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  1. Endometrial ablation

    MedlinePlus

    Hysteroscopy-endometrial ablation; Laser thermal ablation; Endometrial ablation-radiofrequency; Endometrial ablation-thermal balloon ablation; Rollerball ablation; Hydrothermal ablation; Novasure ablation

  2. 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

  3. Endometrial cancer

    MedlinePlus

    ... therapy , and chemotherapy . Surgery to remove the uterus ( hysterectomy ) may be done in women with early stage ... uterine; Cancer - endometrial; Uterine corpus cancer Patient Instructions Hysterectomy - abdominal - discharge Hysterectomy - laparoscopic - discharge Hysterectomy - vaginal - discharge ...

  4. Endometrial polyps

    MedlinePlus

    ... cancer is higher if you are postmenopausal, on Tamoxifen, or have heavy or irregular periods. These factors may increase the risk for endometrial polyps: Obesity Tamoxifen, a treatment for breast cancer Postmenopausal hormone replacement ...

  5. 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

  6. Endometrial hyperplasia.

    PubMed

    Mills, Anne M; Longacre, Teri A

    2010-11-01

    Endometrial hyperplasia is a heterogeneous set of pathologic lesions that range from mild, reversible glandular proliferations to direct cancer precursors. These lesions comprise a continuum of morphologic appearances, with the earliest proliferation represented by crowded glands with simple tubular architecture lined by cells resembling proliferative endometrium, whereas advanced proliferations in this continuum are characterized by crowded glands with complex architecture, often containing cells with nuclear atypia resembling low-grade endometrioid adenocarcinoma. The former "early" proliferations may be isolated to an endometrial polyp, but advanced proliferations are generally more diffusely present throughout the endometrium. There are at least three major classification systems for endometrial carcinoma precursor lesions, each of which trend toward overlap at the complex end of the spectrum. Although some classifications are based on a series of molecular genetic alterations (which may or may not translate into biologically or clinically relevant risk lesions), each classification scheme ultimately uses a series of histologic features, usually a combination of architecture and cytology, to establish a diagnosis of hyperplasia. Because different pathologists may apply different histologic criteria for endometrial hyperplasia depending on the classification system used, this article will provide an overview of the classifications used in current daily practice, present the histologic criteria and relative merits of each classification system, and discuss common and not so common causes of misclassification.

  7. Dalantercept in Treating Patients With Recurrent or Persistent Endometrial Cancer

    ClinicalTrials.gov

    2017-05-03

    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

  8. Copanlisib in Treating Patients With Persistent or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2017-01-20

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

  9. Endometrial receptivity: evaluation with ultrasound.

    PubMed

    Bonilla-Musoles, Fernando; Raga, Francisco; Osborne, Newton G; Castillo, Juan Carlos; Bonilla, Francisco

    2013-03-01

    An adequate endometrial receptivity is a crucial factor for embryo implantation. We describe endometrial morphology (endometrial appearance or pattern, endometrial thickness, volume, and delimitation), based on the concepts and possibilities of the new ultrasound modalities (3-dimensional/4-dimensional ultrasound, automatic volume calculation, virtual organ computer-aided analysis, tomographic ultrasound image, inverse mode, and 3-dimensional Doppler angiography) as markers of endometrial receptivity.

  10. Obesity and Endometrial Cancer.

    PubMed

    Shaw, Eileen; Farris, Megan; McNeil, Jessica; Friedenreich, Christine

    Endometrial cancer is the sixth most common cancer in women worldwide and the most common gynecologic malignancy in the developed world. This chapter explores the current epidemiologic evidence on the association between obesity and endometrial cancer risk and mortality. Using body mass index (BMI) as a measure of obesity, we found that obesity (defined as BMI > 30 and < 35 kg/m(2)) was associated with a 2.6-fold increase in endometrial cancer risk, while severe obesity (BMI > 35 kg/m(2)) was associated with a 4.7-fold increase compared to normal-weight women (BMI < 25 kg/m(2)). Increased central adiposity also increased endometrial cancer risk by 1.5- to twofold. Among both healthy and endometrial cancer patient populations, obesity was associated with a roughly twofold increase in endometrial cancer-specific mortality. This risk reduction was also observed for obesity and all-cause mortality among endometrial cancer patients. In the few studies that assessed risk associated with weight change, an increased endometrial cancer risk with weight gain and weight cycling was observed, whereas some evidence for a protective effect of weight loss was found. Furthermore, early-life obesity was associated with a moderately increased risk of endometrial cancer later in life. There are several mechanisms whereby obesity is hypothesized to increase endometrial cancer risk, including increased endogenous sex steroid hormones, insulin resistance, chronic inflammation and adipokines. Further research should focus on histological subtypes or molecular phenotypes of endometrial tumors and population subgroups that could be at an increased risk of obesity-associated endometrial cancer. Additionally, studies on weight gain, loss or cycling and weight loss interventions can provide mechanistic insight into the obesity-endometrial cancer association. Sufficient evidence exists to recommend avoiding obesity to reduce endometrial cancer risk.

  11. Temsirolimus in Treating Patients With Metastatic or Locally Advanced Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2015-02-05

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Recurrent Endometrial Carcinoma; Stage IIIA Endometrial Carcinoma; Stage IIIB Endometrial Carcinoma; Stage IIIC Endometrial Carcinoma; Stage IVA Endometrial Carcinoma; Stage IVB Endometrial Carcinoma

  12. Trebananib in Treating Patients With Persistent or Recurrent Endometrial Cancer

    ClinicalTrials.gov

    2017-08-23

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

  13. Trametinib With or Without GSK2141795 in Treating Patients With Recurrent or Persistent Endometrial Cancer

    ClinicalTrials.gov

    2017-09-11

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

  14. Nintedanib in Treating Patients With Recurrent or Persistent Endometrial Cancer

    ClinicalTrials.gov

    2016-10-26

    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

  15. Defective endometrial receptivity.

    PubMed

    Revel, Ariel

    2012-05-01

    The endometrium is one of the most fascinating tissues in the human body. Its sole purpose is to enable implantation of an embryo during a relatively short window of opportunity in the menstrual cycle. It is becoming clear that overcoming the current bottleneck in improvements to assisted reproductive techniques will require a closer look at the interface between uterus and embryo. Indeed, embryo implantation requires a cross talk with a receptive endometrium. Using sonography, hysteroscopy and endometrial biopsy we can learn about anatomical and functional markers of endometrial receptivity. This article reviews the factors which might cause defective endometrial receptivity. These include uterine polyps, septa, leiomyomata and adhesions. The effect of thin endometrium, endometriosis and hydrosalpinx is also described. Finally contemporary investigation of molecular markers of endometrial receptivity is described. Improving embryo implantation by a closer look inside the uterus is the key to increasing pregnancy rates in IVF.

  16. Endometrial Cancer Screening

    MedlinePlus

    ... Transvaginal ultrasound Endometrial sampling Tests are used to screen for different types of cancer. Some screening tests ... endometrium by inserting a brush, curette , or thin, flexible tube through the cervix and into the uterus. ...

  17. Endometrial Ablation for Menorrhagia

    PubMed Central

    Sanders, Barry H.

    1992-01-01

    Endometrial ablation is a relatively new treatment for patients with persistent menorrhagia. The procedure can be performed by either laser photocoagulation or electrocoagulation; both have a very low risk of complication. Generally, less than 24 hours of hospitalization is required and return to normal activities, including work, is almost immediate. Endometrial ablation is likely to become a mainstay of treatment for menorrhagia as the technology and training become more readily available. PMID:21229128

  18. Molecular Profiling of Endometrial Malignancies

    PubMed Central

    Samarnthai, Norasate; Hall, Kevin; Yeh, I-Tien

    2010-01-01

    Molecular profiling of endometrial neoplasms reveals genetic changes in endometrial carcinomas that support the dualistic model, in which type I carcinomas are estrogen-dependent, low grade lesions and type II carcinomas are nonestrogen dependent and high grade. The molecular changes in type I endometrial carcinomas include mutations in PTEN, PIK3CA, KRAS, and β-catenin, along with microsatellite instability, whereas type II endometrial carcinomas are characterized by genetic alterations in p53, HER2/neu, p16, and E-cadherin. For endometrial neoplasms with a malignant mesenchymal component, C-MYC mutations and loss of heterozygosity are frequently seen in carcinosarcomas, and a fusion gene, JAZF1/JJAZ1, is distinctive for endometrial stromal sarcoma. In addition, p53 mutations may play an important role in tumorigenesis of undifferentiated endometrial sarcoma. These molecular changes can help in the diagnosis of endometrial neoplasms, as well as form the basis of molecular targeted therapy. PMID:20368795

  19. Brivanib Alaninate in Treating Patients With Recurrent or Persistent Endometrial Cancer

    ClinicalTrials.gov

    2016-03-16

    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

  20. INCIDENCE OF ENDOMETRIAL HYPERPLASIA

    PubMed Central

    REED, Susan D.; NEWTON, Katherine M.; CLINTON, Walter L.; EPPLEIN, Meira; GARCIA, Rochelle; ALLISON, Kimberly; VOIGT, Lynda F.; Weiss, Noel S.

    2009-01-01

    Objective Estimate age-specific incidence of endometrial hyperplasia: simple, complex, and atypical, in order of increasing likelihood of progression to carcinoma. Study design Women ages 18–90 years with endometrial pathology specimens (1985–2003) at a large integrated health plan were identified using automated data. Incidence rates were obtained by dividing the number of cases by the estimated number of female health plan enrollees who retained a uterus. Results Endometrial hyperplasia peak incidence was: simple-142/100,000 woman-years, complex-213/100,000 woman-years, both in the early 50s; and atypical-56/100,000 woman-years in the early 60s. Age-adjusted incidence decreased over the study period, especially for atypical hyperplasia. Conclusions Endometrial hyperplasia incidence without and with atypia peaks in the early postmenopausal years and in the early 60s, respectively. Given that some cases of endometrial hyperplasia likely go undiagnosed, the figures provided should be viewed as minimum estimates of the true incidence. PMID:19393600

  1. 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.

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

    ClinicalTrials.gov

    2016-10-26

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

  3. Prediction of histological types of endometrial cancer by endometrial cytology.

    PubMed

    Okadome, Masao; Saito, Toshiaki; Nishiyama, Naoko; Ariyoshi, Kazuya; Shimamoto, Kumi; Shimada, Takako; Kodama, Keisuke; Imamura, Shogo; Nishiyama, Ken-ichi; Taguchi, Kenichi

    2014-07-01

    Few studies have examined the accuracy of preoperative endometrial cytology in diagnosing low- and high-risk histology in women with endometrial cancer (EC). This single-institutional retrospective study compared the accuracy of endometrial cytology and biopsy in preoperatively predicting low-risk and high-risk histology of EC. Between January 2006 and March 2013, 198 women with EC were examined by endometrial cytology, endometrial biopsy and hysterectomy specimen in National Kyushu Cancer Center. Among these women, 110 had endometrial cytology samples available to compare with endometrial biopsy, and were enrolled in our study (mean age ± standard deviation: 59.57 ± 10.32 years). Single-use plastic endometrial suction curettes were used in 12 of the 110 cases and thin metallic curettes for the rest. For type 2 EC, which includes grade 3 endometrioid adenocarcinoma and non-endometrioid histology, biopsy was 67.6% sensitive (25/37) and 84.9% specific (62/73); whereas cytology was 70.3% sensitive (26/37) and 91.8% specific (67/73). Cytology precisely diagnosed only one of 14 cases of serous carcinoma, but it diagnosed 11 of the 14 cases as type 2 EC, and its accuracy in distinguishing EC types was not inferior to endometrial biopsy (10/14). For EC, 9.1% (10/110) were unevaluable using biopsy, significantly more than the 0% (0/110) by cytology (P = 0.002). Although preoperative prediction of serous carcinoma was difficult, endometrial cytology had a higher evaluable rate for EC types. Endometrial cytology may complement endometrial biopsy in preoperative women with EC. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  4. Recent Advances in Endometrial Cancer

    PubMed Central

    Tran, Arthur-Quan; Gehrig, Paola

    2017-01-01

    Endometrial cancer is the most common gynecologic malignancy in the United States, with yearly rates continuing to increase. Most women present with early stage disease; however, advanced disease carries a grave prognosis. As a result, novel therapies are currently under investigation for the treatment of endometrial cancer. These advances include a better understanding of the genetic basis surrounding the development of endometrial cancer, novel surgical therapies, and new molecular targets for the treatment of this disease. This review explores the literature regarding these advancements in endometrial cancer. PMID:28184290

  5. 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.

  6. Endometrial carcinoma stage I.

    PubMed

    Baram, A; Ron, I; Kupferminc, M; Inbar, M

    1997-01-01

    Standard staging and therapeutic approach to endometrial cancer involves lymph node sampling (LNS) at the time of total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Lymphadenectomy prolongs time of surgery and increases the risk of morbidity; where other predictors are available, it may not contribute important supplementary information. 185/247 women with stage I endometrial carcinoma underwent the standard surgery while 62 underwent TAH+BSO. Recurrence and survival were monitored for a mean of 6.5 years and retrospectively reviewed: the rates for groups with and without known lymph node status were alike [13.5% (25/185) recurrence for the former and 12.9% (8/62) for the latter, and 5-year survival rates of 75.7% (140/185) for the former and 74.2 (46/62) for the latter]. Myometrial invasion and histological grade appeared to have been highly accurate predictors without lymph node information. Because information on histological grade is available early and is highly predictive, its use could be incorporated into a revised management algorithm for stage I endometrial cancer which would depend upon ensuring lymphadenectomy for women with low grade histopathology and omitting it for those with high grades on the grounds that no further information is necessary to act appropriately.

  7. Recurrence of endometrial polyps.

    PubMed

    Paradisi, Roberto; Rossi, Stefania; Scifo, Maria Cristina; Dall'O', Francesca; Battaglia, Cesare; Venturoli, Stefano

    2014-01-01

    To estimate the recurrence rate of patients with endometrial polyps and to evaluate whether the recurrence can be correlated with the histopathologic features of the polyp. Two hundred and eighty-two women with endometrial polyps in both pre- or postmenopausal period and suffering from abnormal uterine bleeding or not were treated by resectoscopic surgery in a tertiary university hospital and were subsequently followed to check for polyp recurrence. Polyp recurrence rate after hysteroscopic surgery and correlation between recurrence and main demographic, hysteroscopic and histopathologic characteristics were analyzed. During mean ± SD follow-up period of 26.3 ± 19.7 months, the overall recurrence rate was high (13.3%) and did not vary (p = NS) with age, parity, weight or other demographic characteristics of the patients or with the hysteroscopic appearance. On the contrary, the histopathologic features showed significant differences between patients with and without polyp recurrence. Recurrence rate was higher (p < 0.001) in women with histopathologically hyperplastic polyps without atypia and lower (p < 0.001) in women with benign polyps. The study shows that after resectoscopic polypectomy, the recurrence rate of endometrial polyps is high (13.3%). Moreover, the hyperplastic polyps without atypia recur more frequently than benign ones. © 2014 S. Karger AG, Basel.

  8. Endometrial haemostasis and menstruation.

    PubMed

    Davies, Joanna; Kadir, Rezan A

    2012-12-01

    Under normal physiological circumstances menstruation is a highly regulated, complex process that is under strict hormonal control. During normal menstruation, progesterone withdrawal initiates menstruation. The cessation of menstrual bleeding is achieved by endometrial haemostasis via platelet aggregation, fibrin deposition and thrombus formation. Local endocrine, immunological and haemostatic factors interact at a molecular level to control endometrial haemostasis. Tissue factor and thrombin play a key role locally in the cessation of menstrual bleeding through instigation of the coagulation factors. On the other hand, fibrinolysis prevents clot organisation within the uterine cavity while plasminogen activator inhibitors (PAI) and thrombin-activatable fibrinolysis inhibitors control plasminogen activators and plasmin activity. Abnormalities of uterine bleeding can result from imbalance of the haemostatic factors. The most common abnormality of uterine bleeding is heavy menstrual bleeding (HMB). Modern research has shown that an undiagnosed bleeding disorder, in particular von Willebrand disease (VWD) and platelet function disorders, can be an underlying cause of HMB. This has led to a change in the approach to the management of HMB. While full haemostatic assessment is not required for all women presenting with HMB, menstrual score and bleeding score can help to discriminate women who are more likely to have a bleeding disorder and benefit from laboratory haemostatic evaluation. Haemostatic agents (tranexamic acid and DDAVP) enhance systemic and endometrial haemostasis and are effective in reducing menstrual blood loss in women with or without bleeding disorders. Further research is required to enhance our understanding of the complex interactions of haemostatic factors in general, and specifically within the endometrium. This will lead to the development of more targeted interventions for the management of abnormal uterine bleeding in the future.

  9. c-Kit proto-oncogene expression in endometrial hyperplasia and endometrial cancer.

    PubMed

    Yilmaz, Ercan; Celik, Onder; Simsek, Yavuz; Turkcuoglu, Ilgin; Celik, Ebru; Gül, Mehmet; Hascalik, Seyma; Aydin, Nasuhi Engin; Aydin, Engin

    2012-07-01

    To evaluate the expression of c-kit (CD117) in endometrial hyperplasia and endometrial cancer. Expression of c-kit in 10 normal endometrium, 18 simple endometrial hyperplasia, 16 complex endometrial hyperplasia (10 cases with atypia and 6 cases without atypia), and 6 endometrial cancer were investigated by immunohistochemistry. c-Kit expression decreased as the lesion progressed to endometrial cancer. Immunostaining was mostly focal and weak in the normal endometrium and was mostly diffuse and strong in the simple and complex endometrial hyperplasia. Simple and complex hyperplastic endometrial tissues express diffuse cytoplasmic staining for c-kit and the expression decreases with the progression of the lesion.

  10. Endometrial Intraepithelial Neoplasia (EIN) in endometrial biopsy specimens categorized by the 1994 World Health Organization classification for endometrial hyperplasia.

    PubMed

    Li, Xiao-Chao; Song, Wen-Jing

    2013-01-01

    Our study is to determine the presence of endometrial intraepithelial neoplasia (EIN) in endometrial biopsy specimens classified by the 1994 World Health Organization (WHO) criteria for endometrial hyperplasia. Endometrial biopsy specimens that were stained with hematoxylin and eosin (HE) were examined and categorized by the WHO 1994 criteria and for the presence of EIN as defined by the International Endometrial Collaborative Group. β-catenin expression was examined by immunohistochemistry. A total of 474 cases of HE stained endometrial biopsy tissues were reviewed. There were 379 cases of simple endometrial hyperplasia, 16 with simple atypical endometrial hyperplasia, 48 with complex endometrial hyperplasia, and 31 with complex atypical endometrial hyperplasia. Among the 474 endometrial hyperplasia cases, there were 46 (9.7%) that were classified as EIN. Of these 46 cases, 11(2.9%) were classified as simple endometrial hyperplasia, 1 (6.3%) as simple atypical endometrial hyperplasia, 6 (12.5%) as complex endometrial hyperplasia, and 28 (90.3%) as complex atypical endometrial hyperplasia. EIN was associated with a higher rate of β-catenin positivity than endometrium classified as benign hyperplasia (72% vs. 22.5%, respectively, P < 0.001), but a lower rate than endometrial adenocarcinoma (72% vs. 96.2%, respectively, P < 0.001). In benign endometrial hyperplasia, high β-catenin expression was noted in the cell membranes, whereas in EIN and endometrial adenocarcinoma high expression was noted in the cytoplasm. In conclusion, EIN is more accurate than the WHO classification for the diagnosis of precancerous lesions of the endometrium.

  11. 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

  12. Risks of Endometrial Cancer Screening

    MedlinePlus

    ... Transvaginal ultrasound Endometrial sampling Tests are used to screen for different types of cancer. Some screening tests ... endometrium by inserting a brush, curette , or thin, flexible tube through the cervix and into the uterus. ...

  13. Drugs Approved for Endometrial Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for endometrial cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  14. Photodynamic therapy toward selective endometrial ablation

    NASA Astrophysics Data System (ADS)

    Tadir, Yona; Tromberg, Bruce J.; Krasieva, Tatiana B.; Berns, Michael W.

    1993-05-01

    Potential applications of photodynamic therapy for endometrial disease are discussed. Experimental models that may lead to diagnosis and treatment of endometriosis as well as selective endometrial ablation are summarized.

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

    ClinicalTrials.gov

    2014-10-09

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Cell Carcinoma; Endometrial Clear Cell Carcinoma; Endometrial Papillary Serous Carcinoma; Stage I Endometrial Carcinoma; Stage II Endometrial Carcinoma; Stage III Endometrial Carcinoma; Stage IV Endometrial Carcinoma

  16. Good practice with endometrial ablation.

    PubMed

    Garry, R

    1995-07-01

    To provide clear guidelines for the safe and effective performance of endometrial ablation. Representatives of American, Australian, British, and Canadian hysteroscopists were brought together to produce a consensus document of good practice in endometrial ablation. The guidelines were produced after researching the literature, combining the extensive experience of the group, and debating the relevant issues. Endometrial ablation is a new procedure. Correct patient selection is essential in producing good results. Patients must be counseled carefully about the advantages, disadvantages, and potential complications of this approach to the management of menstrual disorders. The main indication for endometrial ablation is heavy menstrual loss in the absence of organic disease. Excessive uterine size, the presence of active pelvic infection, and evidence of malignant and premalignant endometrium are absolute contraindications. Ablation can be produced by electrosurgical resection, rollerball or rollerbarrel ablation and Nd-YAG laser ablation. Severe complications can occur, and techniques should be adopted to avoid uterine perforation, hemorrhage, and excessive fluid absorption. In skilled hands, endometrial ablation can be a safe and effective treatment for menorrhagia.

