 level, PAI-1 4G/5G polymorphism, and endometrial cancer. PAI-1 levels in peripheral blood were determined in 82 patients with endometrial carcinoma and 76 female healthy controls using an enzyme-linked immunoassay (ELISA). Then, the genomic DNA was extracted and screened by reverse hybridization procedure (Strip assay) to detect PAI 1 4G/5G polymorphism. The levels of PAI-1 in the patients were higher statistically in comparison to controls (P < 0.001). The distribution of PAI-1 4G/5G polymorphism was quite different between patients and controls (P = 0.008), and 4G allelic frequency was significantly higher in the patients of endometrial cancer than in controls (P = 0.026). We found significant difference between Grade 1 and Grade 2+3 patients in terms of the PAI-1 levels (P = 0.047). There was no association between PAI-1 4G/5G polymorphism and the grades of endometrial cancer (P = 0.993). Our data suggest that the level of PAI-1 and PAI-1 4G/5G gene polymorphism are effective in the formation of endometrial cancer. PAI-1 levels are also associated with the grades of endometrial cancer.

GPER and ERα expression in abnormal endometrial proliferations.

PubMed

Tica, Andrei Adrian; Tica, Oana Sorina; Georgescu, Claudia Valentina; Pirici, Daniel; Bogdan, Maria; Ciurea, Tudorel; Mogoantă, Stelian ŞtefăniŢă; Georgescu, Corneliu Cristian; Comănescu, Alexandru Cristian; Bălşeanu, Tudor Adrian; Ciurea, Raluca Niculina; Osiac, Eugen; Buga, Ana Maria; Ciurea, Marius Eugen

2016-01-01

G-protein coupled estrogen receptor 1 (GPER), a particular extranuclear estrogen receptor (ER), seems not to be significantly involved in normal female phenotype development but especially associated with severe genital malignancies. This study investigated the GPER expression in different types of normal and abnormal proliferative endometrium, and the correlation with the presence of ERα. GPER was much highly expressed in cytoplasm (than onto cell membrane), contrary to ERα, which was almost exclusively located in the nucleus. Both ERs' densities were higher in columnar epithelial then in stromal cells, according with higher estrogen-sensitivity of epithelial cells. GPER and ERα density decreased as follows: complex endometrial hyperplasia (CEH) > simple endometrial hyperplasia (SHE) > normal proliferative endometrium (NPE) > atypical endometrial hyperplasia (AEH), ERα' density being constantly higher. In endometrial adenocarcinomas, both ERs were significant lower expressed, and widely varied, but GPER÷ERα ratio was significantly increased in high-grade lesions. The nuclear ERα is responsible for the genomic (the most important) mechanism of action of estrogens, involved in cell growth and multiplication. In normal and benign proliferations, ERα expression is increased as an evidence of its effects on cells with conserved architecture, in atypical and especially in malignant cells ERα's (and GPER's) density being much lower. Cytoplasmic GPER probably interfere with different tyrosine÷protein kinases signaling pathways, also involved in cell growth and proliferation. In benign endometrial lesions, GPER's presence is, at least partially, the result of an inductor effect of ERα on GPER gene transcription. In high-grade lesions, GPER÷ERα ratio was increased, demonstrating that GPER is involved per se in malignant endometrial proliferations.

L1CAM expression in endometrial carcinomas: an ENITEC collaboration study

PubMed Central

van der Putten, Louis JM; Visser, Nicole CM; van de Vijver, Koen; Santacana, Maria; Bronsert, Peter; Bulten, Johan; Hirschfeld, Marc; Colas, Eva; Gil-Moreno, Antonio; Garcia, Angel; Mancebo, Gemma; Alameda, Fransesc; Trovik, Jone; Kopperud, Reidun K; Huvila, Jutta; Schrauwen, Stefanie; Koskas, Martin; Walker, Francine; Weinberger, Vit; Minar, Lubos; Jandakova, Eva; Snijders, Marc PLM; van den Berg-van Erp, Saskia; Matias-Guiu, Xavier; Salvesen, Helga B; Amant, Frederic; Massuger, Leon FAG; Pijnenborg, Johanna MA

2016-01-01

Background: Identification of aggressive endometrioid endometrial carcinomas (EECs) and non-endometrioid carcinomas (NEECs) is essential to improve outcome. L1 cell adhesion molecule (L1CAM) expression is a strong prognostic marker in stage I EECs, but less is known about L1CAM expression in advanced-stage EECs and NEECs. This study analyses L1CAM expression in a clinically representative cohort of endometrial carcinomas. Methods: The expression of L1CAM was immunohistochemically determined in 1199 endometrial carcinomas, treated at one of the European Network for Individualized Treatment of Endometrial Cancer (ENITEC) centres. Staining was considered positive when >10% of the tumour cells expressed L1CAM. The association between L1CAM expression and several clincopathological characteristics and disease outcome was calculated. Results: In all, L1CAM was expressed in 10% of the 935 stage I EECs, 18% of the 160 advanced stage EECs, and 75% of the 104 NEECs. The expression of L1CAM was associated with advanced stage, nodal involvement, high tumour grade, non-endometrioid histology, lymphovascular space invasion, and distant recurrences in all cases, and with reduced survival in the EECs, but not in the NEECs. Conclusions: The expression of L1CAM is a strong predictor of poor outcome in EECs, but not NEECs. It is strongly associated with non-endometrioid histology and distant spread, and could improve the postoperative selection of high-risk endometrial carcinomas. The value of L1CAM expression in the preoperative selection of high-risk endometrial carcinomas should be studied. PMID:27505134

Structural changes in endometrial basal glands during menstruation.

PubMed

Garry, R; Hart, R; Karthigasu, K A; Burke, C

2010-09-01

To prospectively observe the changes occurring in endometrial glandular morphology during menstrual shedding and regeneration. Prospective observational study. The academic gynaecological endoscopy unit of a university teaching hospital. Population Thirteen patients investigated for a variety of benign, non-infective gynaecological disorders during the active bleeding phase of the menstrual cycle. The morphological appearances of concurrent histological and scanning electron microscopic images of endometrium taken at different stages of the active bleeding phase of menstruation were studied and correlated with the simultaneous immunohistochemical expression of the Ki-67 proliferation marker and the CD68 marker of macrophage activity. Change in morphology of endometrial glands at various stages of menstruation. Endometrial glands within the basalis show evidence of apoptosis and associated macrophage activity immediately before and during menstruation. There is subsequent destruction and removal of old secretory glandular epithelial elements, and rapid replacement with new narrow glands lined with small epithelial cells. There is no evidence of mitotic cell division or expression of Ki-67 in the glandular cells during this replacement process, but there is evidence of marked macrophage activity prior to glandular cell loss. Early endometrial epithelial repair after menstruation is not a consequence of mitotic cell division. It occurs without evidence of Ki-67 expression. There is structural evidence of programmed cell death and intense macrophage activity associated with glandular remodelling. Dead epithelial cells are shed from the glands and accumulate within the endometrial cavity to be replaced by new small epithelial cells that appear to arise by differentiation of the surrounding stromal cells. We propose that these stromal cells are endometrial progenitor/stem cells.

Endometrial cancer with congenital uterine anomalies: 3 case reports and a literature review.

PubMed

Gao, Jinping; Zhang, Jintian; Tian, Wenyan; Teng, Fei; Zhang, Huiying; Zhang, Xuhong; Wang, Yingmei; Xue, Fengxia

2017-03-04

Uterine malformation is a rare deformity in woman, and only a few cases concerning endometrial cancer arising in patients with congenital uterine anomalies have been reported. Herein, we present 3 cases of endometrial cancer with different congenital uterine anomalies, and review studies involving congenital uterine anomalies associated with endometrial cancer in the past 25 years, to identify similarities and differences in clinicopathologic characteristics and prognosis between endometrial cancer associated with uterine anomalies, and normal uterus. Case 1 was a 75-year-old gravida 1, para 0, woman with carcinosarcoma (mixed well-differentiated endometrial adenocarcinoma and undifferentiated sarcoma) of the right cavity (grade III, and at least stage II ) of a uterus didelphys. The tumor recurred within 7 months after surgery, salvage radiotherapy was unsuccessful; the patient died 8 months after the surgery. Case 2 was a 63-year-old gravida 5, para 3, woman with a bicornuate uterus and uterus papillary serous carcinoma of the right horn (grade III, stage IIIC). She did not respond to the chemotherapy post surgery and died within 4 months. Case 3 was a 60-year-old gravida 0, para 0, woman with a complete septate uterus and an oblique vaginal septum of the upper region of the vagina with endometrioid adenocarchcinoma of the left cavity (grade II, stage IA). No adjuvant therapy was administered and the patient had recovered 2 y after the surgery. Clinicians should be aware of the coexistence of uterine malignancies and uterine anomalies in patients presenting with persistent abnormal uterine bleeding, but with negative endometrial biopsy or failed in the operation of endometrial biopsy. In such cases, magnetic resonance imaging has an important role in the diagnosis of both malformation and malignancy, and an exploratory laparotomy should be performed to avoid delaying the diagnosis and treatment of cancers.

Endometrial scratching in women with implantation failure after a first IVF/ICSI cycle; does it lead to a higher live birth rate? The SCRaTCH study: a randomized controlled trial (NTR 5342).

PubMed

van Hoogenhuijze, N E; Torrance, H L; Mol, F; Laven, J S E; Scheenjes, E; Traas, M A F; Janssen, C; Cohlen, B; Teklenburg, G; de Bruin, J P; van Oppenraaij, R; Maas, J W M; Moll, E; Fleischer, K; van Hooff, M H; de Koning, C; Cantineau, A; Lambalk, C B; Verberg, M; Nijs, M; Manger, A P; van Rumste, M; van der Voet, L F; Preys-Bosman, A; Visser, J; Brinkhuis, E; den Hartog, J E; Sluijmer, A; Jansen, F W; Hermes, W; Bandell, M L; Pelinck, M J; van Disseldorp, J; van Wely, M; Smeenk, J; Pieterse, Q D; Boxmeer, J C; Groenewoud, E R; Eijkemans, M J C; Kasius, J C; Broekmans, F J M

2017-07-21

Success rates of assisted reproductive techniques (ART) are approximately 30%, with the most important limiting factor being embryo implantation. Mechanical endometrial injury, also called 'scratching', has been proposed to positively affect the chance of implantation after embryo transfer, but the currently available evidence is not yet conclusive. The primary aim of this study is to determine the effect of endometrial scratching prior to a second fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle on live birth rates in women with a failed first IVF/ICSI cycle. Multicenter randomized controlled trial in Dutch academic and non-academic hospitals. A total of 900 women will be included of whom half will undergo an endometrial scratch in the luteal phase of the cycle prior to controlled ovarian hyperstimulation using an endometrial biopsy catheter. The primary endpoint is the live birth rate after the 2 nd fresh IVF/ICSI cycle. Secondary endpoints are costs, cumulative live birth rate (after the full 2 nd IVF/ICSI cycle and over 12 months of follow-up); clinical and ongoing pregnancy rate; multiple pregnancy rate; miscarriage rate and endometrial tissue parameters associated with implantation failure. Multiple studies have been performed to investigate the effect of endometrial scratching on live birth rates in women undergoing IVF/ICSI cycles. Due to heterogeneity in both the method and population being scratched, it remains unclear which group of women will benefit from the procedure. The SCRaTCH trial proposed here aims to investigate the effect of endometrial scratching prior to controlled ovarian hyperstimulation in a large group of women undergoing a second IVF/ICSI cycle. NTR 5342 , registered July 31 st , 2015. Version 4.10, January 4th, 2017.