  17. Clinical management of endometrial receptivity.

    PubMed

    Blesa, David; Ruiz-Alonso, María; Simón, Carlos

    2014-09-01

    The endometrial window of implantation (WOI), the cycle days during which normal embryo implantation can occur, has generally been assumed to begin on cycle day 19 or 20 of an idealized 28 days cycle and last for 4 to 5 days. Noyes et al took the first steps in defining the WOI by establishing a set of morphological criteria to evaluate endometrial development and receptivity, but recent studies have invalidated their use in the routine evaluation of infertility. Based on greater than 10 years of extensive research, our group has developed a molecular diagnostic tool (the endometrial receptivity array [ERA] test) based on the specific transcriptomic signature that identifies the receptive endometrium in natural and artificial (hormonal replacement therapy) cycles. The ERA test has shown that some patients have a delayed WOI, others have an advanced WOI, and others can have unusually short windows of receptivity. This identification and characterization of the WOI allows the personalization of the embryo transfer. In this review, we describe the ERA and our experience with its use in assessment of the endometrial receptivity in patients undergoing assisted reproduction.

  18. Endometrial polyps: when to resect?

    PubMed

    de Azevedo, Julia Marques da Rocha; de Azevedo, Ligia Marques da Rocha; Freitas, Fernando; Wender, Maria Celeste Osorio

    2016-03-01

    To determine the prevalence of malignant and premalignant endometrial polyps and to investigate the association of malignancy with specific factors. This is a retrospective study of women submitted to hysteroscopic resection of endometrial polyps between January 2005 and July 2013 at a university hospital in southern Brazil. Data regarding clinical characteristics and pathology findings were collected from patient charts. Of 359 patients, 87.2% had benign polyps and 9.9% had hyperplasia without atypia. Atypical hyperplasia was found in 2.6% of the sample. Endometrial adenocarcinoma was found in one woman (0.3%). A correlation was observed between malignant/premalignant polyps and patient age, menopausal status, and uterine bleeding. All patients with malignancies/premalignancies had abnormal uterine bleeding. Higher frequency of malignant polyps was observed in tamoxifen users, however, without statistical significance (p = 0.059%). Malignancy was not correlated with arterial hypertension, diabetes mellitus, obesity, hormone therapy, endometrial thickness, and polyp diameter. Malignant/premalignant findings had low prevalence and were absent in asymptomatic patients. From the data of this retrospective study, it is unclear whether routine polypectomy should be performed in asymptomatic patients. Further prospective studies including larger numbers of patients are required to guide treatment recommendations.

  19. Endometrial thickness predicts endometrial hyperplasia in patients with polycystic ovary syndrome.

    PubMed

    McCormick, Betsy A; Wilburn, Rochelle D; Thomas, Michael A; Williams, Daniel B; Maxwell, Rose; Aubuchon, Mira

    2011-06-30

    Body mass index is predictive of sonographic endometrial stripe thickness, which in turn is predictive of endometrial hyperplasia in patients with polycystic ovary syndrome. For every 1-mm increase in endometrial stripe, the odds ratio of hyperplasia increased by 1.48 (95% confidence interval, 1.04-2.10).

  20. Endometrial echo complex thickness in postmenopausal endometrial cancer.

    PubMed

    Chandavarkar, Uma; Kuperman, Julie M; Muderspach, Laila I; Opper, Neisha; Felix, Juan C; Roman, Lynda

    2013-10-01

    To determine the preoperative pelvic ultrasonographic characteristics of postmenopausal women diagnosed with endometrial cancer (EC) at our institution. Postmenopausal women with EC who underwent preoperative transvaginal pelvic ultrasound from 1999-2009 were identified from our institutional database. The histologic diagnosis was based on pathologic findings in the hysterectomy specimen. Endometrial echo complex (EEC) thickness was abstracted from ultrasound reports. In all instances, ultrasound preceded the biopsy by a maximum of 3 months. Means with standard deviations were calculated for all categorical data. Differences between type 1 and type 2 ECs were determined using Mann-Whitney U tests and Chi squared/Fisher's exact tests, as appropriate. A p-value of <0.05 was considered statistically significant. Among 250 patients with postmenopausal EC, 156 had type 1 EC while 94 had type 2 EC. Thirty-six percent of the cohort had an EEC ≤ 4 mm, including 37% of patients with type 1 EC and 34% of patients with type 2 EC (p=0.63). There were no significant differences between type 1 and type 2 ECs in any demographic characteristic, other than likelihood of postmenopausal bleeding. Current expert opinion recommends no further diagnostic procedure in a woman with postmenopausal bleeding and an EEC ≤ 4 mm. These results indicate that a sizable proportion of women with EC have EECs ≤ 4 mm during their initial evaluation. An EEC ≤ 4 mm does not completely rule out endometrial cancer and cannot supplant histologic evaluation. © 2013.

  1. Endometrial aspiration cytology in gynecological disorders

    PubMed Central

    Jadhav, Meenal V.; Phatke, Anjali S.; Kadgi, Nalini Vinayak; Rane, Sharda R.; Kulkarni, Kalpana K.

    2016-01-01

    Context: Endometrial aspiration is not a popular modality for the study of the endometrium despite its simplicity and potential utility. Aim: The present study was aimed at evaluating the utility of endometrial aspiration in various gynecological disorders. Materials and Methods: In this diagnostic accuracy study, 55 prospectively registered women with various gynecological disorders were evaluated clinically and subjected to endometrial aspiration cytology and study of endometrial histology. Endometrial aspiration was performed by infant feeding tube in 10 cases and intra cath cannula in 45 cases. The slides were stained with rapid Papanicolaou (PAP) stain and Leishman stain. Results: Endometrial aspiration cytology showed 90% and 94.6% sampling adequacy with infant feeding tube and intra cath cannula, respectively. Intra cath cannula was very convenient to handle and superior to infant feeding tube in aspirating the endometrium. Of the two stains used, rapid PAP stain was less time-consuming and superior to Leishman stain in studying the nuclear details. Leishman stain was helpful in detecting cytoplasmic vacuoles of secretory endometrium. Overall diagnostic accuracy of endometrial cytology was 90.4% while that for morphological hormonal evaluation was 97.6%. It enjoyed a sensitivity of 91.66%, a specificity of 88.23%, positive predictive value of 94.28%, and negative predictive value of 83.33%. Conclusion: Intra cath cannula emerged as an inexpensive, effective, and convenient device for endometrial aspiration. Endometrial aspiration proved to be a fairly effective, simple, and informative diagnostic modality. PMID:27011435

  2. Hypertriglyceridemia is Frequent in Endometrial Cancer Survivors

    PubMed Central

    Hirasawa, Akira; Makita, Kazuya; Akahane, Tomoko; Yokota, Megumi; Yamagami, Wataru; Banno, Kouji; Susumu, Nobuyuki; Aoki, Daisuke

    2013-01-01

    Objective Previous studies have reported an association between endometrial cancer and the risk of metabolic syndrome; however, the pattern of endometrial cancer-associated dyslipidemia is not well understood. The standard therapy for endometrial cancer is total abdominal hysterectomy and bilateral salpingo-oophorectomy. Premenopausal bilateral salpingo-oophorectomy may cause adverse events, including dyslipidemia. Gynecologists have to care dyslipidemia in endometrial cancer survivors at cancer follow-up clinic. Methods This study included 693 patients who had undergone bilateral salpingo-oophorectomy, and included 412 women with incident endometrial cancer and 281 controls. We divided the patients into two categories according to whether they had a premenopausal or postmenopausal bilateral oophorectomy. Serum lipid levels were measured and statistically analyzed. Results Hypertriglyceridemia was statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy both before and after menopause than in the corresponding non-endometrial cancer controls. High levels of low-density lipoprotein cholesterol and a high low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio were statistically more frequent in patients who had undergone bilateral salpingo-oophorectomy before menopause than in non-endometrial cancer controls. Conclusions Our report highlights the importance of the relationship between endometrial cancer and lipid metabolism, which may aid in preventing cerebrovascular or cardiovascular diseases due to dyslipidemia and improving the quality of life in endometrial cancer survivors. PMID:23999769

  3. A proposed model for endometrial serous carcinogenesis.

    PubMed

    Zheng, Wenxin; Xiang, Li; Fadare, Oluwole; Kong, Beihua

    2011-01-01

    Endometrial serous carcinomas constitute no more than 10% of endometrial adenocarcinomas, but frequently present at an advanced stage and have a significantly worse prognosis than the more common low-grade and intermediate-grade endometrioid adenocarcinomas. The neoplasm's potential for rapid tumor progression and the high mortality that is associated with advanced-stage disease underscore the importance of understanding endometrial serous carcinogenesis so that its precancers can be diagnosed and an effective therapeutic intervention can be administered. In this study, the authors summarize the current state of knowledge on endometrial serous carcinogenesis and propose a model for its development based on recent work from our group and published data from other researchers. In this model, endometrial serous carcinoma arises predominantly in the resting endometrium, manifesting first as p53 immunoreactive, morphologically normal endometrial cells (p53 signatures), evolving to endometrial glandular dysplasia (which is the first morphologically identifiable precursor lesion), then to serous endometrial intraepithelial carcinoma (a carcinoma with a noninvasive growth pattern in the uterus but which is not infrequently associated with extrauterine disease), and finally into fully developed serous carcinoma. Endometrial glandular dysplasia is a lesion, which can be diagnosed by routine microscopic evaluation, whose ablation or removal may potentially offer the opportunity to prevent the development of the associated malignancy. The diagnostic criteria, practical applicability, and evidentiary basis for the delineation of this lesion are studied.

  4. Mig-6 Mouse Model of Endometrial Cancer.

    PubMed

    Kim, Tae Hoon; Yoo, Jung-Yoon; Jeong, Jae-Wook

    2017-01-01

    Endometrial cancer is a frequently occurring gynecological disorder. Estrogen-dependent endometrioid carcinoma is the most common type of gynecological cancer. One of the major pathologic phenomena of endometrial cancer is the loss of estrogen (E2) and progesterone (P4) control over uterine epithelial cell proliferation. P4 antagonizes the growth-promoting properties of E2 in the uterus. P4 prevents the development of endometrial cancer associated with unopposed E2 by blocking E2 actions. Mitogen inducible gene 6 (Mig-6, Errfi1, RALT, or gene 33) is an immediate early response gene that can be induced by various mitogens and common chronic stress stimuli. Mig-6 has been identified as an important component of P4-mediated inhibition of E2 signaling in the uterus. Decreased expression of MIG-6 is observed in human endometrial carcinomas. Transgenic mice with Mig-6 ablation in the uterus develop endometrial hyperplasia and E2-dependent endometrial cancer. Thus, MIG-6 has a tumor suppressor function in endometrial tumorigenesis. The following discussion summarizes our current knowledge of Mig-6 mouse models and their role in understanding the molecular mechanisms of endometrial tumorigenesis and in the development of therapeutic approaches for endometrial cancer.

  5. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 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...

  6. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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...

  7. Endometrial Ablation: a Review Article.

    PubMed

    Famuyide, Abimbola

    2017-09-06

    The destruction of the endometrium in women with heavy menstrual bleeding has been employed for well over a century and the various techniques of delivering forms of thermal energy have been modified over the years to assure a safe and effective treatment approach. Today, six non-resectoscopic devices are approved for use in the United States in addition to resectoscopic techniques that rely on skillful use of the operative hysteroscope. Regardless of the technique employed, endometrial ablation uniformly reduces menstrual blood loss, improves general and menstrual related quality of life and prevents hysterectomy in four out of five women who undergo the procedure. When patients are appropriately selected, outcomes are optimized and risks of serious complications are minimized. This article reviews the literature with singular reference to non-resectoscopic endometrial ablation procedures including historical background, appropriate patient selection, clinical outcomes data, complication and special or unique considerations. Copyright © 2017. Published by Elsevier Inc.

  8. Expression of Endometrial Receptivity Genes Increase After Myomectomy of Intramural Leiomyomas not Distorting the Endometrial Cavity.

    PubMed

    Unlu, Cihat; Celik, Onder; Celik, Nilufer; Otlu, Baris

    2016-01-01

    This study was designed to investigate whether endometrial receptivity genes are altered in infertile patients with intramural leiomyomas (IM) not distorting the endometrial cavity undergoing myomectomy. We measured endometrial HOXA-10, HOXA-11, LIF, ITGB3, and ITGAV messenger RNA (mRNA) expressions levels before and after myomectomy/metroplasty during mid-luteal phase in participants with IM, submucosal leiomyomas (SM), and septate uterus and fertile participants without fibroids. Initial endometrial sampling was obtained at the time of surgery, and second sampling was obtained 3 months after myomectomy/metroplasty. Expressions of each gene were evaluated using real-time reverse transcriptase polymerase chain reaction (RT-PCR). A trend toward decreased endometrial HOXA-10, HOXA-11, and ITGAV mRNA expression was detected in both SM and IM groups before myomectomy when compared to both fertile group and septate uterus. However, the differences failed to show statistical significance. After myomectomy of IM, we have detected 12.8-fold increase in endometrial HOXA-10 mRNA expression and 9.0-fold increase in endometrial HOXA-11 mRNA expression. This increase in endometrial HOXA-10 and 11 mRNA expression was significant. Accordingly, 2 patients having intramural fibroids greater than 5 cm were able to remain pregnant after myomectomy. Conversely, submucosal myomectomy did not cause any significant effect on endometrial receptivity markers. Likewise, all markers of endometrial receptivity remained unchanged after metroplasty. Myomectomy of IM have favorable effect on endometrial HOXA-10 and 11 mRNA expression.

  9. 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

  10. Endometrial polyps in 2 African pygmy hedgehogs.

    PubMed

    Phillips, Irene D; Taylor, Jacqueline J; Allen, Andrew L

    2005-06-01

    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.

  11. Diagnosis and Management of Endometrial Cancer.

    PubMed

    Braun, Michael M; Overbeek-Wager, Erika A; Grumbo, Robert J

    2016-03-15

    Endometrial cancer is the most common gynecologic malignancy. It is the fourth most common cancer in women in the United States after breast, lung, and colorectal cancers. Risk factors are related to excessive unopposed exposure of the endometrium to estrogen, including unopposed estrogen therapy, early menarche, late menopause, tamoxifen therapy, nulliparity, infertility or failure to ovulate, and polycystic ovary syndrome. Additional risk factors are increasing age, obesity, hypertension, diabetes mellitus, and hereditary nonpolyposis colorectal cancer. The most common presentation for endometrial cancer is postmenopausal bleeding. The American Cancer Society recommends that all women older than 65 years be informed of the risks and symptoms of endometrial cancer and advised to seek evaluation if symptoms occur. There is no evidence to support endometrial cancer screening in asymptomatic women. Evaluation of a patient with suspected disease should include a pregnancy test in women of childbearing age, complete blood count, and prothrombin time and partial thromboplastin time if bleeding is heavy. Most guidelines recommend either transvaginal ultrasonography or endometrial biopsy as the initial study. The mainstay of treatment for endometrial cancer is total hysterectomy with bilateral salpingo-oophorectomy. Radiation and chemotherapy can also play a role in treatment. Low- to medium-risk endometrial hyperplasia can be treated with nonsurgical options. Survival is generally defined by the stage of the disease and histology, with most patients at stage I and II having a favorable prognosis. Controlling risk factors such as obesity, diabetes, and hypertension could play a role in the prevention of endometrial cancer.

  12. 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

  13. Sunitinib Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

    ClinicalTrials.gov

    2017-01-31

    Endometrial Adenocarcinoma; Endometrial Endometrioid Adenocarcinoma; Endometrial Serous Adenocarcinoma; Recurrent Uterine Corpus Carcinoma; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer; Uterine Carcinosarcoma; Uterine Corpus Carcinosarcoma

  14. Chemomertical analysis of endometrial tissue fluorescence spectra

    NASA Astrophysics Data System (ADS)

    Vaitkuviene, Aurelija; Auksorius, E.; Fuchs, D.; Gavriushin, V.

    2002-10-01

    An effort has been made to detect neopterin spectrum in fluorescence of premalignant endometrial tissue and to estimate the number of fluorophores naturally existing in the tissue with fluorescence present above the noise level. Endometrial Tissue fluorescence was measured in vitro by excitation with the third harmonic of Nd YAG laser. Multivariate curve resolution was used for testing neopterin presence in endometrial tissue. Fluorescence spectra ofneopterin was measured and used as a target spectrum for testing. Seven factors -fluorescence ofnatural fluorophores ofendometrial tissue were found to be present above the noise level in the overall autofluorescence. Neopterin concentration may be too low in endometrial tissue to make its fluorescence above the noise level because neopterin spectrum was not found to be among the spectra resolved by multivariate curve resolution. An intensity increase in the neopterin spectrum spectral region in hyperplastic endometrial samples might be associated with neopterin concentration increase.

  15. 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.

  16. The utility of endometrial thickness measurement in asymptomatic postmenopausal women with endometrial fluid.

    PubMed

    Seckin, B; Ozgu-Erdinc, A S; Dogan, M; Turker, M; Cicek, M N

    2016-01-01

    The aim of this study was to assess the clinical usefulness of sonographic endometrium thickness measurement in asymptomatic postmenopausal women with endometrial fluid collection. Fifty-two asymptomatic postmenopausal women with endometrial fluid, who underwent endometrial sampling were evaluated. Histopathological findings revealed that 25 (48.1%) women had insufficient tissue, 20 (38.4%) had atrophic endometrium and 7 (13.5%) had endometrial polyps. No case of malignancy was found. There was no statistically significant difference between the various histopathological categories (insufficient tissue, atrophic endometrium and polyp) with regard to the mean single-layer endometrial thickness (1.54 ± 0.87, 2.04 ± 1.76 and 1.79 ± 0.69 mm, respectively, p = 0.436). Out of 44 patients with endometrial thickness of less than 3 mm, 38 (86.4%) had atrophic changes or insufficient tissue and 6 (13.6%) had endometrial polyps. In conclusion, if the endometrial thickness is 3 mm or less, endometrial sampling is not necessary in asymptomatic postmenopausal women with endometrial fluid.

  17. From endometrial hyperplasia to endometrial cancer: insight into the biology and possible medical preventive measures.

    PubMed

    Boruban, Melih C; Altundag, Kadri; Kilic, Gokhan S; Blankstein, Josef

    2008-04-01

    Controversies are still seen in the histological differential diagnosis of hyperplasia and well-differentiated endometrial carcinoma. Prediction of endometrial cancer in patients with hyperplasia with atypia, with the available markers has not been reliable yet. Hence these patients require more attention in the clinical management. Endometrial hyperplasia is proliferation of endometrial glands resulting in a higher gland : stroma ratio. Cytological atypia, which may progress to or co-exist with endometrial cancer and other pathological changes, result from estrogen stimulation unopposed by progesterone. Biomarkers whose expression is altered in cases of endometrial hyperplasia or cancer such as progesterone receptor, insulin-like growth factor I, retinaldehyde dehydrogenase type II, and secreted frizzled-related protein 4, seem to be promising to use as early-stage tumor markers. Mutation of PTEN is present in 83% of endometrial adenocarcinoma cases, making it the most frequent early molecular genetic alteration in type 1 endometrial tumors, which are generally associated with hyperplasia. p53 gene mutation is not found in endometrial hyperplasia, but researchers have detected this mutation in 20% of cases of endometrial carcinoma and 90% of cases of serous endometrial tumors. Cyclooxygenase-2 is important in tumorogenic transformation of hyperplasia. Expression of cyclooxygenase-2 decreases apoptosis, increases angiogenesis, and is related to invasiveness. Cyclooxygenase-2 expression increases significantly in cases of well-differentiated endometrial adenocarcinoma. Prostaglandin E2 is known to regulate aromatase gene expression and is the product of cyclooxygenase-2. The data about aromatase inhibitors are promising; in breast cancer patients, treatment with tamoxifen induces uterine abnormalities as early as 3 months after the initiation of therapy. In contrast, these abnormalities are not seen in patients who receive aromatase inhibitors and switched therapy

  18. 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

  19. 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

  20. Cabozantinib-S-Malate in Treating Patients With Recurrent or Metastatic Endometrial Cancer

    ClinicalTrials.gov

    2017-03-20

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

  1. Endometrial receptivity array: Clinical application.

    PubMed

    Mahajan, Nalini

    2015-01-01

    Human implantation is a complex process requiring synchrony between a healthy embryo and a functionally competent or receptive endometrium. Diagnosis of endometrial receptivity (ER) has posed a challenge and so far most available tests have been subjective and lack accuracy and a predictive value. Microarray technology has allowed identification of the transcriptomic signature of the window of receptivity window of implantation (WOI). This technology has led to the development of a molecular diagnostic tool, the ER array (ERA) for diagnosis of ER. Use of this test in patients with recurrent implantation failure (RIF) has shown that the WOI is displaced in a quarter of these patients and use of a personalized embryo transfer (pET) on the day designated by ERA improves reproductive performance. Our results in the Indian population revealed an endometrial factor in 27.5% RIF patients, which was significantly greater than the non-RIF group 15% (P = 0.04). After pET, the overall ongoing pregnancy rate was 42.4% and implantation rate was 33%, which was at par with our in-vitro fertilization results over 1-year. We also performed ERA in patients with persistently thin endometrium, and it was reassuring to find that the endometrium in 75% of these patients was receptive despite being 6 mm or less. A pregnancy rate of 66.7% was achieved in this group. Though larger studies are required to validate these results ERA has become a useful tool in our diagnostic armamentarium for ER.