Endometrial cancer with congenital uterine anomalies: 3 case reports and a literature review

PubMed Central

Gao, Jinping; Zhang, Jintian; Tian, Wenyan; Teng, Fei; Zhang, Huiying; Zhang, Xuhong; Wang, Yingmei; Xue, Fengxia

2017-01-01

ABSTRACT Background: Uterine malformation is a rare deformity in woman, and only a few cases concerning endometrial cancer arising in patients with congenital uterine anomalies have been reported. Herein, we present 3 cases of endometrial cancer with different congenital uterine anomalies, and review studies involving congenital uterine anomalies associated with endometrial cancer in the past 25 years, to identify similarities and differences in clinicopathologic characteristics and prognosis between endometrial cancer associated with uterine anomalies, and normal uterus. Cases: Case 1 was a 75-year-old gravida 1, para 0, woman with carcinosarcoma (mixed well-differentiated endometrial adenocarcinoma and undifferentiated sarcoma) of the right cavity (grade III, and at least stage II ) of a uterus didelphys. The tumor recurred within 7 months after surgery, salvage radiotherapy was unsuccessful; the patient died 8 months after the surgery. Case 2 was a 63-year-old gravida 5, para 3, woman with a bicornuate uterus and uterus papillary serous carcinoma of the right horn (grade III, stage IIIC). She did not respond to the chemotherapy post surgery and died within 4 months. Case 3 was a 60-year-old gravida 0, para 0, woman with a complete septate uterus and an oblique vaginal septum of the upper region of the vagina with endometrioid adenocarchcinoma of the left cavity (grade II, stage IA). No adjuvant therapy was administered and the patient had recovered 2 y after the surgery. Conclusion: Clinicians should be aware of the coexistence of uterine malignancies and uterine anomalies in patients presenting with persistent abnormal uterine bleeding, but with negative endometrial biopsy or failed in the operation of endometrial biopsy. In such cases, magnetic resonance imaging has an important role in the diagnosis of both malformation and malignancy, and an exploratory laparotomy should be performed to avoid delaying the diagnosis and treatment of cancers. PMID:28118070

Association between dietary fiber and endometrial cancer: a dose-response meta-analysis123

PubMed Central

Bandera, Elisa V; Kushi, Lawrence H; Moore, Dirk F; Gifkins, Dina M; McCullough, Marjorie L

2008-01-01

Background Endometrial cancer is the most common female gynecologic cancer in the United States. Excessive and prolonged exposure of the endometrium to estrogens unopposed by progesterone and a high body mass are well-established risk factors for endometrial cancer. Although dietary fiber has been shown to beneficially reduce estrogen concentrations and prevent obesity, its role in endometrial cancer has received relatively little attention. Objective The objective was to summarize and quantify the current evidence of a role of dietary fiber consumption in endometrial cancer risk and to identify research gaps in this field. Design We conducted a systematic literature review of articles published through February 2007 to summarize the current evidence of a relation between dietary fiber consumption and endometrial cancer risk and to quantify the magnitude of the association by conducting a dose-response meta-analysis. Results Ten articles representing 1 case-cohort study and 9 case-control studies that evaluated several aspects of fiber consumption and endometrial cancer risk were identified through searches in various databases. On the basis of 7 case-control studies, the random-effects summary risk estimate was 0.82 (95% CI: 0.75, 0.90) per 5 g/1000 kcal dietary fiber, with no evidence of heterogeneity (I2: 0%, P for heterogeneity: 0.55). The random-effects summary estimate was 0.71 (95% CI: 0.59, 0.85) for the comparison of the highest with the lowest dietary fiber intake in 8 case-control studies, with little evidence of heterogeneity (I2: 20.8%, P for heterogeneity: 0.26). In contrast, the only prospective study that evaluated this association did not find an association. Conclusions Although the current evidence, based on data from case-control studies, supports an inverse association between dietary fiber and endometrial cancer, additional population-based studies, particularly cohort studies, are needed before definitive conclusions can be drawn. PMID:18065593

[Surgical treatment of precancer and cancer of endometrium].

PubMed

Ivanov, S; Khadzhiolov, N; Batashki, I

2007-01-01

Our aim was to evaluate occult presence of endometrial cancer in patients with atypical glandular hiperplasia and to compare the histological prognostic factors according to the status of the lymph nodes and the grading of the occult tumour. 306 patients were evaluated retrospectvely for the period of 1990-2007. They were operated one month after the hostological diagnostic atypical glandular hiperplasia obtained by D&C. All patients were with vaginal bleeding. The patients who had concomitant presence of endometrial hyperplasia and endometrial cancer were excluded from the study. One hundred patients (group A) with atypical glandular hyperplasia were compared with 206 patients (group B) without atypical glandular hyperplasia obtained by D&C. Mann and Witney test and chi-square test were used for statistical evaluation.. There was no difference between the age and the menopausal status in the two groups, only there was higher parity in group B. In group A patients with atypical glandular hyperlasia we found in 50% endometrial cancer intraoperatively, in 40% endometrial hyperplasia and in 10% normal endometrium. In the second group B were included the patients without atypical hyperplasia from D&C. In group B were found in 6% endometrial cancer in 44% endometrial hyperplasia and in 50% normal endometrium. In 30 patients was performed complete surgical staging. Six patients were with metastatic lymph nodes. All of them were with grading 2 (4 patients) and grading 3 (2 patients), and also with infiltration in the lymph-vascular spaces. Four patients were with nonendometrioid tumours (type 2 endometrial cancer). The careful preoperative and intraoperative evaluation of the endometrium is very important in patients with atypical glandular hyperplasia. It is reasonable to use frozen section in the time of hysterectomy for patients with atypical glandular hyperplasia. If tumour with grading 2/3 nonendometrioid cancer with lymph-vascular space invasion, is found-complete surgical staging is needed.

Reversible inhibition of lysine specific demethylase 1 is a novel anti-tumor strategy for poorly differentiated endometrial carcinoma.

PubMed

Theisen, Emily R; Gajiwala, Snehal; Bearss, Jared; Sorna, Venkataswamy; Sharma, Sunil; Janat-Amsbury, Margit

2014-10-09

Endometrial cancer is the most common gynecologic malignancy. Type II endometrial carcinoma is often poorly differentiated and patients diagnosed with Type II disease (~11%) are disproportionately represented in annual endometrial cancer deaths (48%). Recent genomic studies highlight mutations in chromatin regulators as drivers in Type II endometrial carcinoma tumorigenesis, suggesting the use of epigenetic targeted therapies could provide clinical benefit to these patients. We investigated the anti-tumor efficacy of the LSD1 inhibitor HCI2509 in two poorly differentiated Type II endometrial cancer cell lines AN3CA and KLE. The effects of HCI2509 on viability, proliferation, anchorage-independent growth, global histone methylation, LSD1 target gene induction, cell cycle, caspase activation and TUNEL were assayed. KLE cells were used in an orthotopic xenograft model to assess the anti-tumor activity of HCI2509. Both AN3CA and KLE cells were sensitive to HCI2509 treatment with IC50s near 500 nM for cell viability. Inhibition of LSD1 with HCI2509 caused decreased proliferation and anchorage independent growth in soft agar, elevated global histone methylation, and perturbed the cell cycle in both cell lines. These effects were largely dose-dependent. HCI2509 treatment also caused apoptotic cell death. Orthotopic implantation of KLE cells resulted in slow-growing and diffuse tumors throughout the abdomen. Tumor burden was distributed log-normally. Treatment with HCI2509 resulted 5/9 tumor regressions such that treatment and regressions were significantly associated (p=0.034). Our findings demonstrate the anti-cancer properties of the LSD1 inhibitor HCI2509 on poorly differentiated endometrial carcinoma cell lines, AN3CA and KLE. HCI2509 showed single-agent efficacy in orthotopic xenograft studies. Continued studies are needed to preclinically validate LSD1 inhibition as a therapeutic strategy for endometrial carcinoma.

Lynch syndrome-associated endometrial carcinoma with MLH1 germline mutation and MLH1 promoter hypermethylation: a case report and literature review.

PubMed

Yokoyama, Takanori; Takehara, Kazuhiro; Sugimoto, Nao; Kaneko, Keika; Fujimoto, Etsuko; Okazawa-Sakai, Mika; Okame, Shinichi; Shiroyama, Yuko; Yokoyama, Takashi; Teramoto, Norihiro; Ohsumi, Shozo; Saito, Shinya; Imai, Kazuho; Sugano, Kokichi

2018-05-21

Lynch syndrome is an autosomal dominant inherited disease caused by germline mutations in mismatch repair genes. Analysis for microsatellite instability (MSI) and immunohistochemistry (IHC) of protein expressions of disease-associated genes is used to screen for Lynch syndrome in endometrial cancer patients. When losses of both MLH1 and PMS2 proteins are observed by IHC, MLH1 promoter methylation analysis is conducted to distinguish Lynch syndrome-associated endometrial cancer from sporadic cancer. Here we report a woman who developed endometrial cancer at the age of 49 years. She had a family history of colorectal cancer (first-degree relative aged 52 years) and stomach cancer (second-degree relative with the age of onset unknown). No other family history was present, and she failed to meet the Amsterdam II criteria for the diagnosis of Lynch syndrome. Losses of MLH1 and PMS2, but not MSH2 and MSH6, proteins were observed by IHC in endometrial cancer tissues. Because MLH1 promoter hypermethylation was detected in endometrial cancer tissue samples, the epigenetic silencing of MLH1 was suspected as the cause of the protein loss. However, because of the early onset of endometrial cancer and the positive family history, a diagnosis of Lynch syndrome was also suspected. Therefore, we provided her with genetic counseling. After obtaining her consent, MLH1 promoter methylation testing and genetic testing of peripheral blood were performed. MLH1 promoter methylation was not observed in peripheral blood. However, genetic testing revealed a large deletion of exon 5 in MLH1; thus, we diagnosed the presence of Lynch syndrome. Both MLH1 germline mutation and MLH1 promoter hypermethylation may be observed in endometrial cancer. Therefore, even if MLH1 promoter hypermethylation is detected, a diagnosis of Lynch syndrome cannot be excluded.

Clinical outcomes in endometrial cancer care when the standard of care shifts from open surgery to robotics.