  2. Endometrial receptivity array: Clinical application

    PubMed Central

    Mahajan, Nalini

    2015-01-01

    Human implantation is a complex process requiring synchrony between a healthy embryo and a functionally competent or receptive endometrium. Diagnosis of endometrial receptivity (ER) has posed a challenge and so far most available tests have been subjective and lack accuracy and a predictive value. Microarray technology has allowed identification of the transcriptomic signature of the window of receptivity window of implantation (WOI). This technology has led to the development of a molecular diagnostic tool, the ER array (ERA) for diagnosis of ER. Use of this test in patients with recurrent implantation failure (RIF) has shown that the WOI is displaced in a quarter of these patients and use of a personalized embryo transfer (pET) on the day designated by ERA improves reproductive performance. Our results in the Indian population revealed an endometrial factor in 27.5% RIF patients, which was significantly greater than the non-RIF group 15% (P = 0.04). After pET, the overall ongoing pregnancy rate was 42.4% and implantation rate was 33%, which was at par with our in-vitro fertilization results over 1-year. We also performed ERA in patients with persistently thin endometrium, and it was reassuring to find that the endometrium in 75% of these patients was receptive despite being 6 mm or less. A pregnancy rate of 66.7% was achieved in this group. Though larger studies are required to validate these results ERA has become a useful tool in our diagnostic armamentarium for ER. PMID:26538853

  3. Isolated Abdominal Wall Metastasis of Endometrial Carcinoma

    PubMed Central

    Simões, Jorge; Gonçalves, Matilde; Matos, Isabel

    2014-01-01

    A woman in her mid-60s presented with a bulky mass on the anterior abdominal wall. She had a previous incidental diagnosis of endometrial adenocarcinoma FIGO stage IB following a vaginal hysterectomy. Physical exam and imaging revealed a well circumscribed bulging tumour at the umbilical region, measuring 10 × 9 × 9 cm, with overlying intact skin and subcutaneous tissue. Surgical resection was undertaken, and histological examination showed features of endometrial carcinoma. She began chemotherapy and is alive with no signs of recurrent disease one year after surgery. This case brings up to light an atypical location of a solitary metastasis of endometrial carcinoma. PMID:25349753

  4. Prevalence of Co-existing Endometrial Carcinoma in Patients with Preoperative Diagnosis of Endometrial Hyperplasia

    PubMed Central

    Kadirogullari, Pinar; Atalay, Cemal Resat; Sari, Mustafa Erkan

    2015-01-01

    Introduction Endometrial hyperplasia has been associated with the presence of concomitant endometrial carcinoma. In this study, patients who were diagnosed with endometrial hyperplasia and had hysterectomy, determination of the incidence of endometrial cancer accompanying postoperatively and clinical parameters associated with cancer are aimed. Materials and Methods Endometrial biopsies were taken from patients for various reasons and among them 158 patients diagnosed with endometrial hyperplasia from pathologic examination results were retrospectively evaluated. All of the patient’s age, parity, weight, transvaginal ultrasound measured by endometrial thickness, concomitant systemic disease (diabetes, hypertension, hypothyroidism), tamoxifen use, hormone use and whether in reproductive age or menopause were all questioned. Patients who applied with endometrial cancer, their cervical stromal involvement, lymph node involvement, cytology positivity and omental metastases were examined. Patients were classified according to their stage and grade. Patients who had intraoperative frozen were re-evaluated. Results Fifteen cases with preoperative endometrial hyperplasia diagnosed with endometrial cancer postoperatively, 2 cases had complex hyperplasia without atypia and 13 cases had complex atypical hyperplasia. The rate of preoperative hyperplasia with postoperative endometrial cancer was found to be 10.8% where by 15 cases of patients diagnosed with endometrial cancer postoperatively 11 cases were in postmenopausal period. In patients diagnosed with endometrial cancer according to their histologic types 14 cases had endometrioid adenocarcinoma while one patient with preoperative complex hyperplasia without atypia was diagnosed with serous papillary carcinoma postoperatively. Evaluation of stages in patients diagnosed with cancer, 7 cases of patients had stage IA, 7 cases of patients had stage IB, and 7 cases cases of patients with serous papillary carcinoma were

  5. Breast cancer susceptibility polymorphisms and endometrial cancer risk: a Collaborative Endometrial Cancer Study.

    PubMed

    Healey, Catherine S; Ahmed, Shahana; O'Mara, Tracy A; Ferguson, Kaltin; Lambrechts, Diether; Garcia-Dios, Diego A; Vergote, Ignace; Amant, Frederic; Howarth, Kimberley; Gorman, Maggie; Hodgson, Shirley; Tomlinson, Ian; Yang, Hannah P; Lissowska, Jolanta; Brinton, Louise A; Chanock, Stephen; Garcia-Closas, Montserrat; Hall, Per; Liu, Jianjun; Shah, Mitul; Pharoah, Paul D P; Thompson, Deborah J; Rebbeck, Timothy R; Strom, Brian L; Dunning, Alison M; Easton, Douglas F; Spurdle, Amanda B

    2011-12-01

    Recent large--scale association studies, both of genome-wide and candidate gene design, have revealed several single-nucleotide polymorphisms (SNPs) which are significantly associated with risk of developing breast cancer. As both breast and endometrial cancers are considered to be hormonally driven and share multiple risk factors, we investigated whether breast cancer risk alleles are also associated with endometrial cancer risk. We genotyped nine breast cancer risk SNPs in up to 4188 endometrial cases and 11,928 controls, from between three and seven Caucasian populations. None of the tested SNPs showed significant evidence of association with risk of endometrial cancer.

  6. Breast cancer susceptibility polymorphisms and endometrial cancer risk: a Collaborative Endometrial Cancer Study

    PubMed Central

    Ahmed, Shahana; O’Mara, Tracy A.; Ferguson, Kaltin; Lambrechts, Diether; Garcia-Dios, Diego A.; Vergote, Ignace; Amant, Frederic; Howarth, Kimberley; Gorman, Maggie; Hodgson, Shirley; Tomlinson, Ian; Yang, Hannah P.; Lissowska, Jolanta; Brinton, Louise A.; Chanock, Stephen; Garcia-Closas, Montserrat; Hall, Per; Liu, Jianjun; Shah, Mitul; Pharoah, Paul D.P.; Thompson, Deborah J.; Rebbeck, Timothy R.; Strom, Brian L.; Dunning, Alison M.; Easton, Douglas F.; Spurdle, Amanda B.

    2011-01-01

    Recent large--scale association studies, both of genome-wide and candidate gene design, have revealed several single-nucleotide polymorphisms (SNPs) which are significantly associated with risk of developing breast cancer. As both breast and endometrial cancers are considered to be hormonally driven and share multiple risk factors, we investigated whether breast cancer risk alleles are also associated with endometrial cancer risk. We genotyped nine breast cancer risk SNPs in up to 4188 endometrial cases and 11 928 controls, from between three and seven Caucasian populations. None of the tested SNPs showed significant evidence of association with risk of endometrial cancer. PMID:21965274

  7. Intraperitoneal Paclitaxel, Doxorubicin Hydrochloride, and Cisplatin in Treating Patients With Stage III-IV Endometrial Cancer

    ClinicalTrials.gov

    2017-08-23

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

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

    ClinicalTrials.gov

    2015-12-22

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Mucinous Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; Endometrioid 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; Uterine Carcinosarcoma

  9. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... with negative pressure. This device is used to study endometrial cytology (cells). (b) Classification... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction, and...

  10. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... with negative pressure. This device is used to study endometrial cytology (cells). (b) Classification... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction, and...

  11. 21 CFR 884.1185 - Endometrial washer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... with negative pressure. This device is used to study endometrial cytology (cells). (b) Classification... a recent cesarean section, and (iii) Warning: Do not attach to a wall or any external suction, and...

  12. The epidemic of endometrial cancer: a commentary.

    PubMed Central

    Jick, H; Walker, A M; Rothman, K J

    1980-01-01

    Vital statistics show that a rise in incidence of endometrial cancer began in the mid-1960s on the West Coast of the United States. This rise was continuous and reached a peak in 1975. Elsewhere, incidence rates for endometrial cancer rose during the 1970s. It now seems evident that much of the rise in all areas of the country was due to replacement estrogen treatment. We estimated from data obtained from the Commission on Professional and Hospital Activities-Professional Activity Study of Ann Arbor, Michigan, that over 15,000 cases of endometrial cancer were caused by replacement estrogens during the five-year period 1971--1975 alone. This represents one of the largest epidemics of serious iatrogenic disease that has ever occurred in this country. With the substantial fall in estrogen sales starting in January 1976, there has been an associated decline in the incidence rates of endometrial cancer nationwide. PMID:7356090

  13. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... endometrial cytology (cells). (b) Classification. Class II. The special controls for this device are: (1) FDA...) Indication: Only to evaluate the endometrium, and (ii) Contraindications: Pregnancy, history of uterine...

  14. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... endometrial cytology (cells). (b) Classification. Class II. The special controls for this device are: (1) FDA...) Indication: Only to evaluate the endometrium, and (ii) Contraindications: Pregnancy, history of uterine...

  15. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... endometrial cytology (cells). (b) Classification. Class II. The special controls for this device are: (1) FDA...) Indication: Only to evaluate the endometrium, and (ii) Contraindications: Pregnancy, history of uterine...

  16. 21 CFR 884.1100 - Endometrial brush.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... endometrial cytology (cells). (b) Classification. Class II. The special controls for this device are: (1) FDA...) Indication: Only to evaluate the endometrium, and (ii) Contraindications: Pregnancy, history of uterine...

  17. 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) Classification. Class II. The special controls for this device are: (1) FDA's: (i) “Use of International...

  18. 21 CFR 884.1060 - Endometrial aspirator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and pipette, or catheter. This device is used to study endometrial cytology (cells). (b) Classification. Class II. The special controls for this device are: (1) FDA's: (i) “Use of International...

  19. Revised FIGO staging system for endometrial cancer.

    PubMed

    Lewin, Sharyn N

    2011-06-01

    In 1988 the International Federation of Gynecologists and Obstetricians (FIGO) developed a surgical staging system for endometrial cancer. The FIGO staging system was recently revised in 2009 to reflect our growing understanding of the natural history of endometrial cancer. In this review, we describe the revised 2009 FIGO staging system for tumors of the uterine corpus and examine the effect of the new changes in the staging criteria.

  20. [Endometrial vasculature in women with hydrosalpinx].

    PubMed

    Kirichenko, A K; Khorzhevskiĭ, V A

    2014-01-01

    To study the endometrial vasculature in women with hydrosalpinx and to determine a possible correlation between its state and the morphometric parameters of other structural components of the uterine mucosa. The endometrium was studied in 20 patients with primary tubal infertility in hydrosalpinx. A control group included 20 women with established fertility and a regular menstrual cycle with a good obstetric and gynecological history. The spectrum of morphometric parameters included the relative volumes occupied by the endometrial glands and glandular epithelium; the height of the integumentary epithelium; and the number of stromal cells per mm2. Stereometric (glandular-stromal, epithelial-stromal) indices and epithelium/glandular lumen ratio were calculated. The endometrial vasculature was estimated by immunohistochemical assay of CD31- and CD34-expressing cells. There was a decrease in the specific volume occupied by positively stained vascular endotheliocytes and a predominance of the stromal component of the endometrium over its epithelial one. Correlations were found between the degree of development of the endometrial vasculature and endometrial glands, which reflects their normal relationships in the proliferation phase. In the study group, the correlation between the height of the integumentary epithelium and the development of the endometrial vasculature was moderately positive, which was absent in the control group where this correlation was strong and positive. The findings are evidence in favor of the negative impact of hydrosalpinx on the uterine mucosa. The found changes in the main endometrial structural components (vessels, glands, and stromal cells) reflect impaired mucosal maturation processes during the proliferation phase. The substantial negative impact of hydrosalpinx has an effect on the height of the integumentary epithelium of the endometrium. The given data suggest that there are significant and complex endometrial changes in hydrosalpinx

  1. Circulating Adiponectin and Risk of Endometrial Cancer

    PubMed Central

    Zheng, Qiaoli; Wu, Haijian; Cao, Jiang

    2015-01-01

    Background Adiponectin is an insulin-sensitizing hormone produced by adipocytes. It has been suggested to be involved in endometrial tumorigenesis. Published data have shown inconsistent results for the association between circulating adiponectin levels and endometrial cancer. In this study, we conducted a meta-analysis to evaluate the predictive value of circulating adiponectin levels on the development of endometrial cancer. Methods PubMed, Embase, ISI web of knowledge, and Cochrane databases were searched for all eligible studies, and the summary relative risk (SRR) was calculated. Additionally, we performed dose-response analysis with eight eligible studies. Results A total of 1,955 cases and 3,458 controls from 12 studies were included. The SRR for the ‘highest’ vs ‘lowest’ adiponectin levels indicated high adiponectin level reduced the risk of endometrial cancer [SRR = 0.40, 95% confidence interval (CI), 0.33–0.66]. Results from the subgroup analyses were consistent with the overall analysis. The SRR for each 1 µg/ml increase of adiponectin indicated a 3% reduction in endometrial cancer risk (95% CI: 2%–4%), and a 14% reduction for each increase of 5 µg/ml (95% CI: 9%–19%). No evidence of publication bias was found. Conclusions This meta-analysis demonstrates that low level of circulating adiponectin is a risk factor for endometrial cancer. PMID:26030130

  2. Pregnancy history and risk of endometrial cancer.

    PubMed

    Pocobelli, Gaia; Doherty, Jennifer A; Voigt, Lynda F; Beresford, Shirley A; Hill, Deirdre A; Chen, Chu; Rossing, Mary Anne; Holmes, Rebecca S; Noor, Zorawar S; Weiss, Noel S

    2011-09-01

    Epidemiologic studies are consistent in finding that women who have had at least one birth are less likely to develop endometrial cancer. Less clear is whether timing of pregnancies during reproductive life influences risk, and the degree to which incomplete pregnancies are associated with a reduced risk. We evaluated pregnancy history in relation to endometrial cancer risk using data from a series of 4 population-based endometrial cancer case-control studies of women 45-74 years of age (1712 cases and 2134 controls) during 1985-2005 in western Washington State. Pregnancy history and information on other potential risk factors were collected by in-person interviews. Older age at first birth was associated with a reduced risk of endometrial cancer after adjustment for number of births and age at last birth (test for trend P = 0.004). The odds ratio comparing women at least 35 years of age at their first birth with those younger than 20 years was 0.34 (95% confidence interval = 0.14-0.84). Age at last birth was not associated with risk after adjustment for number of births and age at first birth (test for trend P = 0.830). Overall, a history of incomplete pregnancies was not associated with endometrial cancer risk to any appreciable degree. In this study, older age at first birth was more strongly associated with endometrial cancer risk than was older age at last birth. To date, there remains some uncertainty in the literature on this issue.

  3. Molecular Pathogenesis of Endometrial and Ovarian Cancer

    PubMed Central

    Merritt, Melissa A.; Cramer, Daniel W.

    2013-01-01

    Pregnancy, breastfeeding, and oral contraceptive pill use interrupt menstrual cycles and reduce endometrial and ovarian cancer risk. This suggests the importance of turnover within Mullerian tissues, where the accumulation of mutations in p53 and PTEN has been correlated with number of cycles. The most common type of endometrial cancer (Type I) is endometrioid and molecular abnormalities include mutations in PTEN, KRAS and β-catenin. The Type I precursor is Endometrial lntraepithelial Neoplasia which displays PTEN defects. Type II endometrial cancer (whose precursors are less clear) includes serous and clear cell tumors and the most common alteration is p53 mutation. For ovarian cancer, histopathologic types parallel endometrial cancer and include serous, mucinous, endometrioid, and clear cell; some molecular features are also shared. The most frequent type of ovarian cancer is high grade serous that often displays p53 mutation and its precursor lesions may originate from normal-appearing fallopian tube epithelium that contains a p53 “signature”. Mutations in KRAS, BRAF and PTEN are described in mucinous, endometrioid and low grade serous cancers and these may originate from ovarian cortical inclusion cysts. A consideration of molecular and other pathogenetic features, like epidemiology and histopathology, may provide a bener understanding of endometrial and ovarian cancer. PMID:22112481

  4. Controversies in the Management of Endometrial Carcinoma

    PubMed Central

    Zhang, Ying; Wang, Jian

    2010-01-01

    Endometrial carcinoma is the most common type of female genital tract malignancy. Although endometrial carcinoma is a low grade curable malignancy, the condition of the disease can range from excellent prognosis with high curability to aggressive disease with poor outcome. During the last 10 years many researches have provided some new valuable data of optimal treatments for endometrial carcinoma. Progression in diagnostic imaging, radiation delivery systems, and systemic therapies potentially can improve outcomes while minimizing morbidity. Firstly, total hysterectomy and bilateral salphingo-oophorectomy is the primary operative procedure. Pelvic lymhadenectomy is performed in most centers on therapeutic and prognostic grounds and to individualize adjuvant treatment. Women with endometrial carcinoma can be readily segregated intraoperatively into “low-risk” and “high-risk” groups to better identify those women who will most likely benefit from thorough lymphadenectomy. Secondly, adjuvant therapies have been proposed for women with endometrial carcinoma postoperatively. Postoperative irradiation is used to reduce pelvic and vaginal recurrences in high risk cases. Chemotherapy is emerging as an important treatment modality in advanced endometrial carcinoma. Meanwhile the availability of new hormonal and biological agents presents new opportunities for therapy. PMID:20613958

  5. Laparoscopic pelvic surgery for endometrial cancer.

    PubMed

    Tay, Eng-Hseon

    2009-02-01

    The traditional approach for the treatment of endometrial cancer by laparotomy is increasingly being replaced by laparoscopic surgery. The advantages of laparoscopy have been well-documented. Laparoscopy avoids the morbidity of a laparotomy, overcomes the limitations of vaginal hysterectomy, provides adequate pathological information for an accurate surgical staging and expedites the postoperative recovery of patients. This paper reports the outcome of a series of 50 consecutive cases of laparoscopic hysterectomy and pelvic lymphadenectomy for endometrial cancers that were performed by the author. The objective is to review the perioperative, postoperative experience and survival outcomes of patients with endometrial cancer managed by laparoscopic surgery performed by a single surgeon. The records of 50 consecutive patients with endometrial cancers from October 1995 to October 2007 treated by laparoscopic pelvic lymphadenectomy and laparoscopic hysterectomy (total and assisted) were retrospectively reviewed. Data on patients' attributes, endometrial cancers, surgical procedures, surgical complications and morbidity, perioperative experience, length of hospital stays and clinical outcome were analysed. Laparoscopic surgery was successful in all 50 patients and is clearly an option for the treatment of early endometrial cancer. Careful patient selection and surgical competency are instrumental in ensuring successful treatment.

  6. Does a p53 "Wild-type" Immunophenotype Exclude a Diagnosis of Endometrial Serous Carcinoma?

    PubMed

    Fadare, Oluwole; Roma, Andres A; Parkash, Vinita; Zheng, Wenxin; Walavalkar, Vighnesh

    2017-09-22

    An aberrant p53 immunophenotype may be identified in several histotypes of endometrial carcinoma, and is accordingly recognized to lack diagnostic specificity in and of itself. However, based on the high frequency with which p53 aberrations have historically been identified in endometrial serous carcinoma, a mutation-type immunophenotype is considered to be highly sensitive for the histotype. Using an illustrative case study and a review of the literature, we explore a relatively routine diagnostic question: whether the negative predictive value of a wild-type p53 immunophenotype for serous carcinoma is absolute, that is, whether a p53-wild type immunophenotype is absolutely incompatible with a diagnosis of serous carcinoma. The case is an advanced stage endometrial carcinoma that was reproducibly classified by pathologists from 3 institutions as serous carcinoma based on its morphologic features. By immunohistochemistry, the tumor was p53-wild type (DO-7 clone), diffusely positive for p16 (block positivity), and showed retained expression of PTEN, MSH2, MSH6, MLH1, and PMS2. Next generation sequencing showed that there indeed was an underlying mutation in TP53 (D393fs*78, R213*). The tumor was microsatellite stable, had a low mutational burden (4 mutations per MB), and displayed no mutations in the exonuclease domain of DNA polymerase epsilon (POLE) gene. Other genomic alterations included RB1 mutation (R46fs*19), amplifications in MYST3 and CRKL, and ARID1A deletion (splice site 5125-94_5138del108). A review of the recent literature identified 5 studies in which a total of 259 cases of serous carcinoma were whole-exome sequenced. The average TP53 mutational rate in endometrial serous carcinoma was only 75% (range, 60 to 88). A total of 12 (33%) of 36 immunohistochemical studies reported a p53-aberrant rate of <80% in endometrial serous carcinoma. We discuss in detail several potential explanations that may underlie the scenario of serous carcinoma-like morphology

  7. 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

  8. 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.

  9. Sleep duration and endometrial cancer risk.

    PubMed

    Sturgeon, Susan R; Luisi, Nicole; Balasubramanian, Raji; Reeves, Katherine W

    2012-04-01

    Recent data indicate that night shift work is associated with increased endometrial cancer risk, perhaps through a pathway involving lower melatonin production. Melatonin is an antiestrogenic hormone, with production in a circadian pattern that is dependent on presence of dark at night. Sleep duration is positively associated with melatonin production and may be an indicator of melatonin levels in epidemiologic studies. We evaluated associations between self-reported sleep duration and endometrial cancer risk using publicly available prospective data on 48,725 participants in the Women's Health Initiative Observational Study, among whom 452 adjudicated incident cases of endometrial cancer were diagnosed over approximately 7.5 years of follow-up. Sleep duration was self-reported at baseline. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for endometrial cancer risk with adjustment for potential confounders. Most women reported sleeping ≤ 6 (33.3%) or 7 (38.5%) h each night; fewer reported sleeping 8 (23.4%) or ≥ 9 (4.8%) h each night. In adjusted analyses, there was an indication of reduced risk associated with longer sleep duration, though no statistically significant association was observed. Women who slept ≥ 9 h had a nonsignificant reduced risk of endometrial cancer compared with women who slept ≤ 6 h (HR = 0.87; 95% CI = 0.51-1.46). We found weak evidence of an association between sleep duration and endometrial cancer risk. Self-reported sleep duration may not adequately represent melatonin levels, thus further studies utilizing urinary melatonin levels are necessary to establish the mechanism by which night shift work increases endometrial cancer risk.

  10. MORPHOLOGICAL PATTERN OF ENDOMETRIAL BIOPSIES IN SOUTHWESTERN NIGERIA.

    PubMed

    Abdullahi, Y M; Ajani, M A; Iyapo, O; Aramide, K O; Okolo, C A; Akang, Eeu

    2016-12-01

    Endometrium remains the most sensitive indicator of ovarian function and endometrial biopsy is one of the diagnostic procedures in endometrial pathology. The current study was carried out to examine the morphological pattern of endometrial biopsies in Ibadan, South-western Nigeria and compare the results with similar studies. A retrospective study was undertaken to review all cases of endometrial biopsies received in the Department of Pathology, University College Hospital, Ibadan between January 1999 and December 2008. The patients' data were retrieved from the surgical pathology daybooks and Histology Request forms. The neoplastic lesions were classified according to 2003 World Health Organization classification for endometrial neoplasms. A total of 2,444 cases of endometrial biopsies were received during the 10-year study period. The functional endometrial changes were the most common histopathological diagnostic category, accounting for 53.8% (1035) of cases. Other pathological diagnoses included endometritis (7.8%), simple endometrial hyperplasia (5.8%), partial hydatidiform mole (2.3%), complete hydatidiform mole (2.1%) and malignant neoplastic lesions (3.9%). Infertility was the most common (57%) indication for endometrial biopsies followed by uterine bleeding (33%) while the least common clinical indication were the menstrual disorders (10%). The functional endometrial changes account for the highest morphological patterns while malignant lesions account for the least pattern of the endometrial biopsies evaluated for etiological basis of infertility, uterine bleeding and menstrual disorders in Ibadan. Infertility was the commonest indication for endometrial biopsies while the least common clinical indication was menstrual disorders.

  11. Expression of leptin receptor in endometrial biopsies of endometrial and ovarian cancer patients

    PubMed Central

    MÉNDEZ-LÓPEZ, LUIS FERNANDO; DÁVILA-RODRÍGUEZ, MARTHA IMELDA; ZAVALA-POMPA, ANGEL; TORRES-LÓPEZ, ERNESTO; GONZÁLEZ-MARTÍNEZ, BLANCA EDELIA; LÓPEZ-CABANILLAS-LOMELÍ, MANUEL

    2013-01-01

    The adipokine leptin plays a critical role in the regulation of reproductive function and there has been growing interest in its potential role in the development of cancers in which obesity is an established risk factor. Serum leptin levels were found to be higher in patients diagnosed with endometrial and ovarian cancer compared to those observed in healthy individuals. This study was conducted to determine the expression of the leptin receptor (Ob-R) in endometrial biopsies of patients diagnosed with endometrial and ovarian cancer. In this preliminary study, immunohistochemistry (IHC) and the color deconvolution method were used to assess the expression levels of the Ob-R protein in three groups of endometrial tissue: one from patients diagnosed with endometrioid endometrial carcinoma, one from patients diagnosed with ovarian cancer and one from individuals without any diagnosed gynecologic disease (control group). Our results demonstrated that the highest expression of Ob-R protein in endometrial biopsies was detected in the ovarian cancer group (P=0.000). This finding suggests that changes in Ob-R expression may be assessed through the measurement of the optical density of endometrial biopsies and may become a useful tool in preventive screening, particularly for ovarian cancer. PMID:24649005

  12. Progestin Intrauterine Devices and Metformin: Endometrial Hyperplasia and Early Stage Endometrial Cancer Medical Management.

    PubMed

    Nwanodi, Oroma

    2017-07-08

    Globally, endometrial cancer is the sixth leading cause of female cancer-related deaths. Non-atypical endometrial hyperplasia (EH), has a lifetime progression rate to endometrial cancer ranging from less than 5%, if simple without atypia, to 40%, if complex with atypia. Site specific, long-acting intrauterine devices (IUDs) provide fertility sparing, progestin-based EH medical management. It is unclear which IUD is most beneficial, or if progesterone sensitizing metformin offers improved outcomes. For resolution, PubMed searches for "Mirena" or "Metformin," "treatment," "endometrial hyperplasia," or "stage 1 endometrial cancer," were performed, yielding 33 articles. Of these, 19 articles were included. The 60 mg high-dose frameless IUD/20 mcg levonorgestrel has achieved sustained regression of Grade 3 endometrial intraepithelial neoplasia for 14 years. Case series on early stage endometrial cancer (EC) treatment with IUDs have 75% or greater regression rates. For simple through complex EH with atypia, the 52 mg-IUD/10-20 mcg-LNG-14t has achieved 100% complete regression in 6-months. Clearly, IUDs have an outcome advantage over oral progestins. However, studies on metformin for EH, and of progestins or metformin for early stage EC management are underpowered, with inadequate dose ranges to achieve significant differences in, or optimal outcomes for, the treatment modalities. Therefore, outcomes from the feMMe trial for the 52 mg-IUD/10-20 mcg-LNG-14t and metformin will fill a gap in the literature.

  13. Fenretinide: A Novel Treatment for Endometrial Cancer

    PubMed Central

    Mittal, Navdha; Malpani, Saurabh; Dyson, Matthew; Ono, Masanori; Coon, John S.; Kim, Julie J.; Schink, Julian C.; Bulun, Serdar E.; Pavone, Mary Ellen

    2014-01-01

    Resistance to progestin treatment is a major hurdle in the treatment of advanced and reoccurring endometrial cancer. Fenretinide is a synthetic retinoid that has been evaluated in clinical trials as a cancer therapeutic and chemo-preventive agent. Fenretinide has been established to be cytotoxic to many kinds of cancer cells. In the present study, we demonstrate that fenretinide decreased cell viability and induced apoptosis in Ishikawa cells, which are an endometrial cancer cell line, in dose dependent manner in-vitro. This effect was found to be independent of retinoic acid nuclear receptor signaling pathway. Further, we have shown that this induction of apoptosis by fenretinide may be caused by increased retinol uptake via STRA6. Silencing of STRA6 was shown to decrease apoptosis which was inhibited by knockdown of STRA6 expression in Ishikawa cells. Results of an in-vivo study demonstrated that intraperitoneal injections of fenretinide in endometrial cancer tumors (created using Ishikawa cells) in mice inhibited tumor growth effectively. Immunohistochemistry of mice tumors showed a decrease in Ki67 expression and an increase in cleaved caspase-3 staining after fenretinide treatment when compared to vehicle treated mice. Collectively, our results are the first to establish the efficacy of fenretinide as an antitumor agent for endometrial cancer both in-vitro and in-vivo, providing a valuable rationale for initiating more preclinical studies and clinical trials using fenretinide for the treatment of endometrial cancer. PMID:25340777

  14. Fenretinide: a novel treatment for endometrial cancer.

    PubMed

    Mittal, Navdha; Malpani, Saurabh; Dyson, Matthew; Ono, Masanori; Coon, John S; Kim, Julie J; Schink, Julian C; Bulun, Serdar E; Pavone, Mary Ellen

    2014-01-01

    Resistance to progestin treatment is a major hurdle in the treatment of advanced and reoccurring endometrial cancer. Fenretinide is a synthetic retinoid that has been evaluated in clinical trials as a cancer therapeutic and chemo-preventive agent. Fenretinide has been established to be cytotoxic to many kinds of cancer cells. In the present study, we demonstrate that fenretinide decreased cell viability and induced apoptosis in Ishikawa cells, which are an endometrial cancer cell line, in dose dependent manner in-vitro. This effect was found to be independent of retinoic acid nuclear receptor signaling pathway. Further, we have shown that this induction of apoptosis by fenretinide may be caused by increased retinol uptake via STRA6. Silencing of STRA6 was shown to decrease apoptosis which was inhibited by knockdown of STRA6 expression in Ishikawa cells. Results of an in-vivo study demonstrated that intraperitoneal injections of fenretinide in endometrial cancer tumors (created using Ishikawa cells) in mice inhibited tumor growth effectively. Immunohistochemistry of mice tumors showed a decrease in Ki67 expression and an increase in cleaved caspase-3 staining after fenretinide treatment when compared to vehicle treated mice. Collectively, our results are the first to establish the efficacy of fenretinide as an antitumor agent for endometrial cancer both in-vitro and in-vivo, providing a valuable rationale for initiating more preclinical studies and clinical trials using fenretinide for the treatment of endometrial cancer.

  15. A unique spectrum of somatic PIK3CA (p110alpha) mutations within primary endometrial carcinomas.

    PubMed

    Rudd, Meghan L; Price, Jessica C; Fogoros, Sarah; Godwin, Andrew K; Sgroi, Dennis C; Merino, Maria J; Bell, Daphne W

    2011-03-15

    The goal of this study was to comprehensively define the incidence of mutations in all exons of PIK3CA in both endometrioid endometrial cancer (EEC) and nonendometrioid endometrial cancer (NEEC). We resequenced all coding exons of PIK3CA and PTEN, and exons 1 and 2 of KRAS, from 108 primary endometrial tumors. Somatic mutations were confirmed by sequencing matched normal DNAs. The biochemical properties of a subset of novel PIK3CA mutations were determined by exogenously expressing wild type and mutant constructs in U2OS cells and measuring levels of AKT(Ser473) phosphorylation. Somatic PIK3CA mutations were detected in 52.4% of 42 EECs and 33.3% of 66 NEECs. Half (29 of 58) of all nonsynonymous PIK3CA mutations were in exons 1-7 and half were in exons 9 and 20. The exons 1-7 mutations localized to the ABD, ABD-RBD linker and C2 domains of p110α. Within these regions, Arg88, Arg93, Gly106, Lys111, Glu365, and Glu453, were recurrently mutated; Arg88, Arg93, and Lys111 formed mutation hotspots. The p110α-R93W, -G106R, -G106V, -K111E, -delP449-L455, and -E453K mutants led to increased levels of phospho-AKT(Ser473) compared to wild-type p110α. Overall, 62% of exons 1-7 PIK3CA mutants and 64% of exons 9-20 PIK3CA mutants were activating; 72% of exon 1-7 mutations have not previously been reported in endometrial cancer. Our study identified a new subgroup of endometrial cancer patients with activating mutations in the amino-terminal domains of p110α; these patients might be appropriate for consideration in clinical trials of targeted therapies directed against the PI3K pathway. ©2011 AACR.

  16. A unique spectrum of somatic PIK3CA (p110α) mutations within primary endometrial carcinomas

    PubMed Central

    Rudd, Meghan L.; Price, Jessica C.; Fogoros, Sarah; Godwin, Andrew K.; Sgroi, Dennis C.; Merino, Maria J.; Bell, Daphne W.

    2011-01-01

    Purpose The goal of this study was to comprehensively define the incidence of mutations in all exons of PIK3CA in both endometrioid endometrial cancer (EEC) and non-endometrioid endometrial cancer (NEEC). Experimental design We resequenced all coding exons of PIK3CA and PTEN, and exons 1 and 2 of KRAS, from 108 primary endometrial tumors. Somatic mutations were confirmed by sequencing matched normal DNAs. The biochemical properties of a subset of novel PIK3CA mutations were determined by exogenously expressing wildtype and mutant constructs in U2OS cells and measuring levels of AKTSer473 phosphorylation. Results Somatic PIK3CA mutations were detected in 52.4% of 42 EECs and 33.3% of 66 NEECs. Half (29 of 58) of all nonsynonymous PIK3CA mutations were in exons 1–7 and half were in exons 9 and 20. The exons 1–7 mutations localized to the ABD, ABD-RBD linker and C2 domains of p110α. Within these regions, Arg88, Arg93, Gly106, Lys111, Glu365, and Glu453, were recurrently mutated; Arg88, Arg93 and Lys111 formed mutation hotspots. The p110α-R93W, -G106R, -G106V, -K111E, -delP449-L455, and -E453K mutants led to increased levels of phospho-AKTSer473 compared to wild-type p110α. Overall, 62% of exons 1–7 PIK3CA mutants and 64% of exon 9–20 PIK3CA mutants were activating; 72% of exon 1–7 mutations have not previously been reported in endometrial cancer. Conclusions Our study identified a new subgroup of endometrial cancer patients with activating mutations in the amino-terminal domains of p110α; these patients might be appropriate for consideration in clinical trials of targeted therapies directed against the PI3K pathway. PMID:21266528

  17. Prolonged survival among women with BRCA germline mutations and advanced endometrial cancer: a case series.

    PubMed

    Kwon, J S; Lenehan, J; Carey, M; Ainsworth, P

    2008-01-01

    It is unclear if BRCA mutation carriers diagnosed with advanced endometrial cancer have a better prognosis compared to sporadic cases. From a population database of BRCA1 and 2 mutation carriers in Southwestern Ontario, Canada, we identified three women with advanced-stage endometrial cancer. They were 57, 59, and 64 years of age, and of English/Scottish, Ashkenazi Jewish, and English heritage, respectively. They had different mutations in BRCA1 (Q1240X:C3837T; 68_69delAG; 1961delA). One had a sarcomatoid carcinoma and two had uterine papillary serous carcinoma. All had stage IVB disease, with surgery followed by adjuvant chemotherapy and/or radiotherapy. Follow-up has ranged from 3.3 to 14.6 years. They are still alive and well with no evidence of recurrent disease. This observation raises the question as to whether BRCA mutations may be associated with a better prognosis in patients with advanced endometrial cancer.

  18. The role of fulvestrant in endometrial cancer.

    PubMed

    Bogliolo, Stefano; Cassani, Chiara; Dominoni, Mattia; Orlandini, Anna; Ferrero, Simone; Iacobone, Anna Daniela; Viazzo, Franco; Venturini, Pier Luigi; Spinillo, Arsenio; Gardella, Barbara

    2017-05-01

    Endometrial cancer is the most common malignancy of the female genital tract in industrialized countries. The traditional treatment of endometrial cancer is based on a surgical approach. In recent years, systemic endocrine therapy has demonstrated good efficacy in recurrent or metastatic setting, delaying progression, ameliorating quality of life and palliating symptoms. Areas covered: Phase I and II studies on selective estrogen receptor down-regulators used for the treatment of endometrial cancer treatment have been reviewed. The pharmacokinetic and pharmacodynamic features of selective receptor down-regulators have been also investigated. Expert opinion: Selective estrogen receptor down-regulators may exhibit clinical efficacy in the treatment of gynecological malignancies due to their pure estrogen receptor antagonist properties. However, up to now data are still limited and some unsolved questions remain. Fulvestrant has poor oral bioavailability and low pharmacodynamic characteristics. Further trials are required to examine new selective estrogen receptor down-regulator agents with better pharmacodynamic and pharmacokinetic profiles.

  19. Endometrial stem cells in regenerative medicine.

    PubMed

    Verdi, Javad; Tan, Aaron; Shoae-Hassani, Alireza; Seifalian, Alexander M

    2014-01-01

    First described in 2004, endometrial stem cells (EnSCs) are adult stem cells isolated from the endometrial tissue. EnSCs comprise of a population of epithelial stem cells, mesenchymal stem cells, and side population stem cells. When secreted in the menstrual blood, they are termed menstrual stem cells or endometrial regenerative cells. Mounting evidence suggests that EnSCs can be utilized in regenerative medicine. EnSCs can be used as immuno-modulatory agents to attenuate inflammation, are implicated in angiogenesis and vascularization during tissue regeneration, and can also be reprogrammed into induced pluripotent stem cells. Furthermore, EnSCs can be used in tissue engineering applications and there are several clinical trials currently in place to ascertain the therapeutic potential of EnSCs. This review highlights the progress made in EnSC research, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo.

  20. Endometrial stem cells in regenerative medicine

    PubMed Central

    2014-01-01

    First described in 2004, endometrial stem cells (EnSCs) are adult stem cells isolated from the endometrial tissue. EnSCs comprise of a population of epithelial stem cells, mesenchymal stem cells, and side population stem cells. When secreted in the menstrual blood, they are termed menstrual stem cells or endometrial regenerative cells. Mounting evidence suggests that EnSCs can be utilized in regenerative medicine. EnSCs can be used as immuno-modulatory agents to attenuate inflammation, are implicated in angiogenesis and vascularization during tissue regeneration, and can also be reprogrammed into induced pluripotent stem cells. Furthermore, EnSCs can be used in tissue engineering applications and there are several clinical trials currently in place to ascertain the therapeutic potential of EnSCs. This review highlights the progress made in EnSC research, describing their mesodermal, ectodermal, and endodermal potentials both in vitro and in vivo. PMID:25097665

  1. Multivariate analysis of endometrial tissue fluorescence spectra

    NASA Astrophysics Data System (ADS)

    Vaitkuviene, Aurelija; Auksorius, E.; Fuchs, D.; Gavriushin, V.

    2002-10-01

    Background and Objective: The detailed multivariate analysis of endometrial tissue fluorescence spectra was done. Spectra underlying features and classification algorithm were analyzed. An effort has been made to determine the importance of neopterin component in endometrial premalignization. Study Design/Materials and Methods: Biomedical tissue fluorescence was measured by excitation with the Nd YAG laser third harmonic. Multivariate analysis techniques were used to analyze fluorescence spectra. Biomedical optics group at Vilnius University analyzed the neopterin substance supplied by the Institute of Medical Chemistry and Biochemistry of Innsbruck University. Results: Seven statistically significant spectral compounds were found. The classification algorithm classifying samples to histopathological categories was developed and resulted in sensitivity of 80% and specificity 93% for malignant vs. hyperplastic and normal. Conclusions: Fluorescence spectra could be classified with high accuracy. Spectral variation underlying features can be extracted. Neopterin component might play an important role in endometrial hyperplasia development.

  2. Phytoestrogen intake and endometrial cancer risk.

    PubMed

    Horn-Ross, Pamela L; John, Esther M; Canchola, Alison J; Stewart, Susan L; Lee, Marion M

    2003-08-06

    The development of endometrial cancer is largely related to prolonged exposure to unopposed estrogens. Phytoestrogens (i.e., weak estrogens found in plant foods) may have antiestrogenic effects. We evaluated the associations between dietary intake of seven specific compounds representing three classes of phytoestrogens (isoflavones, coumestans, and lignans) and the risk of endometrial cancer. In a case-control study from the greater San Francisco Bay Area, we collected dietary information from 500 African American, Latina, and white women aged 35-79 years who were diagnosed with endometrial cancer between 1996 and 1999 and from 470 age- and ethnicity-matched control women identified through random-digit dialing. Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Isoflavone (OR = 0.59, 95% CI = 0.37 to 0.93 for the highest versus lowest quartile of exposure) and lignan (OR = 0.68, 95% CI = 0.44 to 1.1) consumptions were inversely related to the risk of endometrial cancer. These associations were slightly stronger in postmenopausal women (OR = 0.44, 95% CI = 0.26 to 0.77 and OR = 0.57, 95% CI = 0.34 to 0.97 for isoflavones and lignans, respectively). Obese postmenopausal women consuming relatively low amounts of phytoestrogens had the highest risk of endometrial cancer (OR = 6.9, 95% CI = 3.3 to 14.5 compared with non-obese postmenopausal women consuming relatively high amounts of isoflavones); however, the interaction between obesity and phytoestrogen intake was not statistically significant. Some phytoestrogenic compounds, at the levels consumed in the typical American-style diet, are associated with reduced risk of endometrial cancer.