PubMed

Mok, Zhun Wei; Yong, Eu Leong; Low, Jeffrey Jen Hui; Ng, Joseph Soon Yau

2012-06-01

In Singapore, the standard of care for endometrial cancer staging remains laparotomy. Since the introduction of gynecologic robotic surgery, there have been more data comparing robotic surgery to laparoscopy in the management of endometrial cancer. This study reviewed clinical outcomes in endometrial cancer in a program that moved from laparotomy to robotic surgery. A retrospective review was performed on 124 consecutive endometrial cancer patients. Preoperative data and postoperative outcomes of 34 patients undergoing robotic surgical staging were compared with 90 patients who underwent open endometrial cancer staging during the same period and in the year before the introduction of robotics. There were no significant differences in the mean age, body mass index, rates of diabetes, hypertension, previous surgery, parity, medical conditions, size of specimens, histologic type, or stage of cancer between the robotic and the open surgery groups. The first 20 robotic-assisted cases had a mean (SD) operative time of 196 (60) minutes, and the next 14 cases had a mean time of 124 (64) minutes comparable to that for open surgery. The mean number of lymph nodes retrieved during robot-assisted staging was smaller than open laparotomy in the first 20 cases but not significantly different for the subsequent 14 cases. Robot-assisted surgery was associated with lower intraoperative blood loss (110 [24] vs 250 [83] mL, P < 0.05), a lower rate of postoperative complications (8.8% vs 26.8%, P = 0.032), a lower wound complication rate (0% vs 9.9%, P = 0.044), a decreased requirement for postoperative parenteral analgesia (5.9% vs 51.1, P < 0.001), and shorter length of hospitalization (2.0 [1.1] vs 6.0 [4.5] days, P < 0.001) compared to patients in the open laparotomy group. Our series shows that outcomes traditionally associated with laparoscopic endometrial cancer staging are achievable by laparoscopy-naive gynecologic cancer surgeons moving from laparotomy to robot-assisted endometrial cancer staging after a relatively small number of cases.

Reduced connexin 43 in eutopic endometrium and cultured endometrial stromal cells from subjects with endometriosis

PubMed Central

Yu, Jie; Boicea, Anisoara; Barrett, Kara L.; James, Christopher O.; Bagchi, Indrani C.; Bagchi, Milan K.; Nezhat, Ceana; Sidell, Neil; Taylor, Robert N.

2014-01-01

Accumulating evidence indicates that reduced fecundity associated with endometriosis reflects a failure of embryonic receptivity. Microdomains composed of endometrial gap junctions, which facilitate cell–cell communication, may be implicated. Pharmacological or genetic inhibition of connexin (Cx) 43 block human endometrial cell differentiation in vitro and conditional uterine deletion of Cx43 alleles cause implantation failure in mice. The aim of this study was to determine whether women with endometriosis have reduced eutopic endometrial Cx43. Cx26 acted as a control. Endometrial biopsies were collected from age, race and cycle phase-matched women without (15 controls) or with histologically confirmed endometriosis (15 cases). Immunohistochemistry confirmed a predominant localization of Cx43 in the endometrial stroma, whereas Cx26 was confined to the epithelium. Cx43 immunostaining was reduced in eutopic biopsies of endometriosis subjects and western blotting of tissue lysates confirmed lower Cx43 levels in endometriosis cases, with Cx43/β-actin ratios =3.4 ± 1.5 in control and =1.2 ± 0.3 in endometriosis biopsies (P < 0.01). When endometrial stromal cells (ESC) were isolated from endometriosis cases, Cx43 levels and scrape loading-dye transfer were reduced by ∼45% compared with ESC from controls. In vitro decidualization of ESC derived from endometriosis versus control subjects resulted in lesser epithelioid transformation and a significantly reduced up-regulation of Cx43 protein (1.2 ± 0.2- versus 1.7 ± 0.4-fold, P < 0.01). No changes in Cx26 were observed. While basal steady-state levels of Cx43 mRNA did not differ with respect to controls, ESC from endometriosis cases failed to manifest a response to hormone treatment in vitro. In summary, eutopic endometrial Cx43 concentrations in endometriosis cases were <50% those of controls in vivo and in vitro, functional gap junctions were reduced and hormone-induced Cx43 mRNA levels were blunted. PMID:24270393

Indoleamine 2,3-dioxygenase in endometrial cancer: a targetable mechanism of immune resistance in mismatch repair-deficient and intact endometrial carcinomas.

PubMed

Mills, Anne; Zadeh, Sara; Sloan, Emily; Chinn, Zachary; Modesitt, Susan C; Ring, Kari L

2018-03-20

Mismatch repair-deficient endometrial carcinomas are optimal candidates for immunotherapy given their high neoantigen loads, robust lymphoid infiltrates, and frequent PD-L1 expression. However, co-opting the PD-1/PD-L1 pathway is just one mechanism that tumors can utilize to evade host immunity. Another immune modulatory molecule that has been demonstrated in endometrial carcinoma is indoleamine 2,3-dioxygenase (IDO). We herein evaluate IDO expression in 60 endometrial carcinomas and assess results in relation to PD-L1 and mismatch repair status. IDO immunohistochemistry was performed on 60 endometrial carcinomas (20 Lynch syndrome (LS)-associated, 20 MLH1 promoter hypermethylated, and 20 mismatch repair-intact). Eight-five percent of endometrial carcinomas showed IDO tumor staining in >1% of cells. Twenty-five percent were positive in >25% of tumor cells and only 7% exceeded 50% staining. Mismatch repair-deficient cancers were more likely than mismatch repair-intact cancers to be >25% IDO-positive (35% vs. 5% p = 0.024). Differences were amplified when Lynch syndrome-associated cases were evaluated in isolation (50% Lynch syndrome-associated vs. 10% mismatch repair-intact and MLH1-hypermethylated, p = 0.001). Of the four cases showing >50% staining, three were Lynch syndrome-associated and one was MLH1-hypermethylated; no mismatch repair-intact cases had >50% staining. Forty-three percent of IDO-positive tumors were also positive for PD-L1, whereas only two cases showed tumoral PD-L1 in the absence of IDO. In summary, IDO expression is prevalent in endometrial carcinomas and diffuse staining is significantly more common in mismatch repair-deficient cancers, particularly Lynch syndrome-associated cases. Given that the majority of PD-L1 positive cancers also express IDO, synergistic combination therapy with anti-IDO and anti-PD1/PD-L1 may be relevant in this tumor type. Furthermore, anti-IDO therapy may be an option for a small subset of mismatch repair-intact cancers.

Galectin-7 is important for normal uterine repair following menstruation.

PubMed

Evans, Jemma; Yap, Joanne; Gamage, Thillini; Salamonsen, Lois; Dimitriadis, Evdokia; Menkhorst, Ellen

2014-08-01

Menstruation involves the shedding of the functional layer of the endometrium in the absence of pregnancy. At sites where tissue shedding is complete, re-epithelialization of the tissue is essential for repair and termination of bleeding. The complement of growth factors that mediate post-menstrual endometrial repair are yet to be completely elucidated. Galectins regulate many cell functions important for post-menstrual repair, such as cell adhesion and migration. Galectin-7 has a well characterized role in re-epithelialization and wound healing. We hypothesized that galectin-7 would be important in re-epithelialization during post-menstrual repair. We aimed to identify endometrial expression of galectin-7 in women undergoing normal endometrial repair and in women with amenorrhoea who do not experience endometrial breakdown and repair, and to determine whether galectin-7 enhances endometrial re-epithelialization in vitro. Galectin-7 immunolocalized to the endometrial luminal and glandular epithelium during the late secretory and menstrual phases, and to decidualized stroma in regions exhibiting tissue breakdown. Immunostaining intensity was significantly reduced in the endometrium of women with amenorrhoea compared with normally cycling woman. ELISA identified galectin-7 in menstrual fluid at significantly elevated levels compared with matched peripheral plasma. Exogenous galectin-7 (2.5 µg/ml) significantly enhanced endometrial epithelial wound repair in vitro; this was abrogated by inhibition of integrin binding. Galectin-7 elevated epithelial expression of extracellular matrix-related molecules likely involved in repair including β-catenin, contactin and TGF-β1. In conclusion, galectin-7 is produced by the premenstrual and menstrual endometrium, where it accumulates in menstrual fluid and likely acts as a paracrine factor to facilitate post-menstrual endometrial re-epithelialization. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Expression of GRIM-19 in adenomyosis and its possible role in pathogenesis.

PubMed

Wang, Jing; Deng, Xiaohui; Yang, Yang; Yang, Xingsheng; Kong, Beihua; Chao, Lan

2016-04-01

To study the expression of the gene associated with retinoid-interferon (IFN)-induced mortality 19 (GRIM-19) in the endometrial tissue of patients with adenomyosis and to describe the possible pathogenic mechanisms of this phenomenon. Experimental study using human samples and cell lines. University-affiliated hospital. Ectopic and eutopic endometrial tissues were obtained from 30 patients with adenomyosis, whereas normal endometrial specimens were obtained from 10 control patients without adenomyosis. Patients with rapid pathology report-confirmed adenomyosis were recruited, and eutopic and ectopic endometrial tissue samples were collected from patients who had undergone hysterectomies by either the transabdominal or laparoscopic method at Qilu Hospital. Normal endometrial tissue was collected from a group of control patients without adenomyosis. Immunohistochemistry (IHC) was performed to evaluate the expression of GRIM-19, phospho-signal transducer and activator of transcription 3 (Y705) (Y705) (pSTAT3(Y705)), and vascular endothelial growth factor (VEGF) in endometrial tissue samples. The protein levels of GRIM-19, pSTAT3(Y705), STAT3, and VEGF were detected by Western blot. Apoptosis in endometrial specimens was assayed by TUNEL. Immunohistochemistry with an antibody directed against CD34 was performed to detect new blood vessels in the endometrial tissue. GRIM-19 small interfering RNA and a recombinant plasmid carrying GRIM-19 were constructed to evaluate the effects of GRIM-19 on the downstream factors pSTAT3(Y705), STAT3, and VEGF in Ishikawa cells. The expression of GRIM-19 was down-regulated in the eutopic endometria of patients with adenomyosis compared with the endometria of patients in the control group, and it was further reduced in the endometrial glandular epithelial cells of adenomyotic lesions. Apoptosis was reduced in the eutopic endometrium compared with the control group, and it was significantly reduced in ectopic endometrial tissues. In addition, the ectopic and eutopic endometria of patients with adenomyosis displayed a much higher microvessel density. In the eutopic and ectopic endometria of patients with adenomyosis, the expression levels of pSTAT3(Y705) and VEGF were significantly higher than in the controls. Furthermore, down-regulation of GRIM-19 in Ishikawa cells significantly promoted the activation of both pSTAT3(Y705) and its dependent gene VEGF. Aberrant expression of GRIM-19 may be associated with adenomyosis through the regulation of apoptosis and angiogenesis. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Hox proteins activate the IGFBP-1 promoter and suppress the function of hPR in human endometrial cells.