  3. Pregnancy history and risk of endometrial cancer

    PubMed Central

    Pocobelli, Gaia; Doherty, Jennifer A.; Voigt, Lynda F.; Beresford, Shirley A.; Hill, Deirdre A.; Chen, Chu; Rossing, Mary Anne; Holmes, Rebecca S.; Noor, Zorawar S.; Weiss, Noel S.

    2011-01-01

    Background Epidemiologic studies are consistent in finding that women who have had at least one birth are less likely to develop endometrial cancer. Less clear is whether timing of pregnancies during reproductive life influences risk, and the degree to which incomplete pregnancies are associated with a reduced risk. Methods We evaluated pregnancy history in relation to endometrial cancer risk using data from a series of four population-based endometrial cancer case-control studies of women 45–74 years of age (1,712 cases and 2,134 controls) during 1985–2005 in western Washington State. Pregnancy history and information on other potential risk factors were collected by in-person interviews. Results Older age at first birth was associated with a reduced risk of endometrial cancer after adjustment for number of births and age at last birth (test for trend P = 0.004). The odds ratio comparing women at least 35 years of age at their first birth with those younger than 20 years was 0.34 (95% confidence interval = 0.14–0.84). Age at last birth was not associated with risk after adjustment for number of births and age at first birth (test for trend P = 0.830). Overall, a history of incomplete pregnancies was not associated with endometrial cancer risk to any appreciable degree. Conclusions In this study, older age at first birth was more strongly associated with endometrial cancer risk than was older age at last birth. To date, there remains some uncertainty in the literature on this issue. PMID:21691206

  4. Pregnancy after endometrial ablation: a systematic review.

    PubMed

    Kohn, J R; Shamshirsaz, A A; Popek, E; Guan, X; Belfort, M A; Fox, K A

    2017-09-27

    Pregnancies have been reported after endometrial ablation but there is little data regarding subsequent pregnancy outcomes. To review systematically the available evidence regarding pregnancy outcomes after endometrial ablation, in order to equip physicians effectively to counsel women considering endometrial ablation. MEDLINE, Embase, Cochrane, and ClinicalTrials.gov were searched through January 2017. Published and unpublished literature in any language describing pregnancy after endometrial ablation or resection was eligible. Data about preconception characteristics and pregnancy outcomes were extracted and analysed according to study design of source and pregnancy viability. We identified 274 pregnancies from 99 sources; 78 sources were case reports. Women aged 26-50 years (mean 37.5 ± 5 years) conceived a median of 1.5 years after ablation (range: 3 weeks prior to 13 years after). When reported, 80-90% had not used contraception. In all, 85% of pregnancies from trial/observational studies ended in termination, miscarriage or ectopic pregnancy. Pregnancies that continued (case report and non-case report sources) had high rates of preterm delivery, caesarean delivery, caesarean hysterectomy, and morbidly adherent placenta. Case reports also frequently described preterm premature rupture of membranes, intrauterine growth restriction, intrauterine fetal demise, uterine rupture, and neonatal demise. An unexpectedly high rate of pregnancy complications is reported in the available literature (which may reflect publication bias) and high-quality evidence is lacking. However, based on the existing evidence, women undergoing endometrial ablation should be informed that subsequent pregnancy may have serious complications and should be counselled to use reliable contraception after the procedure. Systematic review - pregnancies reported after endometrial ablation have an increased risk of adverse outcomes. © 2017 Royal College of Obstetricians and Gynaecologists.

  5. Metformin for endometrial hyperplasia: a Cochrane protocol

    PubMed Central

    Clement, Naomi S; Oliver, Thomas R W; Shiwani, Hunain; Saner, Juliane R F; Mulvaney, Caroline A; Atiomo, William

    2016-01-01

    Introduction Endometrial hyperplasia is a precancerous lesion of the endometrium, commonly presenting with uterine bleeding. If managed expectantly, it frequently progresses to endometrial carcinoma, rates of which are increasing dramatically worldwide. However, the established treatment for endometrial hyperplasia (progestogens) involves multiple side effects and leaves the risk of recurrence. Metformin is the most commonly used oral hypoglycaemic agent in type 2 diabetes mellitus. It has also been linked to the reversal of endometrial hyperplasia and may therefore contribute to decreasing the prevalence of endometrial carcinoma without the fertility and side effect consequences of current therapies. However, the efficacy and safety of metformin being used for this therapeutic target is unclear and, therefore, this systematic review will aim to determine this. Methods and analysis We will search the following trials and databases with no language restrictions: Cochrane Gynaecology and Fertility Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; EBSCO Cumulative Index to Nursing and Allied Health Literature; PubMed; Google Scholar; ClinicalTrials.gov; the WHO International Trials Registry Platform portal; OpenGrey and the Latin American and Caribbean Health Sciences Literature (LILACS). We will include randomised controlled trials (RCTs) of use of metformin compared with a placebo or no treatment, conventional medical treatment (eg, progestogens) or any other active intervention. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. Trial authors will be contacted for additional data. The primary review outcome is the regression of endometrial hyperplasia histology towards normal histology. Secondary outcomes include hysterectomy rate; abnormal uterine bleeding; quality of life scores and adverse reactions to treatments. Ethics and dissemination

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

    ClinicalTrials.gov

    2017-09-18

    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

  7. Effects of adipocyte-secreted factors on decidualized endometrial cells: modulation of endometrial receptivity in vitro.

    PubMed

    Gamundi-Segura, Silvia; Serna, Jose; Oehninger, Sergio; Horcajadas, Jose A; Arbones-Mainar, Jose M

    2015-09-01

    Obesity is defined as an excessive accumulation of adipose tissue that may lead to health complications. Mounting evidence indicates that obesity has a negative impact on fertility. Yet, the link between adipose tissue biology and infertility remains unclear. We aimed to investigate the communication between the adipose tissue and the reproductive system and the importance of this cross talk for the development of a receptive endometrium. To that end, we generated an in vitro model with endometrial and adipocyte cell lines. Sexual hormones, progesterone and estradiol, were used to decidualize endometrial cells and sensitize adipocytes. Decidualization produced a simultaneous increase of adipokine receptors in endometrial cells paralleling changes in their receptivity status. Furthermore, sensitization of 3T3-L1 adipocytes increased mRNA levels of leptin and resistin and decreased the expression of adiponectin and chemerin levels. This was accompanied by increased isoproterenol-induced lipolysis and reduced insulin-stimulated glucose uptake. Lastly, conditioned culture medium of those sensitized adipocytes was used to feed endometrial cells. This treatment resulted in (i) upregulation of genes previously identified as positive regulators of endometrial receptivity, such as leukemia inhibitory factor and glutathione peroxidase 3, and (ii) downregulation of interleukin-15 and mucin1, both genes negatively related with endometrial receptivity. Our results indicate that the endocrine communication between adipose tissue and the reproductive system is bidirectional and stress the importance of the adipose tissue to modulate the reproductive fitness.

  8. Endometrial Cancer in Hospital Universiti Sains Malaysia.

    PubMed

    Wan-Nor-Asyikeen, Wan Adnan; Siti-Azrin, Ab Hamid; Jalil, Nur Asyilla Che; Othman, Nor Hayati; Zain, Anani Aila Mat

    2016-01-01

    Endometrial cancer is the most common gynecological malignancy among females worldwide, approximately 320,000 women being diagnosed with the disease each year and 76,000 dying. To date, there is limited knowledge of endometrial cancer in Malaysia. To identify the epidemiological profile and prognostic factors of survival. A list of endometrial cancer patients in 2000-2011 was obtained from the hospital Record Department. Only cases confirmed by histopathology examination were included. We excluded those with incomplete medical records or referral cases. Simple and multiple Cox regression approaches were used for data analysis. Only 108 cases were included with a mean (SD) age of 62.7 (12.3) years, with 87.0% Malay ethnicity. Grade of cancer was: 29.1% grade 1, 43.7% grade 2 and 27.2% grade 3. The majority of patients had non-endometrioid type (60.2%), with myometrial invasion (82.2%) and lymphovascular invasion (57.3%). The significant prognostic factors were age (HR 1.05; 95% CI: 1.02, 1.08, p=0.002) and having lymphovascular invasion (HR 2.15; 95% CI: 1.08, 4.29; p=0.030). Endometrial cancer patients should be diagnosed earlier to reduce the risk of mortality. The public should be given education on the signs and symptoms of the disease.

  9. 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) Classification. Class II. The special controls for this device are: (1) FDA's: (i) “Use of International Standard...) Sterility Review Guidance of 2/12/90 (K90-1),” (2) Labeling: (i) Indication: Only to evaluate...

  10. Molecular Biology and Prevention of Endometrial Cancer

    DTIC Science & Technology

    2009-07-01

    of the oral contraceptive pill (OCP). Project 1: Objectives completed and data previously submitted with 2004 report. Data published this past year...molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive (OC...not been altered appreciably. Despite the known protective effect of oral contraceptives , little has been learned regarding the underlying mechanism

  11. [Radiotherapy of cervix and endometrial carcinoma].

    PubMed

    Barillot, I; Haie-Méder, C; Charra Brunaud, C; Peignaux, K; Kerr, C; Thomas, L

    2016-09-01

    External irradiation and brachytherapy still have a major place in the treatment of cervix and endometrial carcinoma. This review presents the French guidelines in terms of preparation and choice of irradiation techniques of these gynecological malignancies. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  12. Absence of MGMT promoter methylation in endometrial cancer

    PubMed Central

    Rimel, BJ; Huettner, Phyllis; Powell, Matthew A.; Mutch, David G.; Goodfellow, Paul J.

    2009-01-01

    Objective O6 –methylguanine-DNA methyltransferase (MGMT) acts to repair DNA damaged by alkylation of guanine residues. MGMT promoter methylation and gene silencing is seen in a variety of cancers and pre-cancerous changes [1-3]. The loss of MGMT activity and promoter methylation is associated with increased sensitivity to alkylating agents and is a favorable prognostic indicator in gliomas [4-6]. We sought to determine if MGMT promoter methylation plays a role in endometrial cancer. Methods One hundred and twenty primary endometrial cancers were analyzed for MGMT promoter methylation by combined bisulfite restriction analysis (COBRA). The cohort included 77 endometrioid endometrial cancers, 43 endometrial tumors of adverse histologic type, and 6 endometrial cancer cell lines. Twenty-one endometrioid and mixed endometrioid ovarian cancers were also analyzed. A subset of the primary tumors was analyzed for MGMT expression by immunohistochemistry. Results No MGMT promoter methylation was seen in the 120 endometrial cancers evaluated or the 6 endometrial cancer cell lines. One of the 21 endometrioid ovarian cancers showed methylation. Immunohistochemistry revealed moderate to high level expression of MGMT in the primary endometrial tumors. Conclusion MGMT promoter methylation is an infrequent event in endometrial cancer. MGMT expression and the ability to repair damaged alkylguanine residues could in part explain the limited response of endometrial tumors to alkylating chemotherapy. PMID:18973931

  13. Endometrial polyp surveillance in premenopausal breast cancer patients using tamoxifen

    PubMed Central

    Jeon, Se Jeong; Lee, Jae Il; Kim, Hee Seung; Kim, Jae Weon; Park, Noh Hyun; Song, Yong Sang

    2017-01-01

    Objective To describe the endometrial pathologic lesions in premenopausal breast cancer patients with a history of tamoxifen (TMX) use. Methods We retrospectively reviewed the medical records of 120 premenopausal breast cancer patients with a history of TMX use that had undergone a gynecological examination. Results Among 120 patients, 44.2% (n=53) were asymptomatic with an endometrial thickness ≥5 mm, as assessed by transvaginal ultrasonography. Of the patients that reported abnormal uterine bleeding, 5% (n=6) had an endometrial thickness <5 mm and 20% (n=24) had an endometrial thickness ≥5 mm by transvaginal ultrasonography. The final group of patients were asymptomatic, but showed an abnormal endometrial lesion, such as an endometrial polyp, by transvaginal ultrasonography (30.8%, n=37). Of the 56 benign lesions that were histologically reviewed, 50 (41.7%) were endometrial polyps, 3 (2.5%) were submucosal myomas, 2 (1.7%) were endometrial hyperplasias, and 1 (0.8%) was chronic endometritis. There were 64 (53.3%) other non-pathologic conditions, including secreting, proliferative, and atrophic endometrium, or in some cases, there was insufficient material for diagnosis. In our data, only one case was reported as a complex hyperplasia without atypia arising from an endometrial polyp, and one patient was diagnosed with endometrioid adenocarcinoma. Conclusion For premenopausal breast cancer patients with a history of TMX use, the majority of the patients were asymptomatic, and endometrial polyps were the most common endometrial pathology observed. Therefore, we believe that endometrial assessment before starting TMX treatment, and regular endometrial screening throughout TMX treatment, are reasonable suggestions for premenopausal breast cancer patients. PMID:28217668

  14. Endometrial study in patients with postmenopausal metrorrhagia

    PubMed Central

    de Merlo, Gaspar González; Mirasol, Esteban González; García, María Teresa Gómez; Parra, Carmen Ángel; Goy, Enrique Iglesias

    2016-01-01

    Introduction The aim of the study was to devise a strategy to diagnose malign endometrial pathologies (adenocarcinoma or atypical hyperplasia) that minimizes the number of invasive tests done (hysteroscopy, aspiration biopsy or curettage) with no loss of its detection efficiency. Material and methods We retrospectively studied the clinical histories of 779 postmenopausal women at the University Hospital Complex of Albacete, for whom an endometrial study had been done (hysteroscopy, aspiration biopsy or curettage) with a 1-year follow-up between 1 March 2006 and 31 March 2008. Results There were 77 cases of a malignant pathology (66 adenocarcinomas and 11 hyperplasias with atypia); 96.1% had metrorrhagia, and there were only 3 cases of asymptomatic patients (all 3 presented endometrial thickness of > 5 mm: 10, 12 and 15 mm). The sensitivity and specificity of the transvaginal ultrasound, with a 5 mm cut-off point to diagnose a malignant pathology, were 98.4% and 30.1%, respectively; 89.1% and 99.6%, respectively, for aspiration biopsy; 83.9% and 99.1%, respectively, for hysteroscopy without biopsy; and both were 100% for biopsy. Statistical significance was considered at p < 0.05 and confidence intervals were calculated at 95%. Conclusions In postmenopausal women with metrorrhagia, the first action to take is to do a transvaginal ultrasound, followed by en endometrial study, but only if the endometrium is irregular or endometrial thickness is ≥ 5 mm; in asymptomatic women, the cut-off point should be set at 10 mm. The immediate method of choice is an ambulatory biopsy. PMID:27279854

  15. CD82 expression alters with human endometrial cycles and affects the uterine endometrial receptivity in vitro.

    PubMed

    Wei, Xiaowei; Liu, Shuai; Wang, Xiaoqi; Yan, Qiu

    2012-03-01

    Embryo implantation is a process that requires both temporal and spatial synchronization of the uterine endometrium and the embryo, and the endometrium becomes receptive to the embryo during the window of implantation. Although the expression patterns of many implantation-related molecules change dynamically during this process, the impact of CD82 on endometrial receptivity has not been elucidated. By immunohistochemical staining, we found that CD82 levels rose from the proliferative phase to the secretory phase in human endometrium. Specifically, the highest level appeared in mid- and late-secretory phases. Consistently, RL95-2 cells, representative of high-receptive endometrial epithelium, expressed higher levels of CD82 than did HEC-1A cells, which are representative of low-receptive endometrial epithelium, as detected by reverse transcription-polymerase chain reaction, Western blot and immunofluorescence. Furthermore, progesterone up-regulated the expression of CD82 in both epithelial cell lines. Down-regulation of CD82 in RL95-2 cells by either CD82 siRNA transfection or treatment with a CD82 antibody significantly decreased the adhesion of human embryonic JAR cells to RL95-2 cell monolayers (P < 0.01) and inhibited the phosphorylation of focal adhesion kinase (FAK). In contrast, up-regulation of CD82 in HEC-1A cells by CD82 cDNA transfection promoted embryonic JAR cell adhesion to HEC-1A monolayers (P < 0.05) and activated the phosphorylation of FAK. In conclusion, the expression of CD82 increases in endometrial tissues during the window of embryo implantation, CD82 expression affects endometrial receptivity of the uterine epithelial cells in vitro, and the FAK signaling pathway may be involved in this phenomenon. The correlation between CD82 and endometrial receptivity suggests that CD82 may serve as a potential marker of endometrial function.

  16. 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.

  17. Endometrial adenocarcinoma in a 13-year-old girl

    PubMed Central

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

    2016-01-01

    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. PMID:27004208

  18. 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.

  19. MORPHOLOGICAL PATTERN OF ENDOMETRIAL BIOPSIES IN SOUTHWESTERN NIGERIA

    PubMed Central

    Abdullahi, YM; Ajani, MA; Iyapo, O; Aramide, KO; Okolo, CA; Akang, EEU

    2016-01-01

    Background: Endometrium remains the most sensitive indicator of ovarian function and endometrial biopsy is one of the diagnostic procedures in endometrial pathology. The current study was carried out to examine the morphological pattern of endometrial biopsies in Ibadan, South-western Nigeria and compare the results with similar studies. Method: A retrospective study was undertaken to review all cases of endometrial biopsies received in the Department of Pathology, University College Hospital, Ibadan between January 1999 and December 2008. The patients' data were retrieved from the surgical pathology daybooks and Histology Request forms. The neoplastic lesions were classified according to 2003 World Health Organization classification for endometrial neoplasms. Results: A total of 2,444 cases of endometrial biopsies were received during the 10-year study period. The functional endometrial changes were the most common histopathological diagnostic category, accounting for 53.8% (1035) of cases. Other pathological diagnoses included endometritis (7.8%), simple endometrial hyperplasia (5.8%), partial hydatidiform mole (2.3%), complete hydatidiform mole (2.1%) and malignant neoplastic lesions (3.9%). Infertility was the most common (57%) indication for endometrial biopsies followed by uterine bleeding (33%) while the least common clinical indication were the menstrual disorders (10%). Conclusion: The functional endometrial changes account for the highest morphological patterns while malignant lesions account for the least pattern of the endometrial biopsies evaluated for etiological basis of infertility, uterine bleeding and menstrual disorders in Ibadan. Infertility was the commonest indication for endometrial biopsies while the least common clinical indication was menstrual disorders. PMID:28337096

  20. Factors affecting intrauterine contraceptive device performance. I. Endometrial cavity length.

    PubMed

    Hasson, H M; Berger, G S; Edelman, D A

    1976-12-15

    The relationship of endometrial cavity length to intrauterine contraceptive device (IUD) performance was evaluated in 319 patients wearing three types of devices. The rate of events, defined as pregnancy, expulsion, or medical removal, increased significantly when the length of the IUD was equal to, exceeded, or was shorter by two or more centimeters than the length of the endometrial cavity. Total uterine length was found to be a less accurate prognostic indicator of IUD performance than endometrial cavity length alone.

  1. Post-Ablation Endometrial Carcinoma (PAEC) Following Radiofrequency Endometrial Ablation: A Case Report and Its Implications for Management of Endometrial Ablation Failures.

    PubMed

    Wortman, Morris; Dawkins, Josette C

    2016-10-26

    Endometrial ablation (EA) has become one of the most commonly performed gynecologic procedures in the United States and other developed countries. Global endometrial ablation (GEA) devices have supplanted resectoscopic ablation primarily because they have brought with them technical simplicity and unprecedented safety. These devices, all of which received FDA approval between 1997 and 2001, are typically used to treat abnormal uterine bleeding (AUB) in premenopausal women. Several million women in the US who have undergone a previous EA procedure are about to enter the risk pool for the development of endometrial cancer (EC). Ours is the 18th reported case of post-ablation endometrial carcinoma (PAEC) in the English literature. This case underscores the diagnostic challenges faced in evaluating women with a history of a previous EA who cannot be properly evaluated with conventional techniques such as endometrial biopsy and sonohysterography.