PubMed

Gao, Jiaguo; Mazella, James; Tseng, Linda

2002-11-01

Previous studies have shown that progestin activates the transcription of IGFBP-1 (insulin-like growth factor binding protein-1). Four regions in the IGFBP-1 promotor have been identified to enhance the transcription. Two of the regions, located at -73 to -65 bp and -319 to -311 bp formed identical DNA-protein complexes with the nuclear extracts of endometrial stromal/decidual cells. To identify the binding protein(s) in endometrial cells that interact with these two regions, we have used the TGTCAATTA repeats (-319 to -11 bp of the IGFBP-1 promoter) to screen the human decidual cDNA library by yeast one-hybrid system. We found that Hox A10, HoxA11, HoxB2, HoxB4, and HoxD11 interacted with the TGTCAATTA repeats in yeast cells. Among these hox genes, the full-length coding region of HoxA10, HoxA11, and HoxB4 were used for functional analysis in three types of endometrial cells, undifferentiated endometrial stromal cells, decidual cells (differentiated stromal cells) and endometrial adenocarcinoma cell line (HEC1-B). All these endometrial cells produce IGFBP-1. Transient transfection assay showed that HoxA10 expression vector increased the promoter activity (the IGFBP-1 proximal promoter containing TGC/TCAATTA and two functional PRE sites) in endometrial stromal cells and in HEC-1B cells, but not in decidual cells. HoxB4 enhanced the promoter activity only in decidual cells, while HoxA11 had no apparent effect in all three types of cells. To evaluate whether Hox proteins would interact with progesterone receptor (hPR), cells were transfected with the promoter construct, Hox and hPR expression vectors. hPR alone activated the IGFBP-1 promoter activity, but expression of Hox gene suppressed the activation. Hox proteins also suppressed the hPR enhanced promoter activities of MMTV (containing consensus-PRE sites) and glycodelin (GdA, containing Sp1 site which mediates the hPR function). These data showed that Hox genes selectively activate the transcription of the IGFBP-1 and GdA genes in different types of endometrial cells. Hox genes, however, suppress the hPR enhanced activities. In addition, we found that HoxB4 expression was induced by estrogen and progestin. Other investigators have shown that HoxA10 and 11 were stimulated by progestin. These findings show that Hox proteins are molecular mediators of the steroid hormones during endometrial cell development.

Reduced homeobox protein MSX1 in human endometrial tissue is linked to infertility.

PubMed

Bolnick, Alan D; Bolnick, Jay M; Kilburn, Brian A; Stewart, Tamika; Oakes, Jonathan; Rodriguez-Kovacs, Javier; Kohan-Ghadr, Hamid-Reza; Dai, Jing; Diamond, Michael P; Hirota, Yasushi; Drewlo, Sascha; Dey, Sudhansu K; Armant, D Randall

2016-09-01

Is protein expression of the muscle segment homeobox gene family member MSX1 altered in the human secretory endometrium by cell type, developmental stage or fertility? MSX1 protein levels, normally elevated in the secretory phase endometrium, were significantly reduced in endometrial biopsies obtained from women of infertile couples. Molecular changes in the endometrium are important for fertility in both animals and humans. Msx1 is expressed in the preimplantation mouse uterus and regulates uterine receptivity for implantation. The MSX protein persists a short time, after its message has been down-regulated. Microarray analysis of the human endometrium reveals a similar pattern of MSX1 mRNA expression that peaks before the receptive period, with depressed expression at implantation. Targeted deletion of uterine Msx1 and Msx2 in mice prevents the loss of epithelial cell polarity during implantation and causes infertility. MSX1 mRNA and cell type-specific levels of MSX1 protein were quantified from two retrospective cohorts during the human endometrial cycle. MSX1 protein expression patterns were compared between fertile and infertile couples. Selected samples were dual-labeled by immunofluorescence microscopy to localize E-cadherin and β-catenin in epithelial cells. MSX1 mRNA was quantified by PCR in endometrium from hysterectomies (n = 14) determined by endometrial dating to be in the late-proliferative (cycle days 10-13), early-secretory (cycle days 14-19) or mid-secretory (cycle days 20-24) phase. MSX1 protein was localized using high-throughput, semi-quantitative immunohistochemistry with sectioned endometrial biopsy tissues from fertile (n = 89) and infertile (n = 89) couples. Image analysis measured stain intensity specifically within the luminal epithelium, glands and stroma during the early-, mid- and late- (cycle days 25-28) secretory phases. MSX1 transcript increased 5-fold (P < 0.05) between the late-proliferative and early secretory phase and was then down-regulated (P < 0.05) prior to receptivity for implantation. In fertile patients, MSX1 protein displayed strong nuclear localization in the luminal epithelium and glands, while it was weakly expressed in nuclei of the stroma. MSX1 protein levels accumulated throughout the secretory phase in all endometrial cellular compartments. MSX1 protein decreased (P < 0.05) in the glands between mid- and late-secretory phases. However, infertile patients demonstrated a broad reduction (P < 0.001) of MSX1 accumulation in all cell types throughout the secretory phase that was most pronounced (∼3-fold) in stroma and glands. Infertility was associated with persistent co-localization of E-cadherin and β-catenin in epithelial cell junctions in the mid- and late-secretory phases. Details of the infertility diagnoses and other patient demographic data were not available. Therefore, patients with uterine abnormalities (Mullerian) could not be distinguished from other sources of infertility. Antibody against human MSX2 is not available, limiting the study to MSX1. However, both RNAs in the human endometrium are similarly regulated. In mice, Msx1 and Msx2 are imperative for murine embryo implantation, with Msx2 compensating for genetic ablation of Msx1 through its up-regulation in a knockout model. This investigation establishes that the MSX1 homeobox protein accumulation is associated with the secretory phase in endometrium of fertile couples, and is widely disrupted in infertile patients. It is the first study to examine MSX1 protein localization in the human endometrium, and supported by genetic findings in mice, suggests that genes regulated by MSX1 are linked to the loss of epithelial cell polarity required for uterine receptivity during implantation. This research was supported by the NICHD National Cooperative Reproductive Medicine Network grant HD039005 (M.P.D.), NIH grants HD068524 (S.K.D.), HD071408 (D.R.A., M.P.D.), and HL128628 (S.D.), the Intramural Research Program of the NICHD, March of Dimes (S.K.D., S.D.) and JSPS KAKENHI grant 26112506 (Y.H.). There were no conflicts or competing interests. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Concurrent primaries of vaginal clear cell adenocarcinoma and endometrial adenocarcinoma in a 39-year old woman with in utero diethylstilbestrol exposure.

PubMed

Keller, C; Nanda, R; Shannon, R L; Amit, A; Kaplan, A L

2001-01-01

Diethylstilbestrol (DES) was used widely in the late 1940s in an attempt to prevent adverse pregnancy outcomes. In 1971 the US Food and Drug Administration proscribed its use for pregnancy support secondary to its association with clear cell adenocarcinoma of the vagina. Several studies in animal models demonstrated an association with endometrial cancer among offspring following in utero DES exposure. To date, there is only one case report of endometrial cancer in women exposed to DES in utero. We present the first case, to our knowledge, of a woman exposed to DES in utero who presented with double primaries of clear cell cancer of the vagina concomitant with endometrial cancer.

Molecular and functional aspects of menstruation in the macaque.

PubMed

Brenner, Robert M; Slayden, Ov D

2012-12-01

Much of our understanding of the molecular control of menstruation arises from laboratory models that experimentally recapitulate some, but not all, aspects of uterine bleeding observed in women. These models include: in vitro culture of endometrial explants or isolated endometrial cells, transplantation of human endometrial tissue into immunodeficient mice and the induction of endometrial breakdown in appropriately pretreated mice. Each of these models has contributed to our understanding of molecular and cellular mechanisms of menstruation, but nonhuman primates, especially macaques, are the animal model of choice for evaluating therapies for menstrual disorders. In this chapter we review some basic aspects of menstruation, with special emphasis on the macaque model and its relevance to the clinical issues of irregular and heavy menstrual bleeding (HMB).

21 CFR 884.1060 - Endometrial aspirator.

Code of Federal Regulations, 2011 CFR

2011-04-01

... and pipette, or catheter. This device is used to study endometrial cytology (cells). (b... endometrium, and (ii) Contraindications: Pregnancy, history of uterine perforation, or a recent cesarean...

21 CFR 884.1060 - Endometrial aspirator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... and pipette, or catheter. This device is used to study endometrial cytology (cells). (b... endometrium, and (ii) Contraindications: Pregnancy, history of uterine perforation, or a recent cesarean...

Are endometrial nerve fibres unique to endometriosis? A prospective case-control study of endometrial biopsy as a diagnostic test for endometriosis in women with pelvic pain.

PubMed

Ellett, Lenore; Readman, Emma; Newman, Marsali; McIlwaine, Kate; Villegas, Rocio; Jagasia, Nisha; Maher, Peter

2015-12-01

Can the presence of endometrial nerve fibres be used as a diagnostic test for endometriosis in women with pelvic pain? Endometrial fine nerve fibres were seen in the endometrium of women both with and without endometriosis, making their detection a poor diagnostic tool for endometriosis. Laparoscopy and biopsy are currently the gold standard for making a diagnosis of endometriosis. It has been reported that small density nerve fibres in the functional layer of the endometrium are unique to women with endometriosis and hence nerve fibre detection could function as a less invasive diagnostic test of endometriosis. However, it may be that other painful conditions of the pelvis are also associated with these nerve fibres. We therefore focused this prospective study on women with pelvic pain to examine the efficacy of endometrial nerve fibre detection as a diagnostic test for endometriosis. This prospective case-control study conducted between July 2009 and July 2013 included 44 women with pelvic pain undergoing laparoscopic examination for the diagnosis of endometriosis. Immunohistochemical nerve fibre detection in endometrial curettings and biopsies using anti-protein gene product 9.5 was compared with surgical diagnosis. Paired endometrial biopsies and curettings were taken from patients with (n = 22, study group) and without (n = 22, control group) endometriosis. Tissue was analysed by immunohistochemistry and nerve fibres were counted whenever they were present in the functional layer of the endometrium. Fine nerve fibres were present in the eutopic endometrium of patients both with and without endometriosis. The presence of nerve fibres in curettings was not effective for either diagnosing or excluding endometriosis; sensitivity and specificity were 31.8 and 45.5% respectively, positive predictive value was 36.8% and negative predictive value was 40.0%. Few endometrial biopsy specimens were found to have nerve fibres present; sensitivity and specificity for endometrial biopsy were 13.6 and 68.2% respectively, positive predictive value was 30.0% and negative predictive value was 44.1%. This was a relatively small sample size and studies like this are subject to the heterogeneous nature of the patient population and tissue samples, despite our best efforts to regulate these parameters. Our results demonstrate that fine nerve fibres are present in women with and without endometriosis. Future work should focus on the function of endometrial nerves and whether these nerves are involved with the subfertility or pain that endometriosis sufferers experience. Our study does not support the detection of endometrial nerve fibres as a non-invasive diagnostic test of endometriosis in women with pelvic pain. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

DNA profiling analysis of endometrial and ovarian cell lines reveals misidentification, redundancy and contamination.