  2. PTEN sequence analysis in endometrial hyperplasia and endometrial carcinoma in Slovak women.

    PubMed

    Gbelcová, H; Bakeš, P; Priščáková, P; Šišovský, V; Hojsíková, I; Straka, Ľ; Konečný, M; Markus, J; D'Acunto, C W; Ruml, T; Böhmer, D; Danihel, Ľ; Repiská, V

    2015-01-01

    Phosphatase and tensin homolog (PTEN) is a protein that acts as a tumor suppressor by dephosphorylating the lipid second messenger phosphatidylinositol 3,4,5-trisphosphate. Loss of PTEN function has been implicated in the pathogenesis of a number of different tumors, particularly endometrial carcinoma (ECa). ECa is the most common neoplasia of the female genital tract. Our study evaluates an association between the morphological appearance of endometrial hyperplasia and endometrial carcinoma and the degree of PTEN alterations. A total of 45 endometrial biopsies from Slovak women were included in present study. Formalin-fixed and paraffin-embedded tissue samples with simple hyperplasia (3), complex hyperplasia (5), atypical complex hyperplasia (7), endometrioid carcinomas G1 (20) and G3 (5), and serous carcinoma (5) were evaluated for the presence of mutations in coding regions of PTEN gene, the most frequently mutated tumor suppressor gene in endometrial carcinoma. 75% of the detected mutations were clustered in exons 5 and 8. Out of the 39 mutations detected in 24 cases, 20 were frameshifts and 19 were nonsense, missense, or silent mutations. Some specimens harboured more than one mutation. The results of current study on Slovak women were compared to a previous study performed on Polish population. The two sets of results were similar.

  3. [Epidemiological survey on the relationship between obesity and endometrial cancer].

    PubMed

    Fujimoto, I; Hamada, T; Hasumi, K; Masubuchi, K; Sakamoto, G; Sugano, H

    1986-10-01

    Endometrial carcinoma is found more frequently in obese subjects. In this study, we evaluated the comparative risks of endometrial cancer relative to obesity indices calculated using the Brocas coefficient. From 1979 to 1983, we treated 185 patients with endometrial cancer at the Cancer Institute Hospital, Tokyo. Compared to nonobese subjects, those who exhibited an obesity index of 1.2 or more were found to have a relative risk value of 2.0 or more times that of normal subjects across all age groups. Based on these findings, it is suggested that a practical and effective preventive measure against endometrial cancer is to avoid becoming obese.

  4. GnRH antagonists may affect endometrial receptivity

    PubMed Central

    Rackow, Beth W.; Kliman, Harvey J.; Taylor, Hugh S.

    2009-01-01

    Study objective HOXA10 is an essential regulator of endometrial receptivity. To determine the effect of gonadotropin releasing hormone (GnRH) antagonists on endometrial receptivity we assessed endometrial HOXA10 expression in GnRH antagonist, GnRH agonist, and natural cycles. Design Prospective case-control study Setting University academic medical center Patients Nineteen subjects were included: 12 subjects underwent controlled ovarian hyperstimulation (COH) with recombinant follicle stimulating hormone (rFSH) and used either a GnRH antagonist or a GnRH agonist; 7 control subjects underwent natural cycles. Interventions Pipelle endometrial biopsies were obtained 11 days after human chorionic gonadotropin (hCG) administration or spontaneous luteinizing hormone (LH) surge in untreated cycles, respectively. Immunohistochemistry was used to assess HOXA10 protein expression in endometrial glands and stroma. Main outcome measure(s) Endometrial HOXA10 protein expression Results HOXA10 expression was significantly decreased in endometrial stromal cells in GnRH antagonist treated cycles compared with GnRH agonist treated cycles or natural cycle controls. There was no significant difference in glandular cell HOXA10 expression among the three groups. Conclusions Use of GnRH antagonists may be associated with impaired HOXA10 expression in endometrial stromal cells, and thus may affect endometrial receptivity. PMID:18410932

  5. Osteoporosis is less frequent in endometrial cancer survivors with hypertriglyceridemia.

    PubMed

    Hirasawa, Akira; Makita, Kazuya; Akahane, Tomoko; Yamagami, Wataru; Makabe, Takeshi; Yokota, Megumi; Horiba, Yuko; Ogawa, Mariko; Yanamoto, Shigehisa; Deshimaru, Rhota; Tominaga, Eiichiro; Banno, Kouji; Susumu, Nobuyuki; Aoki, Daisuke

    2015-01-01

    We previously reported an association between dyslipidemia and endometrial cancers. Osteoporosis is also reported to relate with some cancers. A common etiologic event has been proposed between dyslipidemia and osteoporosis. However, the pattern of interrelationships among dyslipidemia, osteoporosis and endometrial cancer is not well understood. To improve the quality of life of endometrial cancer survivors, these relationships should be determined. This study included 179 Japanese menopausal women who underwent bilateral salpingo-oophorectomy, including 114 women with incident endometrial cancer and 65 without endometrial cancer. The women were categorized according to dyslipidemia status. Bone mineral density was measured and compared between groups. Osteoporosis was statistically more frequent in women with hypertriglyceridemia who did not have endometrial cancer. In contrast, osteoporosis was statistically less frequent in women with hypertriglyceridemia who had endometrial cancer. In this cross-sectional study in a Japanese population, osteoporosis was associated with hypertriglyceridemia in post-menopausal women without endometrial cancer, but was less frequent in endometrial cancer survivors with hypertriglyceridemia.

  6. Influence of AKT on Progesterone Action in Endometrial Diseases1

    PubMed Central

    Lee, Irene I.; Kim, J. Julie

    2014-01-01

    ABSTRACT Progesterone plays an essential role in the maintenance of the endometrium; it prepares the endometrium for pregnancy, promotes decidualization, and inhibits estrogen-dependent proliferation. Progesterone function is often dysregulated in endometrial disease states. In addition, the PI3K/AKT signaling pathway is often overactive in endometrial pathologies and promotes the survival and proliferation of the diseased cells. Understanding how AKT influences progesterone action is critical in improving hormone-based therapies in endometrial pathologies. Here, we summarize recent studies investigating the crosstalk between the AKT pathway and progesterone receptor function in endometriosis and endometrial cancer. PMID:25100707

  7. Endometrial cancer: Not your grandmother's cancer.

    PubMed

    McAlpine, Jessica N; Temkin, Sarah M; Mackay, Helen J

    2016-09-15

    Worldwide, the incidence of endometrial carcinoma (EC) is rapidly increasing, and the highest disease burden is reported in North America and Western Europe. Although the prognosis remains good for patients with are diagnosed with early stage EC, for those with recurrent or metastatic disease, the options are few, and the median overall survival is short. It is imperative to gain a greater understanding of all aspects of EC, limit its effect on scarce health care resources and, more importantly, prevent this cancer from significantly impacting future generations of women. An exciting new era of endometrial cancer research and clinical management has begun that incorporates biologically and clinically relevant genomic and clinicopathologic parameters. Continued collaborative research efforts and funding are essential if we are to advance our understanding of this disease and improve clinical outcomes. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2787-2798. © 2016 American Cancer Society. © 2016 American Cancer Society.

  8. Endometrial microbiota-new player in town.

    PubMed

    Moreno, Inmaculada; Franasiak, Jason M

    2017-07-01

    Detection of bacteria with molecular techniques has enabled the study of low biomass microbiomes in tissues and organs previously considered sterile, such as the endometrium. Subsequently, an abnormal endometrial microbiota has been associated with implantation failure, pregnancy loss, and other gynecological and obstetrical conditions. Further investigation of the reproductive tract microbiome will allow for a better understanding of bacterial communities' role in both physiology and pathophysiology, which in turn impacts the ability to achieve pregnancy and maintain a healthy pregnancy. Here we review the current literature that surrounds the endometrial microbiome and highlight the importance of assessing it as a future tool for improving reproductive outcomes in infertile patients. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Endometrial cancer state of the science meeting.

    PubMed

    Kitchener, Henry C; Trimble, Edward L

    2009-01-01

    There is a pressing need to improve our understanding of endometrial cancer (EC) and uterine carcinosarcoma and to develop new treatment strategies to improve outcomes. In recognition of this, a State of the Science meeting on EC was held last November 28 and 29, 2006, in Manchester, United Kingdom. The meeting was cosponsored by the National Cancer Research Institute (UK), the National Cancer Institute (US), and the Gynecological Cancer Intergroup. The objectives of the meeting were as follows: 1. To review current knowledge and understanding of EC and its treatments. 2. To identify key issues for translational research and clinical trials. 3. To identify the most important trials for women with endometrial carcinoma and uterine carcinosarcoma, both those already underway or to be done, for which the Gynecological Cancer Intergroup might facilitate international cooperation.

  10. Polypoid uterine lesions mimicking endometrial stromal sarcoma.

    PubMed Central

    McCluggage, W G; Alderdice, J M; Walsh, M Y

    1999-01-01

    Two polypoid submucosal uterine lesions were examined histologically and immunohistochemically with monoclonal antibodies to desmin and alpha smooth muscle actin. One case comprised a leiomyoma and the other a polypoid form of adenomyosis. Both polyps had prolapsed through the external cervical os. The lesions had an ulcerated surface with focal areas of marked increased cellularity and pronounced vascularity throughout, such that they mimicked a low grade endometrial stromal sarcoma infiltrating the myometrium. The cellular areas showed diffuse positivity for desmin and alpha smooth muscle actin, confirming them to be of smooth muscle origin. The changes of marked hypercellularity and pronounced vascularity within polypoid submucosal uterine lesions have not been emphasised in published reports up to now. Pathologists should be aware of these morphological features in order to avoid misdiagnosis of such cases as endometrial stromal sarcomas. The changes described here are likely to be secondary to trauma associated with a polypoid lesion prolapsing through the external cervical os. Images PMID:10605413

  11. Microwave endometrial ablation for endometrial protection in women with breast cancer on adjuvant tamoxifen.

    PubMed

    Zhu, Yunshan; Yang, Jianhua

    2013-09-01

    The purpose of the current study was to determine the effectiveness of microwave endometrial ablation (MEA) in inhibiting the proliferative response of the endometrium in women with breast cancer who are treated with tamoxifen. In the before-after study, we treated 31 postmenopausal patients who had received adjuvant tamoxifen for 1 year or more with MEA, the endometrial changes were compared before and after MEA. After MEA, the thickness of the uterine lining was decreased significantly. No patient had recurrent endometrial polyps or abnormal vaginal bleeding during the follow-up period. MEA had a protective action against the uterine effects of tamoxifen for postmenopausal patients. MEA is a safe and effective minimally invasive treatment method for breast cancer patients treated with tamoxifen. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

  12. A New Diagnostic Test for Endometrial Cancer?

    PubMed Central

    Guralp, Onur; Sheridan, Susan M.; Harter, Josephine; Hinshaw, James Louis; Seo, Songwon; Hartenbach, Ellen M.; Lindheim, Steven; Stewar, Sarah; Kushner, David M.

    2014-01-01

    Objective During saline-infused sonohysterography (SIS), the distension fluid is typically discarded. If cytology analysis could identify those patients with endometrial cancer, many women would be spared from further procedures. Methods Thirty consecutive patients with clinical stage I or II endometrial adenocarcinoma were prospectively recruited preoperatively. Saline-infused sonohysterography was performed by instilling 5 mL of saline, withdrawing and sending for analysis. Saline was reinfused until complete SIS images were obtained and sent separately for cytology. Results Of the 30 women enrolled, SIS was technically successful in 29. Demographics included mean age (60.5 ± 6.99 years), body mass index (35.55 ± 8.18 kg/m2), endometrioid histology (76%), and grade (grade 1, 67%). Prestudy diagnostic method included biopsy (70%), dilatation and curettage (17%), and hysteroscopy (10%). Adequate cytology specimens were obtained in 66% of the 5mL flushes and 72% of the complete SIS collections. Of adequate specimens, the sensitivities to detect endometrial cancer for the 5-mL, complete, and combined fluid samples were 26% (95% confidence interval, 9%–51%), 36% (17%–59%), and 42% (22%–63%). Sensitivity based on the whole study sample (N = 30) was 33% (17%–53%). Statistical significance was not found in the association between a positive test and age, body mass index, grade, diagnostic method, or volume instilled or aspirated. Conclusions Most patients with early endometrial cancer can undergo SIS procedures with adequate cytology specimens obtained from distention media. However, the sensitivity is low, and refinements are necessary before utilizing as a diagnostic test. In cases with positive results, the patient may be able to avoid other costly and painful procedures. PMID:23881100

  13. Molecular genetic heterogeneity in undifferentiated endometrial carcinomas.

    PubMed

    Rosa-Rosa, Juan M; Leskelä, Susanna; Cristóbal-Lana, Eva; Santón, Almudena; López-García, Ma Ángeles; Muñoz, Gloria; Pérez-Mies, Belen; Biscuola, Michele; Prat, Jaime; Esther, Oliva E; Soslow, Robert A; Matias-Guiu, Xavier; Palacios, Jose

    2016-11-01

    Undifferentiated and dedifferentiated endometrial carcinomas are rare and highly aggressive subtypes of uterine cancer, not well characterized at a molecular level. To investigate whether dedifferentiated carcinomas carry molecular genetic alterations similar to those of pure undifferentiated carcinomas, and to gain insight into the pathogenesis of these tumors, we selected a cohort of 18 undifferentiated endometrial carcinomas, 8 of them with a well-differentiated endometrioid carcinoma component (dedifferentiated endometrioid carcinomas), and studied them by immunohistochemistry and massive parallel and Sanger sequencing. Whole-exome sequencing of the endometrioid and undifferentiated components, as well as normal myometrium, was also carried out in one case. According to The Cancer Genome Atlas classification, we distributed 95% of the undifferentiated carcinomas in this series as follows: (a) hypermutated tumors with loss of any mismatch repair protein expression and microsatellite instability (eight cases, 45%); (b) ultramutated carcinomas carrying mutations in the exonuclease domain of POLE (two cases, 11%); (c) high copy number alterations (copy-number high) tumors group exhibiting only TP53 mutations and high number of alterations detected by FISH (two cases, 11%); and (d) low copy number alterations (copy-number low) tumors with molecular alterations typical of endometrioid endometrial carcinomas (five cases, 28%). Two of the latter cases, however, also had TP53 mutations and higher number of alterations detected by FISH and could have progressed to a copy-number high phenotype. Most dedifferentiated carcinomas belonged to the hypermutated group, whereas pure undifferentiated carcinomas shared molecular genetic alterations with copy-number low or copy-number high tumors. These results indicate that undifferentiated and dedifferentiated endometrial carcinomas are molecularly heterogeneous tumors, which may have prognostic value.

  14. Immunohistochemical Profiling of Endometrial Serous Carcinoma.

    PubMed

    Chen, Wenqian; Husain, Arjumand; Nelson, Gregg S; Rambau, Peter F; Liu, Shuhong; Lee, Cheng-Han; Lee, Sandra; Duggan, Máire A; Köbel, Martin

    2017-03-01

    Endometrial serous carcinoma (ESC) is an aggressive neoplasm mainly seen in older women. The objective of this study was to refine immunohistochemical (IHC) panels for the differential diagnoses against endometrial endometrioid grade 3 (EC3), endometrial clear cell, and ovarian high-grade serous carcinoma as well as exploring the prognostic role of selected IHC markers. Fifty-two ESC from a single institution were assessed for 20 IHC markers, including ARID1A, CCNE1, CDKN2A, ERBB2, ESR1, HNF1B, FBXW7, IGF2BP3, MLH1, MSH2, MSH6, NAPSA, PAX8, PGR, PMS2, PTEN, TFF3, TP53, VIM, and WT1. ERBB2 chromogenic in situ hybridization was evaluated on tissue microarrays. Statistical analysis was performed. All ESC showed aberrant TP53, normal mismatch repair protein, and retained ARID1A and PTEN expression. ESR1 expression was present in 80% of ESC. A combination of TP53, PTEN, and CDKN2A had a sensitivity of 93.6% [95% confidence interval (CI), 84%-98%] and specificity of 87.8% (95% CI, 75%-95%) for ESC versus EC3. A combination of NAPSA and ESR1 had a sensitivity of 97.9% (95% CI, 89%-99%) and specificity of 72.2% (95% CI, 46%-90%) for ESC versus clear cell carcinoma. Absence of WT1 alone had a sensitivity of 66.0% (95% CI, 51%-79%) and specificity of 98.0% (95% CI, 94%-99%) for ESC versus ovarian high-grade serous carcinoma. Among all 52 ESCs, ERBB2 amplification was present in 23%, FBXW7 expression was absent in 10%, and CCNE1 was overexpressed in 59%, however, none were associated with prognosis. Our data support the value of IHC marker panels for histotyping of high-grade endometrial carcinomas.

  15. [The risk factors of endometrial cancer].

    PubMed

    Gerber, J; Sozański, L; Suchocki, S

    2001-12-01

    Authors presents the risk factors in endometrial cancer underlying such problems like hyperestrogenism, both external and internal caused by hormonally active ovarian masses, polycystic ovarian syndrome, adrenocortical hyperfunction and role of obesity in this pathological state. Other factors have been also described diabetes mellitus and hypertension, oral contraception, genetics factors, patient's obstetric history and other diseases where the increase of aromatization activity of androstendion to estron has been noted.

  16. Type II endometrial cancers: A case series

    PubMed Central

    Lobo, Flora D.; Thomas, Eliz

    2016-01-01

    Introduction: Endometrial carcinoma ranks 3rd in India among gynecological malignancies. Endometrial cancer (EC) can be classified into two distinct groups – type I and type II, based on histology, which differs in molecular, clinical and histopathological profiles. Type II is nonestrogen dependent, nonendometrioid, more aggressive and carries poor prognosis. Although type II cancers contribute only about 10% of EC incidence, they present at advanced age and cause approximately 50% recurrence and deaths with a low 5-year, overall survival rate. Type II EC are also characterized by genetic alterations in p53, human epidermal growth factor-2/neu, p16 and E-cadherin. Materials and Methods: Endometrial carcinomas diagnosed from endometrial biopsies and hysterectomy specimens received in the Department of Pathology, Kasturba Medical College, Mangalore, from January 2007 to June 2012 were included in the study. Clinicopathological analysis of the 84 cases of EC was done with emphasis on morphology. p53 immunostaining was performed in two cases of serous carcinoma. Results: Out of a total of 84 cases of EC, ten cases were of type II (11.9%). Out of which, eight were serous carcinoma (9.5%) and two clear cell (2.4%). p53 immunostain was strongly positive in the serous papillary carcinomas. The age of the patients ranged from 45 to 75 years. Myometrial invasion was more than half. Treatment was hysterectomy followed by aggressive chemotherapy. Conclusion: Of the type II EC, serous carcinoma is the most common type. Clinical presentation and prognosis differs in comparison to type I EC, thus the recognition of this type of EC is pivotal. PMID:27499593

  17. Global microwave endometrial ablation for menorrhagia treatment

    NASA Astrophysics Data System (ADS)

    Fallahi, Hojjatollah; Å ebek, Jan; Frattura, Eric; Schenck, Jessica; Prakash, Punit

    2017-02-01

    Thermal ablation is a dominant therapeutic option for minimally invasive treatment of menorrhagia. Compared to other energy modalities for ablation, microwaves offer the advantages of conformal energy delivery to tissue within short times. The objective of endometrial ablation is to destroy the endometrial lining of the uterine cavity, with the clinical goal of achieving reduction in bleeding. Previous efforts have demonstrated clinical use of microwaves for endometrial ablation. A considerable shortcoming of most systems is that they achieve ablation of the target by translating the applicator in a point-to-point fashion. Consequently, treatment outcome may be highly dependent on physician skill. Global endometrial ablation (GEA) not only eliminates this operator dependence and simplifies the procedure but also facilitates shorter and more reliable treatments. The objective of our study was to investigate antenna structures and microwave energy delivery parameters to achieve GEA. Another objective was to investigate a method for automatic and reliable determination of treatment end-point. A 3D-coupled FEM electromagnetic and heat transfer model with temperature and frequency dependent material properties was implemented to characterize microwave GEA. The unique triangular geometry of the uterus where lateral narrow walls extend from the cervix to the fundus forming a wide base and access afforded through an endocervical approach limit the overall diameter of the final device. We investigated microwave antenna designs in a deployed state inside the uterus. The impact of ablation duration on treatment outcome was investigated. Prototype applicators were fabricated and experimentally evaluated in ex vivo tissue to verify the simulation results and demonstrate proof-of-concept.

  18. Endometrial cancer and microsatellite instability status

    PubMed Central

    Vidugiriene, Jolanta; Valuckas, Konstantinas Povilas; Smailyte, Giedre; Uleckiene, Saule; Bacher, Jeff

    2015-01-01

    Microsatellite instability (MSI) is an important factor in the development of various cancers as an identifier of a defective DNA mismatch repair system. The objective of our study was to define the association between microsatellite instability status and traditional clinicopathologic characteristics of endometrioid type adenocarcinoma. Material and methods MSI status of endometrial cancer was examined by employing the Promega MSI Analysis System. This system uses 5 mononucleotide markers to identify MSI in tumour and normal tissue DNA (BAT-25, BAT-26, NR-21, NR-24, and MONO-27), and 2 pentanucleotide markers (Penta C and Penta D) for specimen identification. In this study, we investigated MSI status in 109 endometrial carcinomas. Results and conclusions One hundred (92%) of 109 endometrial cancers showed endometrioid type histology and only 9 (8%) non-endometrioid type. MSI-high was found in 17% (17/100) of endometrioid type adenocarcinomas, in 0% (0/9) of non-endometrioid carcinomas. Selected clinicopathologic parameters for endometrioid type adenocarcinomas were compared to the MSI status which was separated into two groups – MSI-high and MSI stable. The results showed that MSI-high status was related to clinicopathologic parameters such as deep myometrial invasion and higher histologic grade in endometrioid type adenocarcinomas.