PubMed

Korch, Christopher; Spillman, Monique A; Jackson, Twila A; Jacobsen, Britta M; Murphy, Susan K; Lessey, Bruce A; Jordan, V Craig; Bradford, Andrew P

2012-10-01

Cell lines derived from human ovarian and endometrial cancers, and their immortalized non-malignant counterparts, are critical tools to investigate and characterize molecular mechanisms underlying gynecologic tumorigenesis, and facilitate development of novel therapeutics. To determine the extent of misidentification, contamination and redundancy, with evident consequences for the validity of research based upon these models, we undertook a systematic analysis and cataloging of endometrial and ovarian cell lines. Profiling of cell lines by analysis of DNA microsatellite short tandem repeats (STR), p53 nucleotide polymorphisms and microsatellite instability was performed. Fifty-one ovarian cancer lines were profiled with ten found to be redundant and five (A2008, OV2008, C13, SK-OV-4 and SK-OV-6) identified as cervical cancer cells. Ten endometrial cell lines were analyzed, with RL-92, HEC-1A, HEC-1B, HEC-50, KLE, and AN3CA all exhibiting unique, uncontaminated STR profiles. Multiple variants of Ishikawa and ECC-1 endometrial cancer cell lines were genotyped and analyzed by sequencing of mutations in the p53 gene. The profile of ECC-1 cells did not match the EnCa-101 tumor, from which it was reportedly derived, and all ECC-1 isolates were genotyped as Ishikawa cells, MCF-7 breast cancer cells, or a combination thereof. Two normal, immortalized endometrial epithelial cell lines, HES cells and the hTERT-EEC line, were identified as HeLa cervical carcinoma and MCF-7 breast cancer cells, respectively. Results demonstrate significant misidentification, duplication, and loss of integrity of endometrial and ovarian cancer cell lines. Authentication by STR DNA profiling is a simple and economical method to verify and validate studies undertaken with these models. Copyright © 2012 Elsevier Inc. All rights reserved.

Progesterone and calcitriol reduce invasive potential of endometrial cancer cells by targeting ARF6, NEDD9 and MT1-MMP.

PubMed

Waheed, Sana; Dorjbal, Batsukh; Hamilton, Chad A; Maxwell, G Larry; Rodriguez, Gustavo C; Syed, Viqar

2017-12-26

Previously, we have demonstrated that progesterone and calcitriol synergistically inhibit growth of endometrial and ovarian cancer by enhancing apoptosis and causing cell cycle arrest. Metastasis is the main reason of mortality in cancer patients. Activation of ADP-Ribosylation Factor 6 (ARF6), Neural Precursor cell expressed Developmentally Downregulated 9 (NEDD9), and Membrane-Type-1 Matrix Metalloproteinase (MT1-MMP) have been implicated in promoting tumor growth and metastasis. We examined the effects of progesterone, calcitriol and progesterone-calcitriol combination on metastasis promoting proteins in endometrial cancer. Expression of ARF6, NEDD9, and MT1-MMP was enhanced in advanced-stage endometrial tumors and in cancer cell lines compared to normal tissues and immortalized EM-E6/E7-TERT endometrial epithelial cells. Knockdown of these proteins significantly inhibited the invasiveness of the cancer cells. The expression levels of all three proteins was reduced with progesterone and progesterone-calcitriol combination treatment, whereas calcitriol alone showed no effect on their expression but moderately decreased MT1-MMP activity. Fluorescence microscopy showed membrane expression of MT1-MMP in vehicle and calcitriol-treated endometrial cancer cells. However, progesterone and calcitriol-progesterone combination treatment revealed MT1-MMP in the cytoplasm. Furthermore, progesterone and calcitriol reduced the activity of MT1-MMP, MMP-9, and MMP-2. In addition, invadopodia regulatory proteins were attenuated in both progesterone and progesterone-calcitriol combination treated cells as well as in MT1-MMP knockdown cells. Thus, targeting the aberrant MT1-MMP signaling with progesterone-calcitriol may be a novel approach to impede MT1-MMP mediated cancer dissemination and may have therapeutic benefits for endometrial cancer patients.

Racial Disparities in Recurrence Among Patients with Early Stage Endometrial Cancer: Is Recurrence Increased in Black Patients on Estrogen Replacement Therapy?: A Gynecologic Oncology Group Study

PubMed Central

Maxwell, G. Larry; Tian, Chunqiao; Risinger, John I; Hamilton, Chad A.; Barakat, Richard R.

2008-01-01

Objective Population-based studies suggest that Black women with localized endometrial cancer have shorter survival compared to White patients because of inequalities in treatment. The purpose of this investigation was to determine if there is a racial disparity in outcome between Black and White patients with early stage endometrial cancer treated similarly in a clinical trial setting. Methods A retrospective review of 110 Black and 1049 White patients with stage I and II endometrial cancer was performed using data from a randomized, placebo controlled trial performed by the Gynecologic Oncology Group (GOG) that evaluated postoperative estrogen replacement therapy (ERT) and the risk of cancer recurrence. Demographic, pathologic, treatment and outcome related data were collected and analyzed using regression and survival analysis. Results Estimates of recurrence-free survival (RFS) suggested that Black patients may be more likely to have disease recurrence, particularly those on ERT. Within a median follow-up of three years, 5 of 56 Black endometrial cancer patients in the ERT group were identified with recurrent disease compared to only 8 of 521 White patients. Adjusted for age, BMI and tumor grade, the relative risk of recurrence among Blacks in the ERT group was 11.2 (95% CI: 2.86-43.59, p=0.0005). Conclusions Our findings suggest that RFS may be shorter among Black women with stage I endometrial cancer, even in a clinical trials setting in which patients receive similar treatment and followup. This increased risk of recurrence appears to be most evident in Black women with endometrial cancer who maintain ERT following primary treatment. PMID:18698590

A prospective study of dietary acrylamide intake and the risk of breast, endometrial, and ovarian cancers

PubMed Central

Wilson, Kathryn M.; Mucci, Lorelei A.; Rosner, Bernard A.; Willett, Walter C.

2010-01-01

Background Acrylamide is a probable human carcinogen formed during cooking of many common foods. Epidemiological studies of acrylamide and breast cancer risk have been null; however, positive associations with ovarian and endometrial cancers have been reported. We studied acrylamide intake and risk of breast, endometrial, and ovarian cancers in a prospective cohort study. Methods We assessed acrylamide intake among 88,672 women in the Nurses’ Health Study using food frequency questionnaires administered every four years. Between 1980 and 2006 we identified 6301 cases of invasive breast cancer, 484 cases of invasive endometrial adenocarcinoma, and 416 cases of epithelial ovarian cancer. We used Cox proportional hazards models to study the association between acrylamide and cancer risk. Results We found no association between acrylamide intake and breast cancer overall or according to estrogen and progesterone receptor status. We found an increased risk of endometrial cancer among high acrylamide consumers (adjusted relative risk [RR] for highest versus lowest quintile=1.41, 95% CI: 1.01–1.97, p-value for trend=0.03). We observed a non-significant suggestion of increased risk for ovarian cancer overall (RR 1.25, CI: 0.88–1.77, p-trend=0.12), with a significantly increased risk for serous tumors (RR 1.58, CI: 0.99–2.52, p-trend=0.04). Associations did not differ by smoking status. Conclusions We observed no association between acrylamide and breast cancer. Risk of endometrial cancer and possibly ovarian cancer was greater among high acrylamide consumers. Impact This is the second prospective study to report positive associations with endometrial and ovarian cancers. These associations should be further evaluated to inform public health policy. PMID:20693310

Increased TET1 Expression in Inflammatory Microenvironment of Hyperinsulinemia Enhances the Response of Endometrial Cancer to Estrogen by Epigenetic Modulation of GPER

PubMed Central

Lv, Qiao-Ying; Xie, Bing-Ying; Yang, Bing-Yi; Ning, Cheng-Cheng; Shan, Wei-Wei; Gu, Chao; Luo, Xue-Zhen; Chen, Xiao-Jun; Zhang, Zhen-Bo; Feng, You-Ji

2017-01-01

Background: Insulin resistance (IR) has been well studied in the initiation and development of endometrial endometrioid carcinoma (EEC). As yet, it has been largely neglected for estrogen sensitivity in local endometrium in hyperinsulinemia-induced systemic microenvironment. The aim of this study was to investigate the role of insulin in regulating estrogen sensitivity and explore the potential mechanisms in insulin-driven inflammatory microenvironment. Methods: We first investigated the effect of insulin on estradiol-driven endometrial cancer cells proliferation in vitro to address the roles of insulin in modulating estrogen sensitivity. Then GPER, ERα and TET1 in EEC samples with or without insulin resistance were screened by immunohistochemistry to confirm whether insulin resistance regulates estrogen receptors. Further mechanism analysis was carried out to address whether TET1 was mediated epigenetic modulation of GPER in insulin-induced microenvironment. Results: Insulin enhanced estradiol-driven endometrial cancer cells proliferation by up-regulating G-protein-coupled estrogen receptor (GPER) expression, but not ERα or ERβ. Immunohistochemistry of EEC tissues showed that GPER expression was greatly increased in endometrial tissues from EEC subjects with insulin resistance and was positively correlated with Ten-eleven-translocation 1 (TET1) expression. Mechanistically, insulin up-regulates TET1 expression, and the latter, an important DNA hydroxymethylase, could up-regulate GPER expression through epigenetic modulation. Conclusion: This study identified TET1 as the upstream regulator of GPER expression and provides a possible mechanism that insulin-induced positive regulation of estrogen sensitivity in endometrial cancer cells. Increasing expression of GPER through TET1-mediated epigenetic modulation may emerge as the main regulator to enhance the response of endometrial cancer to estrogen in insulin-driven inflammatory microenvironment. PMID:28382153

Increased TET1 Expression in Inflammatory Microenvironment of Hyperinsulinemia Enhances the Response of Endometrial Cancer to Estrogen by Epigenetic Modulation of GPER.

PubMed

Lv, Qiao-Ying; Xie, Bing-Ying; Yang, Bing-Yi; Ning, Cheng-Cheng; Shan, Wei-Wei; Gu, Chao; Luo, Xue-Zhen; Chen, Xiao-Jun; Zhang, Zhen-Bo; Feng, You-Ji

2017-01-01

Background: Insulin resistance (IR) has been well studied in the initiation and development of endometrial endometrioid carcinoma (EEC). As yet, it has been largely neglected for estrogen sensitivity in local endometrium in hyperinsulinemia-induced systemic microenvironment. The aim of this study was to investigate the role of insulin in regulating estrogen sensitivity and explore the potential mechanisms in insulin-driven inflammatory microenvironment. Methods: We first investigated the effect of insulin on estradiol-driven endometrial cancer cells proliferation in vitro to address the roles of insulin in modulating estrogen sensitivity. Then GPER, ERα and TET1 in EEC samples with or without insulin resistance were screened by immunohistochemistry to confirm whether insulin resistance regulates estrogen receptors. Further mechanism analysis was carried out to address whether TET1 was mediated epigenetic modulation of GPER in insulin-induced microenvironment. Results: Insulin enhanced estradiol-driven endometrial cancer cells proliferation by up-regulating G-protein-coupled estrogen receptor (GPER) expression, but not ERα or ERβ. Immunohistochemistry of EEC tissues showed that GPER expression was greatly increased in endometrial tissues from EEC subjects with insulin resistance and was positively correlated with Ten-eleven-translocation 1 (TET1) expression. Mechanistically, insulin up-regulates TET1 expression, and the latter, an important DNA hydroxymethylase, could up-regulate GPER expression through epigenetic modulation. Conclusion: This study identified TET1 as the upstream regulator of GPER expression and provides a possible mechanism that insulin-induced positive regulation of estrogen sensitivity in endometrial cancer cells. Increasing expression of GPER through TET1-mediated epigenetic modulation may emerge as the main regulator to enhance the response of endometrial cancer to estrogen in insulin-driven inflammatory microenvironment.

Neonatal estrogenic exposure suppresses PTEN-related endometrial carcinogenesis in recombinant mice.

PubMed

Begum, Monjura; Tashiro, Hironori; Katabuchi, Hidetaka; Suzuki, Akira; Kurman, Robert J; Okamura, Hitoshi

2006-03-01

Human endometrial carcinomas, as well as complex atypical hyperplasias (CAH), are estrogen related and frequently have mutations in the PTEN gene. However, the mutual contribution of estrogen and PTEN mutations to endometrial carcinogenesis in vivo is unknown. To address this issue, we investigated whether neonatal estrogenic treatments augment the incidence of CAH and carcinomas in murine PTEN (mPTEN) heterozygous (+/-) mutant mice, an animal model for endometrial carcinoma. Low doses of diethylstilbestrol (1 ng/g/day), genistein (50 microg/g/day) in phytoestrogens, estriol (E(3)) (4 microg/g/day), and vehicle (ethanol and corn oil) were administered subcutaneously daily to neonatal pups from the 1st to 5th day after birth. At 52 weeks of age, the morphological changes in the endometrium, and uterine expression of Hoxa 10 and Hoxa 11, were evaluated. These Hoxa genes are abdominal B-type homeobox genes, which normally regulate differentiation of the Müllerian duct. The incidence of CAH and adenocarcinomas of the endometrium was significantly decreased by the neonatal estrogenic treatments in the mPTEN+/- mice. Coincidentally, all treatments significantly decreased the stromal cell density, and CAH and adenocarcinomas rarely developed in the epithelium adjacent to the affected endometrial stroma. Moreover, the uterine expression of Hoxa 10 in mice with neonatal genistein and E(3) treatments, and that of Hoxa 11 in mice with all treatments, was significantly lower when compared with vehicle alone. Taken together, neonatal estrogenic exposure induced stromal atrophy and/or hyalinization accompanied by repressed expression of Hoxa 10 and Hoxa 11, and exerted an inhibitory effect on PTEN-related tumorigenesis. These findings provide new insight into the interaction between endometrial epithelium and stroma in endometrial carcinogenesis in vivo.

Prostaglandin F2alpha-F-prostanoid receptor signaling promotes neutrophil chemotaxis via chemokine (C-X-C motif) ligand 1 in endometrial adenocarcinoma.

PubMed

Wallace, Alison E; Sales, Kurt J; Catalano, Roberto D; Anderson, Richard A; Williams, Alistair R W; Wilson, Martin R; Schwarze, Jurgen; Wang, Hongwei; Rossi, Adriano G; Jabbour, Henry N

2009-07-15

The prostaglandin F(2alpha) (PGF(2alpha)) receptor (FP) is elevated in endometrial adenocarcinoma. This study found that PGF(2alpha) signaling via FP regulates expression of chemokine (C-X-C motif) ligand 1 (CXCL1) in endometrial adenocarcinoma cells. Expression of CXCL1 and its receptor, CXCR2, are elevated in cancer tissue compared with normal endometrium and localized to glandular epithelium, endothelium, and stroma. Treatment of Ishikawa cells stably transfected with the FP receptor (FPS cells) with 100 nmol/L PGF(2alpha) increased CXCL1 promoter activity, mRNA, and protein expression, and these effects were abolished by cotreatment of cells with FP antagonist or chemical inhibitors of Gq, epidermal growth factor receptor, and extracellular signal-regulated kinase. Similarly, CXCL1 was elevated in response to 100 nmol/L PGF(2alpha) in endometrial adenocarcinoma explant tissue. CXCL1 is a potent neutrophil chemoattractant. The expression of CXCR2 colocalized to neutrophils in endometrial adenocarcinoma and increased neutrophils were present in endometrial adenocarcinoma compared with normal endometrium. Conditioned media from PGF(2alpha)-treated FPS cells stimulated neutrophil chemotaxis, which could be abolished by CXCL1 protein immunoneutralization of the conditioned media or antagonism of CXCR2. Finally, xenograft tumors in nude mice arising from inoculation with FPS cells showed increased neutrophil infiltration compared with tumors arising from wild-type cells or following treatment of mice bearing FPS tumors with CXCL1-neutralizing antibody. In conclusion, our results show a novel PGF(2alpha)-FP pathway that may regulate the inflammatory microenvironment in endometrial adenocarcinoma via neutrophil chemotaxis.

Isolation and characterization of equine endometrial mesenchymal stromal cells.

PubMed

Rink, B Elisabeth; Amilon, Karin R; Esteves, Cristina L; French, Hilari M; Watson, Elaine; Aurich, Christine; Donadeu, F Xavier

2017-07-12

Equine mesenchymal stromal/stem cells (MSCs) are most commonly harvested from bone marrow (BM) or adipose tissue, requiring the use of surgical procedures. By contrast, the uterus can be accessed nonsurgically, and may provide a more readily available cell source. While human endometrium is known to harbor mesenchymal precursor cells, MSCs have not been identified in equine endometrium. This study reports the isolation, culture, and characterization of MSCs from equine endometrium. The presence of MSC and pericyte markers in endometrial sections was determined using immunohistochemistry. Stromal cells were harvested and cultured after separation of epithelial cells from endometrial fragments using Mucin-1-bound beads. For comparison, MSCs were also harvested from BM. The expression of surface markers in endometrial and BM-derived MSCs was characterized using flow cytometry and quantitative polymerase chain reaction. MSCs were differentiated in vitro into adipogenic, chondrogenic, osteogenic, and smooth muscle lineages. Typical markers of MSCs (CD29, CD44, CD90, and CD105) and pericytes (NG2 and CD146) were localized in the equine endometrium. Both endometrial and BM MSCs grew clonally and robustly expressed MSC and pericyte markers in culture while showing greatly reduced or negligible expression of hematopoietic markers (CD45, CD34) and MHC-II. Additionally, both endometrial and BM MSCs differentiated into adipogenic, osteogenic, and chondrogenic lineages in vitro, and endometrial MSCs had a distinct ability to undergo smooth muscle differentiation. We have demonstrated for the first time the presence of cells in equine endometrium that fulfill the definition of MSCs. The equine endometrium may provide an alternative, easily accessible source of MSCs, not only for therapeutic regeneration of the uterus, but also for other tissues where MSCs from other sources are currently being used therapeutically.

Prostaglandin F2α–F-Prostanoid Receptor Signalling Promotes Neutrophil Chemotaxis via Chemokine (CXC motif) Ligand-1 in Endometrial Adenocarcinoma

PubMed Central

Wallace, Alison E; Sales, Kurt J; Catalano, Roberto D; Anderson, Richard A; Williams, Alistair RW; Wilson, Martin R; Schwarze, Jurgen; Wang, Hongwei; Rossi, Adriano G; Jabbour, Henry N

2009-01-01

The prostaglandin F2α (PGF2α) receptor (FP) is elevated in endometrial adenocarcinoma. This study found that PGF2α signalling via FP regulates expression of chemokine (C-X-C motif) ligand 1 (CXCL1) in endometrial adenocarcinoma cells. Expression of CXCL1 and its receptor, CXCR2, are elevated in cancer tissue as compared to normal endometrium and localised to glandular epithelium, endothelium and stroma. Treatment of Ishikawa cells stably transfected with the FP receptor (FPS cells) with 100nM PGF2α increased CXCL1 promoter activity, mRNA and protein expression, and these effects were abolished by co-treatment of cells with FP antagonist or chemical inhibitors of Gq, EGFR and ERK. Similarly, CXCL1 was elevated in response to 100 nM PGF2α in endometrial adenocarcinoma explant tissue. CXCL1 is a potent neutrophil chemoattractant. The expression of CXCR2 colocalised to neutrophils in endometrial adenocarcinoma and increased neutrophils were present in endometrial adenocarcinoma compared with normal endometrium. Conditioned media from PGF2α-treated FPS cells stimulated neutrophil chemotaxis which could be abolished by CXCL1 protein immunoneutralisation of the conditioned media or antagonism of CXCR2. Finally, xenograft tumours in nude mice arising from inoculation with FPS cells showed increased neutrophil infiltration compared to tumours arising from wild-type cells or following treatment of mice bearing FPS tumours with CXCL1-neutralising antibody. In conclusion, our results demonstrate a novel PGF2α-FP pathway that may regulate the inflammatory microenvironment in endometrial adenocarcinoma via neutrophil chemotaxis. PMID:19549892

High Glucose-Mediated STAT3 Activation in Endometrial Cancer Is Inhibited by Metformin: Therapeutic Implications for Endometrial Cancer

PubMed Central

Wallbillich, John J.; Josyula, Srirama; Saini, Uksha; Zingarelli, Roman A.; Dorayappan, Kalpana Deepa Priya; Riley, Maria K.; Wanner, Ross A.; Cohn, David E.; Selvendiran, Karuppaiyah

2017-01-01

Objectives STAT3 is over-expressed in endometrial cancer, and diabetes is a risk factor for the development of type 1 endometrial cancer. We therefore investigated whether glucose concentrations influence STAT3 expression in type 1 endometrial cancer, and whether such STAT3 expression might be inhibited by metformin. Methods In Ishikawa (grade 1) endometrial cancer cells subjected to media with low, normal, or high concentrations of glucose, expression of STAT3 and its target proteins was evaluated by real-time quantitative PCR (qPCR). Ishikawa cells were treated with metformin and assessed with cell proliferation, survival, migration, and ubiquitin assays, as well as Western blot and qPCR. Expression of apoptosis proteins was evaluated with Western blot in Ishikawa cells transfected with a STAT3 overexpression plasmid and treated with metformin. A xenograft tumor model was used for studying the in vivo efficacy of metformin. Results Expression of STAT3 and its target proteins was increased in Ishikawa cells cultured in high glucose media. In vitro, metformin inhibited cell proliferation, survival and migration but induced apoptosis. Metformin reduced expression levels of pSTAT3 ser727, total STAT3, and its associated cell survival and anti-apoptotic proteins. Additionally, metformin treatment was associated with increased degradation of pSTAT3 ser727. No change in apoptotic protein expression was noticed with STAT3 overexpression in Ishikawa cells. In vivo, metformin treatment led to a decrease in tumor weight as well as reductions of STAT3, pSTAT3 ser727, its target proteins. Conclusions These results suggest that STAT3 expression in type 1 endometrial cancer is stimulated by a high glucose environment and inhibited by metformin. PMID:28114390

Effect of steroid treatment of endometrial cells on blastocyst development during co-culture.