  19. Integrated genomic characterization of endometrial carcinoma.

    PubMed

    Kandoth, Cyriac; Schultz, Nikolaus; Cherniack, Andrew D; Akbani, Rehan; Liu, Yuexin; Shen, Hui; Robertson, A Gordon; Pashtan, Itai; Shen, Ronglai; Benz, Christopher C; Yau, Christina; Laird, Peter W; Ding, Li; Zhang, Wei; Mills, Gordon B; Kucherlapati, Raju; Mardis, Elaine R; Levine, Douglas A

    2013-05-02

    We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

  20. The genomics and genetics of endometrial cancer

    PubMed Central

    O’Hara, Andrea J; Bell, Daphne W

    2012-01-01

    Most sporadic endometrial cancers (ECs) can be histologically classified as endometrioid, serous, or clear cell. Each histotype has a distinct natural history, clinical behavior, and genetic etiology. Endometrioid ECs have an overall favorable prognosis. They are typified by high frequency genomic alterations affecting PIK3CA, PIK3R1, PTEN, KRAS, FGFR2, ARID1A (BAF250a), and CTNNB1 (β-catenin), as well as epigenetic silencing of MLH1 resulting in microsatellite instability. Serous and clear cell ECs are clinically aggressive tumors that are rare at presentation but account for a disproportionate fraction of all endometrial cancer deaths. Serous ECs tend to be aneuploid and are typified by frequent genomic alterations affecting TP53 (p53), PPP2R1A, HER-2/ERBB2, PIK3CA, and PTEN; additionally, they display dysregulation of E-cadherin, p16, cyclin E, and BAF250a. The genetic etiology of clear cell ECs resembles that of serous ECs, but it remains relatively poorly defined. A detailed discussion of the characteristic patterns of genomic alterations that distinguish the three major histotypes of endometrial cancer is reviewed herein. PMID:22888282

  1. Integrated Genomic Characterization of Endometrial Carcinoma

    PubMed Central

    2013-01-01

    Summary We performed an integrated genomic, transcriptomic, and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumors and ~25% of high-grade endometrioid tumors have extensive copy number alterations, few DNA methylation changes, low ER/PR levels, and frequent TP53 mutations. Most endometrioid tumors have few copy number alterations or TP53 mutations but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A, KRAS and novel mutations in the SWI/SNF gene ARID5B. A subset of endometrioid tumors we identified had a dramatically increased transversion mutation frequency, and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy number low, and copy number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may impact post-surgical adjuvant treatment for women with aggressive tumors. PMID:23636398

  2. The epidemiology of endometrial and ovarian cancer.

    PubMed

    Cramer, Daniel W

    2012-02-01

    This review highlights similarities in the epidemiology of endometrial and ovarian cancer, including highly correlated incidence rates and similar risk factor profiles. Factors that decrease risk for both cancers include a late menarche, early age at first birth, giving birth and breastfeeding, and use of oral contraceptives. Short or irregular cycles and late menopause are associated with increased risk for both. Other risk factors that appear to operate in a similar direction include decreased risk associated with IUD use or a tubal ligation, and increased risk associated with obesity, lack of exercise, and use of talc powders in genital hygiene. Estrogen excess is proposed as the underlying mechanism for most endometrial cancers, whereas incessant ovulation has been suggested as the explanation for ovarian cancer. However, an increased number of estimated ovulatory cycles correlates directly with risk for both endometrial and ovarian cancer, suggesting that reproductive tissue turnover with an accumulation of PTEN or p53 mutations represents a possible common mechanism. An immune-based explanation involving mucin proteins represents another common mechanism that could explain additional risk factors. Maintenance of ideal weight, breastfeeding children, use of oral contraceptives, and avoidance of talc powders in genital hygiene are measures that could lower the risk for both types of cancer. Careful selection of patients for prophylactic oophorectomy for those women who are coming to hysterectomy for benign disease is an additional measure to consider for ovarian cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Implications of telomeres and telomerase in endometrial pathology.

    PubMed

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

    2017-03-01

    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. 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). 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. 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

  4. Nrf2 expression in endometrial serous carcinomas and its precancers.

    PubMed

    Chen, Ning; Yi, Xiaofang; Abushahin, Nisreen; Pang, Shujie; Zhang, Donna; Kong, Beihua; Zheng, Wenxin

    2010-12-24

    Endometrial serous carcinoma (ESC) is the most aggressive subtype of endometrial cancer. Its aggressive behavior and poor clinical outcome may be partially attributed to lack of early diagnostic markers and unclear patho-genesis. The transcription factor Erythroid-E2-related factor 2 (Nrf2) is a recently identified protein marker, which plays a role in carcinogenesis as well as responsible for poor prognosis of many human cancers. The aim of this study is to determine the Nrf2 expression in benign endometrium (n=28), endometrial cancers (n=122) as well as their precursor lesions (n=81) trying to see whether Nrf2 has any diagnostic usage and is potentially involved in endometrial carcinogenesis. The level of Nrf2 was evaluated by immunohistochemical (IHC) and verified by using Western blots. Among the malignant cases, Nrf2 was positive in 28 (68%) of 50 ESCs, which was significantly more than in 3 (6%) of 50 endometrioid carcinomas (p < 0.001) and 2 (13%) of 15 clear cell carcinomas (p = 0.001) and other histologic types of endometrial cancers. Among endometrial precursor lesions, both serous endometrial glandular dysplasia (EmGD, 40%) and serous endometrial intraepithelial carcinoma (EIC, 44%) showed a significantly higher Nrf2 expression than that in atypical endometrial hyperplasia or endometrial intraepithelial neoplasia (0%), clear cell EmGD (10%), and clear cell EIC (25%), respectively. We conclude that Nrf2 overexpression is closely associated with endometrial neoplasms with serous differentiation. Alteration of Nrf2 expression may represent one of the early molecular events in ESC carcinogenesis and overexpression of Nrf2 may used as a diagnostic marker in surgical pathology.

  5. Adjuvant radiotherapy for stage I endometrial cancer.

    PubMed

    Kong, Anthony; Johnson, Nick; Kitchener, Henry C; Lawrie, Theresa A

    2012-03-14

    This is an updated version of the original Cochrane review published in Issue 2, 2007. The role of radiotherapy (both pelvic external beam radiotherapy (EBRT) and vaginal intracavity brachytherapy (VBT)) in stage I endometrial cancer following hysterectomy remains controversial. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Specialised Register to end-2005 for the original review, and extended the search to January 2012 for the update. We included randomised controlled trials (RCTs) that compared post-operative adjuvant radiotherapy (either EBRT or VBT, or both) versus no radiotherapy or VBT in women with stage I endometrial cancer. Two review authors independently assessed trials and extracted data to a specifically designed data collection form. The primary outcome was overall survival. Secondary outcomes were endometrial cancer-related deaths, locoregional recurrence and distant recurrence. Meta-analyses were performed using Cochrane Review Manager Software 5.1. We included eight trials. Seven trials (3628 women) compared EBRT with no EBRT (or VBT), and one trial (645 women) compared VBT with no additional treatment. We considered six of the eight trials to be of a high quality. Time-to-event data were not available for all trials and all outcomes.EBRT (with or without VBT) compared with no EBRT (or VBT alone) for stage I endometrial carcinoma significantly reduced locoregional recurrence (time-to-event data: five trials, 2965 women; Hazard Ratio (HR) 0.36, 95% Confidence Interval (CI) 0.25 to 0.52; and dichotomous data: seven trials, 3628 women; Risk Ratio (RR) 0.33, 95% CI 0.23 to 0.47). This reduced risk of locoregional recurrence did not translate into improved overall survival (time-to-event data: five trials, 2,965 women; HR 0.99, 95% CI 0.82 to 1.20; and dichotomous data: seven trials, 3628 women; RR 0

  6. 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:…

  7. 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:…

  8. Autocrine Human Growth Hormone Stimulates Oncogenicity of Endometrial Carcinoma Cells

    PubMed Central

    Pandey, Vijay; Perry, Jo K.; Mohankumar, Kumarasamypet M.; Kong, Xiang-Jun; Liu, Shu-Min; Wu, Zheng-Sheng; Mitchell, Murray D.; Zhu, Tao; Lobie, Peter E.

    2008-01-01

    Recent published data have demonstrated elevated levels of human GH (hGH) in endometriosis and endometrial adenocarcinoma. Herein, we demonstrate that autocrine production of hGH can enhance the in vitro and in vivo oncogenic potential of endometrial carcinoma cells. Forced expression of hGH in endometrial carcinoma cell lines RL95-2 and AN3 resulted in an increased total cell number through enhanced cell cycle progression and decreased apoptotic cell death. In addition, autocrine hGH expression in endometrial carcinoma cells promoted anchorage-independent growth and increased cell migration/invasion in vitro. In a xenograft model of human endometrial carcinoma, autocrine hGH enhanced tumor size and progression. Changes in endometrial carcinoma cell gene expression stimulated by autocrine hGH was consistent with the altered in vitro and in vivo behavior. Functional antagonism of hGH in wild-type RL95-2 cells significantly reduced cell proliferation, cell survival, and anchorage-independent cell growth. These studies demonstrate a functional role for autocrine hGH in the development and progression of endometrial carcinoma and indicate potential therapeutic relevance of hGH antagonism in the treatment of endometrial carcinoma. PMID:18450952

  9. Surgical treatment of high stage endometrial cancer: current perspectives.

    PubMed

    Vitale, Salvatore Giovanni; Valenti, Gaetano; Gulino, Ferdinando Antonio; Cignini, Pietro; Biondi, Antonio

    2016-06-01

    Endometrial cancer is now the most common gynecologic malignancy. We investigate on new scientific evidences in endometrial cancer, particularly underlined updates in advanced endometrial cancer. Early stage endometrial cancer is the most frequent presentation; however, advanced endometrial cancer that occurs in 3-13 % of cases has bad prognosis. There are two types of endometrial cancer different in molecular pattern, therapeutic strategy and prognosis. Type I endometrial cancers develop in an environment of unopposed estrogen and often arise out of endometrial hyperplasia, characterized by mutations in the PTEN gene, K-ras, and microsatellite instability inception. Type II cancer is not an estrogen-related cancer, occurs predominantly in postmenopausal women, shows typical mutations in p53 and HER2/neu and has a poor prognosis. Preoperative characterization of the type's disease is an essential step for a right diagnosis and treatment. All patients should undergo to surgical staging, except those who are inoperable, according to FIGO recommendation. Surgical debulking, neoadjuvant chemotherapy and interval debulking can be strategy options.

  10. Threshold for endometrial sampling among postmenopausal patients without vaginal bleeding.

    PubMed

    Louie, Michelle; Canavan, Timothy P; Mansuria, Suketu

    2016-03-01

    To provide an optimum threshold for endometrial biopsy sampling among postmenopausal women without vaginal bleeding and an incidentally-found endometrial lining of above 4mm. A cohort of postmenopausal women (aged ≥50 years) who underwent pelvic ultrasonography at a tertiary US hospital for indications other than vaginal bleeding was retrospectively evaluated. Women were included if they had an endometrial lining of above 4mm. Logistic regression was performed to determine the probability of endometrial carcinoma and atypical hyperplasia at each increasing millimeter of endometrial thickness from 4 to 20mm. Among 462 women, carcinoma was identified in 9 (1.9%) and atypical hyperplasia in 7 (1.5%). An endometrial thickness of or above 14 mm was significantly associated with atypical hyperplasia (odds ratio 4.29; 95% confidence interval 1.30-14.20; P=0.02), with a negative predictive value of 98.3%. A thickness of or above 15 mm was associated with carcinoma (odds ratio 4.53; 95% confidence interval 1.20-17.20; P=0.03), with a negative predictive value of 98.5% and a 0.06% risk of cancer. Irrespective of conventional risk factors, an incidentally-found thickened endometrial lining of less than 15 mm might not warrant endometrial biopsy sampling among postmenopausal women without vaginal bleeding. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  11. 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

  12. Insights into human endometrial receptivity from transcriptomic and proteomic data.

    PubMed

    Haouzi, Delphine; Dechaud, Hervé; Assou, Said; De Vos, John; Hamamah, Samir

    2012-01-01

    The appreciation of endometrial receptivity is a crucial step in assisted reproductive technology as implantation failures are thought to result, in large part, from abnormal endometrial receptivity. Using emerging omics technologies, investigators have begun to define both molecular signatures and specific biomarkers of receptive endometrium. The aim of this review was to analyse the new perspectives brought to the appreciation of endometrial receptivity by transcriptomic and proteomic technologies, involving the analysis of gene- or protein-expression-profile shifts between the pre-receptive and receptive secretory stages and how they might lead to new strategies for endometrial receptivity assessments. The use of omics as molecular tools to determine the effects of stimulation protocols on endometrial gene expression and clinical outcomes has also been investigated.

  13. Personalized therapy in endometrial cancer: Challenges and opportunities

    PubMed Central

    Westin, Shannon N

    2012-01-01

    Early stage endometrial cancer is generally curable. However, progress in the treatment of advanced and recurrent endometrial cancer has been limited. This has led to a shift from the use of traditional chemotherapeutic agents and radiotherapy regimens to the promising area of targeted therapy, given the large number of druggable molecular alterations found in endometrial cancer. To maximize the effects of directed targeted therapy, careful molecular characterization of the endometrial tumor is necessary. This represents an important difference in the use of targeted therapy vs. traditional chemotherapy or radiation treatment. This review will discuss relevant pathways to target in endometrial cancer as well as the challenges that arise during development of a personalized oncology approach. PMID:22198566

  14. Endometrial cancer and obesity: epidemiology, biomarkers, prevention and survivorship.

    PubMed

    Fader, Amanda Nickles; Arriba, Lucybeth Nieves; Frasure, Heidi E; von Gruenigen, Vivian E

    2009-07-01

    Endometrial cancer is the most common gynecologic malignancy in the Western world and is strongly associated with obesity. Despite the fact that most cases are diagnosed in early, more favorable stages, endometrial cancer incidence and mortality rates are on the rise. Morbidly obese women with endometrial cancer are more likely to die of their co-morbidities and also of their cancers when compared to their leaner cohorts. Given the increasing rates of morbid obesity in the United States, it is essential to develop appropriate screening tools and guidelines to reduce cancer morbidity and death amongst this group. Through an analysis of the existing literature, we present a review of the epidemiologic trends in obesity and endometrial cancer, discuss the promising role of screening biomarker studies, review prevention efforts and modifiable risk factors, and ways in which health outcomes and quality of life for endometrial cancer survivors may be optimized.

  15. Validation of REM score to predict endometrial cancer in patients with ultrasound endometrial abnormalities: results of a new independent dataset.

    PubMed

    Plotti, Francesco; Capriglione, Stella; Terranova, Corrado; Montera, Roberto; Scaletta, Giuseppe; Lopez, Salvatore; Luvero, Daniela; Gianina, Antonelli; Aloisi, Alessia; Benedetti Panici, Pierluigi; Angioli, Roberto

    2017-05-01

    The risk of endometrial malignancy (REM) score is a model formulated in a previous single-center validation study, which has been shown to predict endometrial cancer in women with ultrasound endometrial abnormalities based on multiple features (clinical, ultrasound and laboratorial). The purpose of this study was to validate the performance of REM score in an external validation setting. A population-based database with patients, who underwent elective hysteroscopy for ultrasound endometrial abnormalities between 2013 and 2016 at Department of Obstetrics and Gynecology of Campus Bio-medico of Rome, was used. Starting from January 2013 to June 2016, 330 patients were enrolled for hysteroscopy. Thirty-two patients were excluded due to Asherman syndrome or cervical stenosis. Therefore, a total of 298 patients were considered for the analysis. Based on pathologic examination, 102 patients were found to have endometrial cancer, and 196 had benign endometrial disease. Using the predefined cutoff of 0.3185, identified in the previous publication, in this independent cohort of patients we correctly classified 93/102 patients with endometrial cancer and 187/196 with benign disease, reporting an overall sensitivity and specificity of 93.9 and 95.4% (PPV = 0.91, NPV = 0.95), respectively. REM score showed a high positive predictive value for endometrial cancer prediction. However, before REM score can be applied in daily clinical practice, data from randomized controlled trials are needed.

  16. Infrequent methylation of the DUSP6 phosphatase in endometrial cancer

    PubMed Central

    Chiappinelli, Katherine B.; Rimel, B. J.; Massad, L. Stewart; Goodfellow, Paul J.

    2010-01-01

    Objective Dual-specificity phosphatase six (DUSP6, MKP3, or PYST1) dephosphorylates phosphotyrosine and phosphothreonine residues on ERK-2 (MAPK1) to inactivate the ERK-2 kinase. DUSP6 is a critical regulator of the ERK signaling cascade and has been implicated as a tumor suppressor. DNA methylation in the first intron of DUSP6 abrogates expression in a subset of pancreatic cancers. We sought to determine whether DUSP6 was similarly silenced by methylation in endometrial cancer, a tumor type in which there is frequent activation of the ERK pathway. Methods 109 endometrial cancers were analyzed for DUSP6 methylation using combined bisulfite restriction analysis (COBRA). The cohort included 70 primary endometrioid endometrial cancers, 21 primary endometrial tumors of adverse histological types, and 18 endometrial cancer cell lines. Primary tumors, cell lines, and normal endometrial tissues were analyzed for DUSP6 mRNA levels using quantitative RT-PCR and pERK levels by Western blots and/ or immunohistochemistry. Results Methylation of the first intron of the DUSP6 gene was seen in 1/91 primary endometrial cancers investigated. The methylated tumor was also methylated at the more 5′ regulatory region of DUSP6. Q-RT-PCR revealed that DUSP6 transcript levels varied widely in primary endometrial tumors. DUSP6 mRNA levels did not correlate with pERK status in primary tumors, consistent with the existence of negative feedback loops activated by pERK that result in transcription of DUSP6. Conclusion DUSP6 methylation is a rare event in endometrial cancer. Silencing of the DUSP6 phosphatase is unlikely to contribute to constitutive activation of the ERK kinase cascade in endometrial cancer. PMID:20638106

  17. Infrequent methylation of the DUSP6 phosphatase in endometrial cancer.

    PubMed

    Chiappinelli, Katherine B; Rimel, B J; Massad, L Stewart; Goodfellow, Paul J

    2010-10-01

    Dual-specificity phosphatase six (DUSP6, MKP3, or PYST1) dephosphorylates phosphotyrosine and phosphothreonine residues on ERK-2 (MAPK1) to inactivate the ERK-2 kinase. DUSP6 is a critical regulator of the ERK signaling cascade and has been implicated as a tumor suppressor. DNA methylation in the first intron of DUSP6 abrogates expression in a subset of pancreatic cancers. We sought to determine whether DUSP6 was similarly silenced by methylation in endometrial cancer, a tumor type in which there is frequent activation of the ERK pathway. One hundred and nine endometrial cancers were analyzed for DUSP6 methylation using combined bisulfite restriction analysis (COBRA). The cohort included 70 primary endometrioid endometrial cancers, 21 primary endometrial tumors of adverse histological types, and 18 endometrial cancer cell lines. Primary tumors, cell lines, and normal endometrial tissues were analyzed for DUSP6 mRNA levels using quantitative RT-PCR and pERK levels by Western blots and/or immunohistochemistry. Methylation of the first intron of the DUSP6 gene was seen in 1/91 primary endometrial cancers investigated. The methylated tumor was also methylated at the more 5' regulatory region of DUSP6. Q-RT-PCR revealed that DUSP6 transcript levels varied widely in primary endometrial tumors. DUSP6 mRNA levels did not correlate with pERK status in primary tumors, consistent with the existence of negative feedback loops activated by pERK that result in transcription of DUSP6. DUSP6 methylation is a rare event in endometrial cancer. Silencing of the DUSP6 phosphatase is unlikely to contribute to constitutive activation of the ERK kinase cascade in endometrial cancer. Copyright © 2010 Elsevier Inc. All rights reserved.