PubMed

Goff, A K; Smith, L C

1998-04-01

The objective of this study was to determine if treatment of endometrial cells with progesterone or progesterone plus estradiol would improve the development of bovine embryos to the blastocyst stage during co-culture. After IVF, bovine embryos were cultured with oviduct epithelial cells for 3 d. In Experiment 1 the embryos were cultured with a) oviduct epithelial cells; b) endometrial epithelial cells (EEC); c) EEC with 10 ng/ml progesterone (EEC + P); or d) EEC with 10 ng/ml progesterone and 10 pg/ml estradiol (EEC + PE) for 6 d. In Experiment 2 the embryos were cultured with a) oviduct epithelial cells; b) endometrial stromal cells (ESC); c) ESC with 10 ng/ml progesterone (ESC + P); or d) ESC with 10 ng/ml progesterone and 10 pg/ml estradiol (ESC + PE) for 6 d. Results from Experiment 1 showed that endometrial epithelial cells supported development to the blastocyst stage as effectively as the oviduct cells; however, the size of the blastocysts was smaller for the endometrial cells. There was no effect of steroid hormone treatment on development to the blastocyst stage or on the size of the blastocysts. Results from Experiment 2 showed that stromal cells supported development to the blastocyst stage as effectively as oviduct cells. The hatching rate was lower when the embryos were co-cultured with stromal cells than oviduct epithelial cells; but there was no effect of steroid treatment. These data show that untreated endometrial epithelial cells are as effective as oviduct cells in maintaining embryo development to the blastocyst stage. However, embryo development was not improved by steroid treatment of the cells.

Frequent PIK3CA Mutations in Colorectal and Endometrial Cancer with Double Somatic Mismatch Repair Mutations

PubMed Central

Cohen, Stacey A.; Turner, Emily H.; Beightol, Mallory B.; Jacobson, Angela; Gooley, Ted A.; Salipante, Stephen J.; Haraldsdottir, Sigurdis; Smith, Christina; Scroggins, Sheena; Tait, Jonathan F.; Grady, William M.; Lin, Edward H.; Cohn, David E.; Goodfellow, Paul J.; Arnold, Mark W.; de la Chapelle, Albert; Pearlman, Rachel; Hampel, Heather; Pritchard, Colin C.

2016-01-01

Background & Aims Double somatic mutations in mismatch repair (MMR) genes have recently been described in colorectal and endometrial cancers with microsatellite instability (MSI) not attributable to MLH1 hypermethylation or germline mutation. We sought to define the molecular phenotype of this newly recognized tumor subtype. Methods From two prospective Lynch syndrome screening studies, we identified patients with colorectal and endometrial tumors harboring ≥2 somatic MMR mutations, but normal germline MMR testing (“double somatic”). We determined the frequencies of tumor PIK3CA, BRAF, KRAS, NRAS, and PTEN mutations by targeted next-generation sequencing and used logistic-regression models to compare them to: Lynch syndrome, MLH1 hypermethylated, and microsatellite stable (MSS) tumors. We validated our findings using independent datasets from The Cancer Genome Atlas (TCGA). Results Among colorectal cancer cases, we found that 14/21 (67%) of double somatic cases had PIK3CA mutations vs. 4/18 (22%) Lynch syndrome, 2/10 (20%) MLH1 hypermethylated, and 12/78 (15%) MSS tumors; p<0.0001. PIK3CA mutations were detected in 100% of 13 double somatic endometrial cancers (p=0.04). BRAF mutations were absent in double somatic and Lynch syndrome colorectal tumors. We found highly similar results in a validation cohort from TCGA (113 colorectal, 178 endometrial cancer), with 100% of double somatic cases harboring a PIK3CA mutation (p<0.0001). Conclusions PIK3CA mutations are present in double somatic mutated colorectal and endometrial cancers at substantially higher frequencies than other MSI subgroups. PIK3CA mutation status may better define an emerging molecular entity in colorectal and endometrial cancers, with the potential to inform screening and therapeutic decision making. PMID:27302833

Progesterone and calcitriol reduce invasive potential of endometrial cancer cells by targeting ARF6, NEDD9 and MT1-MMP

PubMed Central

Waheed, Sana; Dorjbal, Batsukh; Hamilton, Chad A.; Maxwell, G. Larry; Rodriguez, Gustavo C.; Syed, Viqar

2017-01-01

Previously, we have demonstrated that progesterone and calcitriol synergistically inhibit growth of endometrial and ovarian cancer by enhancing apoptosis and causing cell cycle arrest. Metastasis is the main reason of mortality in cancer patients. Activation of ADP-Ribosylation Factor 6 (ARF6), Neural Precursor cell expressed Developmentally Downregulated 9 (NEDD9), and Membrane-Type-1 Matrix Metalloproteinase (MT1-MMP) have been implicated in promoting tumor growth and metastasis. We examined the effects of progesterone, calcitriol and progesterone-calcitriol combination on metastasis promoting proteins in endometrial cancer. Expression of ARF6, NEDD9, and MT1-MMP was enhanced in advanced-stage endometrial tumors and in cancer cell lines compared to normal tissues and immortalized EM-E6/E7-TERT endometrial epithelial cells. Knockdown of these proteins significantly inhibited the invasiveness of the cancer cells. The expression levels of all three proteins was reduced with progesterone and progesterone-calcitriol combination treatment, whereas calcitriol alone showed no effect on their expression but moderately decreased MT1-MMP activity. Fluorescence microscopy showed membrane expression of MT1-MMP in vehicle and calcitriol-treated endometrial cancer cells. However, progesterone and calcitriol-progesterone combination treatment revealed MT1-MMP in the cytoplasm. Furthermore, progesterone and calcitriol reduced the activity of MT1-MMP, MMP-9, and MMP-2. In addition, invadopodia regulatory proteins were attenuated in both progesterone and progesterone-calcitriol combination treated cells as well as in MT1-MMP knockdown cells. Thus, targeting the aberrant MT1-MMP signaling with progesterone-calcitriol may be a novel approach to impede MT1-MMP mediated cancer dissemination and may have therapeutic benefits for endometrial cancer patients. PMID:29371931

Clinicopathological Spectrum of Endometrial Changes in Peri-menopausal and Post-menopausal Abnormal Uterine Bleeding: A 2 Years Study.

PubMed

Damle, Rajshri P; Dravid, N V; Suryawanshi, Kishor H; Gadre, Arundhati S; Bagale, Priya S; Ahire, Neelam

2013-12-01

Abnormal uterine bleeding is the Common presenting complaint in Gynaecology Outpatient Department in all age groups. It is due to the anovulatory cycles which are commonly seen in adolescent and peri-menopausal women. Abnormal uterine bleeding is caused by wide variety of organic or non-organic causes. Histopathological examination of endometrial sample remains the gold standard for diagnosis of endometrial pathology. To study the clinicopathological spectrum of endometrium in abnormal uterine bleeding in peri-menopausal and post-menopausal age groups. The study included prospective analysis of 119 cases of endometrial samples in patients of abnormal uterine bleeding above 40 years of age. The specimens were routinely processed and H&E stained slides were studied. Patients were categorized into peri-menopausal (40-49 years) and post-menopausal (> 50 years) age group. A total of 119 specimens of endometrium were analyzed. Maximum number (73.94%) of cases were from peri-menopausal age group. The most common presenting complaint was menorrhagia (48.86%) followed by post-menopausal bleeding (26.05%). In peri-menopausal age group proliferative endometrium (35.22%) was the predominant histopathological pattern followed by endometrial hyperplasia (23.86%). Atrophic endometrium (25.80%) was the most frequent finding followed by endometrial hyperplasia (19.35%) in post-menopausal age group. Three cases of endometrial carcinoma were reported in post-menopausal age group only. A thorough histopathological work up and clinical correlation is mandatory in cases of abnormal uterine bleeding above the age of 40 years to find out organic lesions. Careful screening can detect early cancer of endometrium which has excellent prognosis and it will help in further management.

Increased endometrial thickness in women with hypertension.

PubMed

Bornstein, J; Auslender, R; Goldstein, S; Kohan, R; Stolar, Z; Abramovici, H

2000-09-01

We noticed an increase in endometrial thickness in women with hypertension who were treated with a combination of medications, including beta-blockers. The purpose of this study was to examine whether the endometrium of hypertensive women is thicker than that of healthy women and to determine whether endometrial thickening in hypertensive women is directly related to the antihypertensive beta-blocker treatment. We compared 3 groups of postmenopausal patients as follows: (1) women with a history of essential hypertension treated with a combination of medications, including beta-blockers; (2) women with a history of hypertension treated with a combination of medications that did not include beta-blockers; and (3) healthy women without hypertension. All patients were interviewed and examined, blood tests were performed, and endometrial thickness in the anterior-posterior diameter was measured by vaginal ultrasonography. Among the exclusion criteria were diabetes or an abnormal fasting blood glucose level, obesity, hormonal medication or replacement hormonal therapy during the previous 6 months, and a history of hormonal disturbances, infertility, or polycystic ovary syndrome. Of 45 hypertensive women enrolled in the study, 22 were treated with a beta-blocker combination medication and 23 were treated with other antihypertensive medications. They were compared with 25 healthy women. There was no statistically significant difference in endometrial thickness between women treated with medications, including beta-blockers, and those who were treated with other hypotensive agents. Twenty percent of women with hypertension and none of the healthy women had endometrium >5 mm thick (P <.017; odds ratio, 8.22; 95% confidence interval, 1.22-infinity). Twenty percent of hypertensive postmenopausal women were found to have increased endometrial thickness. However, we were unable to substantiate an association between the type of treatment administered, whether beta-blockers were included, and the increase in endometrial thickness.

Gonadal steroids regulate the expression of aggrecanases in human endometrial stromal cells in vitro.

PubMed

Wen, Jiadi; Zhu, Hua; Leung, Peter C K

2013-10-01

The human endometrium undergoes cyclic change during each menstrual cycle in response to gonadal steroids. Proteolysis of endometrial extracellular matrix (ECM) is necessary to prepare this dynamic tissue for pregnancy. Proteolytic enzymes such as matrix metalloproteinase (MMP) and closely related a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) have been assigned key roles in the highly regulated cyclic remodelling of the endometrial ECM. We have previously shown that ADAMTS-1 undergoes spatiotemporal changes in human endometrial stromal cells under the regulation of gonadal steroids. This suggests that other ADAMTS subtypes, known as aggrecanases, may contribute to the ECM remodelling events that occur in female physiological cycles and in preparation for pregnancy. To determine whether progesterone (P4), 17β-estradiol (E2), or dihydrotestosterone (DHT), alone or in combination, are capable of regulating ADAMTS-4, -5, -8 or -9 expression in human endometrial stromal cells in vitro. Real-time quantitative PCR and Western blot analysis were used to measure ADAMTSs mRNA and protein levels in primary cultures of human endometrial stromal cells (n = 12). P4, DHT but not E2 have regulatory effects on ADAMTS-8, -9 and -5 expression. Combined treatment with gonadal steroids did not show any synergistic or antagonistic effects. However, the synthetic steroid antagonists RU486 and hydroxyflutamide specifically inhibited the P4- or DHT-mediated regulatory effects on ADAMTS expression. These studies provide evidence that the regulation of aggrecanases by gonadal steroids in human endometrial stromal cells may play an important role during decidualization. © 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Ultrasound Scoring of Endometrial Pattern for Fast-Track Identification or Exclusion of Endometrial Cancer in Women with Postmenopausal Bleeding.

PubMed

Dueholm, Margit; Hjorth, Ina Marie Dueholm; Dahl, Katja; Hansen, Estrid Stær; Ørtoft, Gitte

2018-06-23

To evaluate the Risk of Endometrial Cancer (REC) scoring system for the prediction of high and low probability of endometrial cancer (EC) in women with postmenopausal bleeding (PMB). Prospective study (Canadian Task Force classification II-1). Academic hospital. Nine hundred and fifty consecutive patients with PMB underwent transvaginal ultrasonography (TVS) and REC scoring between November 2013 and December 2015. Obstetrics and gynecology residents, supervised by trained physicians, scored endometrial patterns according to the previously established REC scoring system. The reference standard was endometrial samples, endometrial thickness (ET; 4-4.9 mm), operative hysteroscopy, or hysterectomy (ET ≥5 mm), and one-year follow-up in all patients presenting with ET <4 mm. Diagnostic performance for prediction of probability of malignancy was assessed using the REC scoring system. The area under the receiver operating characteristic (ROC) curve (AUC) of the TVS REC score system was 97% (range: 95-98) for prediction of malignancy. In 656 patients with ET ≥4 mm, REC scoring effectively predicted high probability of malignancy: sensitivity (95% confidence interval): 92% (range: 87%-95%); specificity: 94% (range: 91%-96%). An REC score of 0 was present in 206 (32%) patients with ET ≥4 mm and was associated with a low negative likelihood ratio of 0.026 for EC. Only 7 patients with EC/atypical hyperplasia were seen among these 206 patients. The REC scoring system identified or ruled out most ECs, clearly demonstrating that more specific image analysis at first-line TVS can accelerate the diagnosis of EC in patients with PMB and may allow for improved selection of second-line strategies in patients with ET ≥4 mm. Copyright © 2018. Published by Elsevier Inc.

Effect of sildenafil citrate on endometrial preparation and outcome of frozen-thawed embryo transfer cycles: a randomized clinical trial.

PubMed

Dehghani Firouzabadi, Razieh; Davar, Robab; Hojjat, Farzaneh; Mahdavi, Mohamad

2013-02-01

Sildenafil citrate may increase endometrial thickness and affect the outcome of frozen-thawed embryo transfer cycles. The aim of this study was to estimate the effect of sildenafil citrate on ultrasonographic endometrial thickness and pattern and to investigate the estrogen level on the day of progesterone administration, the implantation rate and chemical pregnancy rate in frozen embryo transfer cycles. This randomized controlled trial was conducted on 80 patients who had an antecedent of poor endometrial response and frozen embryos. 40 patients were given estradiol by a step up method with menstruation to prepare the endometrium, and the other 40 were given sildenafil citrate tablets (50 mg) daily in addition to the above treatment protocol from the first day of the cycle until the day progesterone was started. This was discontinued 48-72 hours prior to the embryo transfer. The endometrial thickness was significantly higher in the sildenafil citrate group (p<0.0001), the triple line patterns of the endometrium were significantly higher in the sildenafil citrate group (p<0.0001), while the intermediate patterns of the endometrium were not significantly different in the two groups. The echogen patterns of the endometrium were significantly higher in control group (p<0.0001). Finally, implantation rate and the chemical pregnancy rates were higher in the sildenafil citrate group but not significantly. As our study shows, the oral use of sildenafil citrate is a good way to improve the endometrial receptivity. We recommend the routine use of oral sildenafil citrate in patients with a previous failure of assisted reproduction technology cycles due to poor endometrial thickness.

Clinical statistics of gynecologic cancers in Japan.

PubMed

Yamagami, Wataru; Nagase, Satoru; Takahashi, Fumiaki; Ino, Kazuhiko; Hachisuga, Toru; Aoki, Daisuke; Katabuchi, Hidetaka

2017-03-01

Cervical, endometrial, and ovarian cancers, have both high morbidity and mortality among the gynecologic malignant tumors in Japan. The present study was conducted using both the population-based cancer registry and the gynecologic cancer registry to elucidate the characteristics of gynecologic malignant tumors in Japan. Based on nationwide estimates from the population-based cancer registry in Japan, the morbidities and mortality of cervical, endometrial, and ovarian cancers were obtained and used for analysis. Clinicopathologic factors for cervical cancer, endometrial cancer, ovarian cancer, including age, clinical stage, postsurgical stage, histological type, therapeutic strategy, and prognosis were retrieved from the gynecologic cancer registry published by the Japan Society of Obstetrics and Gynecology and used for analysis. The morbidities of cervical, endometrial, and ovarian cancers were 10,908, 13,606, and 9,384 women in 2012, respectively. The prevalence of endometrial cancer has significantly and consistently been increasing and represents the most common gynecologic malignant tumor in Japan. The mortalities of cervical, endometrial, and ovarian cancers were 2.1, 1.3, and 3.2 per 100,000 in 2012, respectively. In 2014, 52.2% of cervical cancer patients were classified as stage I, 22.5% as stage II, 10.2% as stage III, and 11.2% as stage IV. In addition, 71.9% of endometrial cancer patients were classified as stage I, 6.0% as stage II, 13.3% as stage III, and 7.5% as stage IV. Finally, 43.2% of ovarian cancer patients were classified as stage I, 9.1% as stage II, 27.6% as stage III, and 7.2% as stage IV. Twelve-point six percent of ovarian cancer patients received neoadjuvant chemotherapy. Copyright © 2017. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Endometrial cancer: correlation of apparent diffusion coefficient (ADC) with tumor cellularity and tumor grade.

PubMed

Kishimoto, Keiko; Tajima, Shinya; Maeda, Ichiro; Takagi, Masayuki; Ueno, Takahiko; Suzuki, Nao; Nakajima, Yasuo

2016-08-01

Diffusion-weighted imaging (DWI) and the apparent diffusion coefficient (ADC) are widely used for detecting uterine endometrial cancer. The relationships between ADC values and pathological features of endometrial cancer have not yet been established. To investigate whether ADC values of endometrial cancer vary according to histologic tumor cellularity and tumor grade. We retrospectively reviewed 30 pathologically confirmed endometrial cancers. All patients underwent conventional non-enhanced magnetic resonance imaging (MRI) and DWI procedures, and ADC values were calculated. Tumor cellularity was evaluated by counting cancer cells in three high-power ( × 400) fields. The correlation between ADC values and tumor cellularity was assessed using Pearson's correlation coefficient test for statistical analysis. The mean ± standard deviation (SD) ADC value ( ×10(-3) mm(2)/s) of endometrial cancer was 0.85 ± 0.22 (range, 0.55-1.71). The mean ± SD tumor cellularity was 528.36 ± 16.89 (range, 298.0-763.6). ADC values were significantly inversely correlated with tumor cellularity. No significant relationship was observed between ADC values and tumor grade (mean ADC values: G1, 0.88 ± 0.265 × 10(-3) mm(2)/s; G2, 0.80 ± 0.178 × 10(-3) mm(2)/s; G3, 0.81 ± 0.117 × 10(-3) mm(2)/s). There is a significant inverse relationship between ADC values and tumor cellularity in endometrial cancer. No significant differences in average ADC value were observed between G1, G2, and G3 tumors. However, the lower the tumor grade, the wider the SD. © The Foundation Acta Radiologica 2015.

Evaluation and validation of the diagnostic value of the apparent diffusion coefficient for differentiating early-stage endometrial carcinomas from benign mimickers at 3T MRI.

PubMed

Wang, Xue; Zhao, Yu; Hu, Yumin; Zhou, Yongjin; Ye, Xinjian; Liu, Kun; Bai, Guanghui; Guo, Anna; Du, Meimei; Jiang, Lezhen; Wang, Jinhong; Yan, Zhihan

2017-07-11

Previous researchers obtained various apparent diffusion coefficient (ADC) cutoff values to differentiate endometrial carcinoma from benign mimickers with 1.5T magnetic resonance imaging (MRI). Few studies have used 3T MRI or validated the effectiveness of these cutoff ADC values prospectively. This study was designed in two stages to obtain a cutoff ADC value at 3T MRI and to validate prospectively the role of the ADC value. First, we conducted a retrospective study of 60 patients to evaluate the diagnostic value of ADC by obtain a theoretical cutoff ADC value for differentiating between benign and malignant endometrial lesions. Student's t test revealed that ADC values for stage I endometrial carcinomas were significantly lower than those for benign lesions. The area under the curve value of the receiver operating characteristic curve was 0.993, and the cutoff ADC value was 0.98 × 10-3 mm2/s. The sensitivity, specificity, and overall accuracy of diagnosing stage I endometrial carcinoma were 100%, 97.1%, and 98.3%, respectively. Second, we conducted a prospective study of 26 patients to validate the use of the cutoff ADC value obtained in the study's first stage. The sensitivity, specificity, and overall accuracy for differentiating malignant from benign endometrial lesions based on the cutoff ADC value obtained earlier were as follows: radiologist 1 attained 86.67%, 100.0%, and 92.31%, respectively; radiologist 2 attained 86.67%, 91.0%, and 88.5%, respectively. Our results suggest that ADC values could be a potential biomarker for use as a quantitative and qualitative tool for differentiating between early-stage endometrial carcinomas and benign mimickers.

Loss of switch/sucrose non-fermenting complex protein expression is associated with dedifferentiation in endometrial carcinomas

PubMed Central

Karnezis, Anthony N.; Hoang, Lien N.; Coatham, Mackenzie; Ravn, Sarah; Almadani, Noorah; Cloutier, Basile; Irving, Julie; Meng, Bo; Li, Xiaodong; Chow, Christine; McAlpine, Jessica; Kuo, Kuan-Ting; Mao, Tsui-Lien; Djordjevic, Bojana; Soslow, Robert A.; Huntsman, David G.; Gilks, C. Blake; Köbel, Martin; Lee, Cheng-Han

2016-01-01

Dedifferentiated endometrial carcinoma is an aggressive type of endometrial cancer that contains a mix of low grade endometrioid and undifferentiated carcinoma components. We performed targeted sequencing of 8 dedifferentiated endometrial carcinomas and identified somatic frameshift/nonsense mutations in SMARCA4, a core member of the switch/sucrose non-fermenting (SWI/SNF) complex, in the undifferentiated components of 4 tumors. Immunohistochemical analysis confirmed the loss of SMARCA4 in the undifferentiated component of these 4 SMARCA4-mutated cases while the corresponding low grade endometrioid component showed retained SMARCA4 expression. An expanded survey of another member of the SWI/SNF complex showed SMARCB1 loss in the undifferentiated component of 2 SMARCA4-intact tumors. Subsequent immunohistochemical analysis of SMARCA4 and SMARCB1 was done in an additional set of 22 centrally reviewed dedifferentiated endometrial carcinomas and 31 grade 3 endometrioid carcinomas. Combining the results from the index and the expansion set, 15 of 30 (50%) of the dedifferentiated endometrial carcinomas examined showed either SMARCA4 loss (37%) or SMARCB1 loss (13%). The loss of SMARCA4 or SMARCB1 was mutually exclusive and occurred only in the undifferentiated component. All 31 grade 3 endometrioid carcinomas showed intact SMARCA4/SMARCB1 expression. The majority (73%) of the SMARCA4-deficient and half of SMARCB1-deficient undifferentiated component developed in a mismatch repair protein (MMR)-deficient molecular context. The observed spatial association between SMARCA4/SMARCB1 loss and histologic dedifferentiation suggests that loss of these SWI/SNF complex proteins may contribute to the development of dedifferentiated endometrial carcinoma. PMID:26743474