  18. Adjuvant radiotherapy for stage I endometrial cancer

    PubMed Central

    Kong, Anthony; Johnson, Nick; Kitchener, Henry C; Lawrie, Theresa A

    2014-01-01

    Background This is an updated version of the original Cochrane review published in Issue 2, 2007. The role of radiotherapy (both pelvic external beam radiotherapy (EBRT) and vaginal intracavity brachytherapy (VBT)) in stage I endometrial cancer following hysterectomy remains controversial. Objectives To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. Search methods We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Specialised Register to end-2005 for the original review, and extended the search to January 2012 for the update. Selection criteria We included randomised controlled trials (RCTs) that compared post-operative adjuvant radiotherapy (either EBRTor VBT, or both) versus no radiotherapy or VBT in women with stage I endometrial cancer. Data collection and analysis Two review authors independently assessed trials and extracted data to a specifically designed data collection form. The primary outcome was overall survival. Secondary outcomes were endometrial cancer-related deaths, locoregional recurrence and distant recurrence. Meta-analyses were performed using Cochrane Review Manager Software 5.1. Main results We included eight trials. Seven trials (3628 women) compared EBRT with no EBRT (or VBT), and one trial (645 women) compared VBTwith no additional treatment. We considered six of the eight trials to be of a high quality. Time-to-event data were not available for all trials and all outcomes. EBRT (with or without VBT) compared with no EBRT (or VBT alone) for stage I endometrial carcinoma significantly reduced locoregional recurrence (time-to-event data: five trials, 2965 women; Hazard Ratio (HR) 0.36, 95% Confidence Interval (CI) 0.25 to 0.52; and dichotomous data: seven trials, 3628 women; Risk Ratio (RR) 0.33, 95% CI 0.23 to 0.47). This reduced risk of locoregional recurrence did not translate into improved overall survival (time-to-event data: five trials, 2

  19. Adjuvant radiotherapy for stage I endometrial cancer.

    PubMed

    Kong, Anthony; Johnson, Nick; Kitchener, Henry C; Lawrie, Theresa A

    2012-04-18

    This is an updated version of the original Cochrane review published in Issue 2, 2007. The role of radiotherapy (both pelvic external beam radiotherapy (EBRT) and vaginal intracavity brachytherapy (VBT)) in stage I endometrial cancer following hysterectomy remains controversial. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. We searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Specialised Register to end-2005 for the original review, and extended the search to January 2012 for the update. We included randomised controlled trials (RCTs) that compared post-operative adjuvant radiotherapy (either EBRTor VBT, or both) versus no radiotherapy or VBT in women with stage I endometrial cancer. Two review authors independently assessed trials and extracted data to a specifically designed data collection form. The primary outcome was overall survival. Secondary outcomes were endometrial cancer-related deaths, locoregional recurrence and distant recurrence. Meta-analyses were performed using Cochrane Review Manager Software 5.1. We included eight trials. Seven trials (3628 women) compared EBRT with no EBRT (or VBT), and one trial (645 women) compared VBTwith no additional treatment. We considered six of the eight trials to be of a high quality. Time-to-event data were not available for all trials and all outcomes.EBRT (with or without VBT) compared with no EBRT (or VBT alone) for stage I endometrial carcinoma significantly reduced locoregional recurrence (time-to-event data: five trials, 2965 women; Hazard Ratio (HR) 0.36, 95% Confidence Interval (CI) 0.25 to 0.52; and dichotomous data: seven trials, 3628 women; Risk Ratio (RR) 0.33, 95% CI 0.23 to 0.47). This reduced risk of locoregional recurrence did not translate into improved overall survival (time-to-event data: five trials, 2,965 women; HR 0.99, 95% CI 0.82 to1.20; and dichotomous data: seven trials, 3628 women; RR 0.98, 95

  20. Outpatient vaginal cuff brachytherapy for endometrial cancer.

    PubMed

    Petereit, D. G.; Tannehill, S. P.; Grosen, E. A.; Hartenbach, E. M.; Schink, J. C.

    1999-11-01

    Petereit DG, Tannehill SP, Grosen EA, Hartenbach EM, Schink JC. Outpatient vaginal cuff brachytherapy for endometrial cancer. The objective of this study was to determine the efficacy and complications of postoperative high-dose-rate (HDR) vaginal-cuff brachytherapy (VCB) in patients with endometrial carcinoma. Between August 1989 to September 1997, 191 patients were treated postoperatively after a total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH/BSO) with outpatient adjuvant HDR VCB for low-risk endometrial cancer (IB-84%, grade 1 or 2-96%). Patients were treated with 2 HDR fractions, delivered one week apart while under conscious sedation (16.2 Gy X 2 to the vaginal surface). All clinical endpoints were calculated using the Kaplan Meier method. The median time in the brachytherapy suite was 60 min in which no acute complications were observed. The 30-day morbidity and mortality rates were both 0%. With a median follow-up of 38 months (12-82 months), the 4-year survival, relapse-free survival, and vaginal-control rates were 95%, 98%, and 100%, respectively. One patient developed a colo-vaginal fistula at 5 years. Adjuvant HDR VCB in 2 outpatient insertions produced 100% vaginal control rates with minimal morbidity. The advantages of high dose-rate compared to low dose-rate vaginal brachytherapy include patient convenience, markedly shorter treatment times (1 h per insertion), and reduction in the cost and potential morbidity of hospitalization. HDR brachytherapy approach is a cost-effective alternative to either low-dose-rate brachytherapy or whole pelvic radiotherapy in carefully selected patients.

  1. Isolated humeral recurrence in endometrial carcinoma

    PubMed Central

    Devdas, Santosh Kumar; Digumarti, Leela; Digumarti, Raghunadharao; Patro, Kunha Charan; Nutakki, Ramakoteswararao

    2016-01-01

    Isolated skeletal metastasis in endometrial carcinoma at recurrence is very rare. We report a 52-year-old woman diagnosed to have FIGO Stage 1b, Grade 1 endometrioid adenocarcinoma, presenting with isolated distal humerus metastasis, 2 years after surgery and adjuvant radiotherapy for primary disease. Imaging, bone scintigraphy, and cytology confirmed the diagnosis of poorly differentiated metastatic adenocarcinoma. She was treated with local radiotherapy followed by six cycles of paclitaxel and carboplatin chemotherapy along with zoledronic acid, monthly. She is symptom-free after the treatment and at a first follow-up visit after 3 months. PMID:27688615

  2. Pre-operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding.

    PubMed

    Sowter, M C; Lethaby, A; Singla, A A

    2002-01-01

    Menorrhagia is one of the most common reasons for pre-menopausal women to be referred to a gynaecologist. Although medical therapy is generally the first approach, many women will eventually require or request a hysterectomy. Hysterectomy is associated with a significant in-patient hospital stay and a period of convalescence that makes it an unattractive and unnecessarily invasive option for many women. Hysteroscopic endometrial ablation or resection, and more recently "second generation" devices such as balloon or microwave ablation offer a day-case surgical alternative to hysterectomy for these women. They are also cheaper procedures than hysterectomy. Complete endometrial removal or destruction is one of the most important determinants of treatment success. Therefore surgery will be most effective if undertaken when endometrial thickness is less than four mm, in the immediate post-menstrual phase, however there are often difficulties in reliably arranging surgery for this time. The other option is the use of hormonal agents which induce endometrial thinning or atrophy prior to surgery. The most commonly evaluated agents have been goserelin (a GnRH analogue) and danazol. Progestogens and other GnRH analogues have also been studied although less data are available. It has been suggested that the use of these agents, particularly GnRH analogues, will reduce operating time, improve the intra-uterine operating environment, and reduce distension medium absorption (this is the fluid used to distend the uterine cavity during surgery). They may also result in a greater improvement in long term outcomes such as menstrual loss and dysmenorrhoea. To investigate the effectiveness of gonadotrophin-releasing hormone (GnRH) analogues, danazol, and progestogens, when used for endometrial thinning prior to endometrial destruction for menorrhagia, in improving the intra-uterine operating environment and treatment outcome after surgery. The Menstrual Disorders and Subfertility

  3. [Environmental and genetic risk factors for endometrial carcinoma].

    PubMed

    Sénéchal, Claire; Cottereau, Edouard; de Pauw, Antoine; Elan, Camille; Dagousset, Isabelle; Fourchotte, Virginie; Gauthier-Villars, Marion; Lae, Marick; Stoppa-Lyonnet, Dominique; Buecher, Bruno

    2015-03-01

    In France, endometrial cancer is at the first rank of gynecological cancers for cancer incidence, before ovarian and cervical cancers. In fact, the number of incident cases has been estimated to 7275 for the year 2012; the number of death due to endometrial cancer to 2025. This cancer is hormone-dependent and endogenous (reproductive factors) or exogenous (oral combined contraceptives, hormone replacement therapy) causes of exposition to estrogens are the major environmental risk factors for both types of endometrial cancers: type I or well-differentiated endometrioid adenocarcinomas; and type II including all other histological types: papillary serous adenocarcinomas, clear cell adenocarcinomas and carcinosarcomas, also known as malignant mixed Mullerian tumor, MMMT. Obesity, diabetes mellitus and adjuvant treatment of breast cancer with tamoxifen are also associated with an increased risk of endometrial cancer. Genetic factors may also be implicated in the pathogenesis of endometrial cancer either as "minor genetic factors" (susceptibility factors), which remain largely unknown and are responsible for the increased observed risk in relatives of women affected with endometrial cancer; or as major genetic factors responsible for hereditary forms and namely for Lynch syndrome whose genetic transmission is of autosomic dominant type. The appropriate recognition of Lynch syndrome is of critical importance because affected patients and their relatives should benefit from specific care. The aims of this review is to describe major environmental and genetic risk factors for endometrial cancer with specific attention to most recent advances in this field and to describe recommendations for care of at-risk women.

  4. 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

  5. Profiling the gene signature of endometrial receptivity: clinical results.

    PubMed

    Garrido-Gómez, Tamara; Ruiz-Alonso, María; Blesa, David; Diaz-Gimeno, Patricia; Vilella, Felipe; Simón, Carlos

    2013-03-15

    This article highlights the need for methods to objectively diagnose endometrial receptivity as a factor contributing to infertility in female patients. The correct identification of the appropriate window of implantation in a given patient, by using endometrial receptivity biomarkers, can help to prevent reproductive failure resulting from misplaced timing of the endometrial window of implantation (WOI). Although to date no single, clinically relevant morphologic, molecular, or histologic marker capable of indicating endometrial receptivity status has been identified, global transcriptomic analysis of human endometria performed in the last decade has given us insights into a genomic signature that is capable of identifying endometrial receptivity. As a consequence, a genomic tool named the Endometrial Receptivity Array (ERA), based on a customized microarray, was developed, and along with it a specially trained bioinformatic prediction computer algorithm was created to identify WOI timing in the endometrium. This tool has proven more accurate and consistent than histologic (Noyes) dating at identifying the personalized WOI day, thus leading to the new clinical concept of personalized ET on the optimum day of endometrial receptivity, identified individually case by case.

  6. Stromal p16 expression is significantly increased in endometrial carcinoma.

    PubMed

    Yoon, Gun; Koh, Chang Won; Yoon, Nara; Kim, Ji-Ye; Kim, Hyun-Soo

    2017-01-17

    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.

  7. Endometrial Samples From Postmenopausal Women: A Proposal for Adequacy Criteria.

    PubMed

    Sakhdari, Ali; Moghaddam, Parnian A; Liu, Yuxin

    2016-11-01

    Approximately 75% of endometrial cancer occurs in women older than 55 yr of age. Postmenopausal bleeding is often considered endometrial cancer until proven otherwise. One diagnostic challenge is that endometrial biopsy or curettage generally yields limited samples from elderly patients. There are no well-defined and unified diagnostic criteria for adequacy of endometrial samples. Pathologists who consider any sample including those lacking endometrial tissue as "adequate" run the risk of rendering false-negative reports; on the contrary, pathologists requiring ample endometrial glands along with stroma tend to designate a greater number of samples as "inadequate," leading to unnecessary follow-up. We undertook a quantitative study of 1768 endometrial samples from women aged 60 yr and older aiming to propose validated adequacy criteria for diagnosing or excluding malignancy. Using repeat-procedure outcomes as reference, we found that samples exceeding 10 endometrial strips demonstrated high negative predictive value close to 100%. Such samples can be scant, yet appear to be sufficient in excluding malignant conditions. When tissue diminished to <10 strips, negative predictive value dropped significantly to 81%. The risk of undersampled malignancy rose to 19%. Among 274 malignant cases, only 4 cases yielded limited tissue yet >10 strips. In conclusion, we propose 10 endometrial strips as the minimum for adequate samples from postmenopausal women. Applying such validated adequacy criteria will greatly reduce false-negative errors and avoid unnecessary procedures while ultimately improving diagnostic accuracy. Our criteria may serve as a reference point in unifying the pathology community on this important and challenging topic.

  8. 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

  9. A prospective investigation of coffee drinking and endometrial cancer incidence.

    PubMed

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

    2012-08-15

    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; P(trend) = 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 (P(interaction) = 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; P(trend) = 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.

  10. Obesity-associated endometrial and cervical cancers.

    PubMed

    Gu, Wenyi; Chen, Chen; Zhao, Kong-Nan

    2013-01-01

    Epidemiological studies have indicated that obesity (body mass index-BMI>30) and overweight (BMI>25) directly associated with risk of many cancers. The association of obesity with cancer risks may be explained by the alterations in the metabolism of endogenous hormones, production of specific proteins and cytokines, adipose related inflammatory reactions, and genetic factors. This review aims to illustrate the link between obesity and occurrence and prognosis of endometrial and cervical cancers. Convincing scientific evidence shows that nutrition and lifestyle factors initiate the development of obesity with excessive adipose tissues, which trigger production of hormones, cytokines and other factors to promote growth of cancer cells. Obese women with either endometrial or cervical cancer, especially in postmenopausal period, have shown a significantly higher mortality. This is mainly due to that the obese women are more vulnerable in cancer occurrence and they are more likely to miss routine cancer screening, putting them at a greater risk for delayed diagnosis of these cancers and deteriorate prognosis. Thus, healthcare providers should pay particular attention to this more vulnerable group of women.

  11. Contemporary Clinical Management of Endometrial Cancer

    PubMed Central

    Dinkelspiel, Helen E.; Wright, Jason D.; Lewin, Sharyn N.; Herzog, Thomas J.

    2013-01-01

    Although the contemporary management of endometrial cancer is straightforward in many ways, novel data has emerged over the past decade that has altered the clinical standards of care while generating new controversies that will require further investigation. Fortunately most cases are diagnosed at early stages, but high-risk histologies and poorly differentiated tumors have high metastatic potential with a significantly worse prognosis. Initial management typically requires surgery, but the role and extent of lymphadenectomy are debated especially with well-differentiated tumors. With the changes in surgical staging, prognosis correlates more closely with stage, and the importance of cytology has been questioned and is under evaluation. The roles of radiation in intermediate-risk patients and chemotherapy in high-risk patients are emerging. The therapeutic index of brachytherapy needs to be considered, and the best sequencing of combined modalities needs to balance efficacy and toxicities. Additionally novel targeted therapies show promise, and further studies are needed to determine the appropriate use of these new agents. Management of endometrial cancer will continue to evolve as clinical trials continue to answer unsolved clinical questions. PMID:23864861

  12. Therapeutic options for management of endometrial hyperplasia.

    PubMed

    Chandra, Vishal; Kim, Jong Joo; Benbrook, Doris Mangiaracina; Dwivedi, Anila; Rai, Rajani

    2016-01-01

    Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH.

  13. Adjuvant chemotherapy for advanced endometrial cancer.

    PubMed

    Galaal, Khadra; Al Moundhri, Mansour; Bryant, Andrew; Lopes, Alberto D; Lawrie, Theresa A

    2014-05-15

    Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective. To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV). We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials. Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer. Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software. We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data

  14. Therapeutic options for management of endometrial hyperplasia

    PubMed Central

    2016-01-01

    Endometrial hyperplasia (EH) comprises a spectrum of changes in the endometrium ranging from a slightly disordered pattern that exaggerates the alterations seen in the late proliferative phase of the menstrual cycle to irregular, hyperchromatic lesions that are similar to endometrioid adenocarcinoma. Generally, EH is caused by continuous exposure of estrogen unopposed by progesterone, polycystic ovary syndrome, tamoxifen, or hormone replacement therapy. Since it can progress, or often occur coincidentally with endometrial carcinoma, EH is of clinical importance, and the reversion of hyperplasia to normal endometrium represents the key conservative treatment for prevention of the development of adenocarcinoma. Presently, cyclic progestin or hysterectomy constitutes the major treatment option for EH without or with atypia, respectively. However, clinical trials of hormonal therapies and definitive standard treatments remain to be established for the management of EH. Moreover, therapeutic options for EH patients who wish to preserve fertility are challenging and require nonsurgical management. Therefore, future studies should focus on evaluation of new treatment strategies and novel compounds that could simultaneously target pathways involved in the pathogenesis of estradiol-induced EH. Novel therapeutic agents precisely targeting the inhibition of estrogen receptor, growth factor receptors, and signal transduction pathways are likely to constitute an optimal approach for treatment of EH. PMID:26463434

  15. Detection of and screening for endometrial cancer.

    PubMed

    Jaber, R

    1988-01-01

    Endometrial cancer occurs more than twice as frequently as cervical cancer. The main risk factors are age, estrogen use, and obesity. Increasing life expectancy and more liberal use of estrogen to prevent postmenopausal bone loss will probably increase the magnitude of the problem. Endometrial cancer is a heterogeneous disease. Good prognosis is associated with obesity and estrogen use and with carcinomas preceded by precancerous hyperplasia. A bad prognosis may be found in women without major risk factors and is associated with a normal or atrophic endometrium. Because of a high prevalence of asymptomatic disease (6.9 per 1,000) and because the group with a poor prognosis is usually asymptomatic, all postmenopausal women should be screened at least one time. For screening, the use of one of the cytologic instruments is recommended; these instruments are safe, easy to handle, and can be used in the office setting without anesthesia. Yields are comparable to dilation and curettage. Family physicians are encouraged to familiarize themselves with cytologic instruments and to use them for screening postmenopausal women in their office.

  16. Dilatation and Curettage Effect on the Endometrial Thickness

    PubMed Central

    Davar, Robab; Dehghani Firouzabadi, Razieh; Chaman Ara, Kefayat

    2013-01-01

    Background Endometrial receptivity is required for successful implantation and pregnancy. Despite the remaining controversy, many studies have shown that ultrasonographic endometrial thickness can be considered as an indicator of endometrial receptivity. Objective The study objective was to investigate the effect of dilatation and curettage on the endometrial thickness. Materials and Methods Enrolled in the study were 444 patients visited in Obstetrics & Gynecology clinic of Shahid Sadoughi hospital between Jan. 2011 to Sep. 2012. Only patients whose menstrual cycle was regular were included in study. Patients with myoma, adenomyosis, endometrial polyps or other uterine anomaly, those who smoked, whose BMI was greater than 30 and who were taking medications that could affect endometrial thickness were excluded. Endometrial thickness was measured one day before evolution (n = 444) and 5-7 days after it (n = 444) using transvaginal ultrasonography. The endometrial thicknesses were correlated to the patients’ history of dilatation and curettage. Data analysis was done through SPSS software version 16 and using descriptive statistics, independent T-test and Anova. Results Endometrial thickness in patients who had 0, 1, 2, 3 and 4 D&C were 10.00 ± 0.58, 9.83 ± 0.47, 8.90 ± 0.92, 7.42 ± 0.18 and 7.40 ± 0.07, respectively one day before ovulation (spearman’s correlation coefficient = -0.33) and 10.62 ± 0.68, 9.64 ± 0.49, 8.48 ± 0.96, 6.32 ± 0.15 and 6.90 ± 0.04, respectively, 5-7 days after ovulation (spearman’s correlation coefficient = -0.66) estradiol and progesterone levels, measured in the day of 2nd ultrasonography had not statistic relation with endometrial thickness (P = 0.27 and 0.31). The relation of endometrial thickness and age was not significant (P = 0.54 and 0.06). Conclusions Dilatation and curettage has a significant effect on the endometrial thinning. PMID:24083012

  17. Endometrial biopsy interpretation. Shortcomings and problems in current gynecologic practice.

    PubMed

    Van Bogaert, L J; Maldague, P; Staquet, J P

    1978-01-01

    The analysis of 345 endometrial biopsies was carried out with special regard to the relation between pathologic findings and presenting symptoms or complaints. Only 52.4% of the biopsies showed microscopic features possibly related to the complaints. Endometrial polyps and chronic endometritis were diagnosed in 21.1 and 9.8%, respectively, of the entire study group. The currently accepted definitions of dysfunctional uterine bleeding raise the question whether endometrial polyps and atypical secretory changes may or may not be included in the syndrome.

  18. Management options and fertility-preserving therapy for premenopausal endometrial hyperplasia and early-stage endometrial cancer.

    PubMed

    Gressel, Gregory M; Parkash, Vinita; Pal, Lubna

    2015-12-01

    Definitive management with hysterectomy could be appropriate for some patients with endometrial cancer and its precursor lesions, but poses challenges for those desiring future fertility. To review risk factors for endometrial hyperplasia/cancer among premenopausal women and discuss management options for fertility preservation. A literature search through the PubMed, Ovid, and Cochrane databases was conducted using the terms "endometrial hyperplasia" and "endometrial cancer," cross-referenced with "fertility preservation." All articles published in English between January 1, 2000, and January 1, 2015, were considered if they were readily available online. Articles were analyzed and information was synthesized into a comprehensive review. Chronic anovulation, obesity, polycystic ovarian syndrome, metabolic syndrome, insulin resistance, and type 2 diabetes mellitus must be appreciated as risk factors for endometrial pathology. Providers must exert vigilance in identifying patients at risk and in initiating pre-emptive strategies. Risk reduction with lifestyle modification, weight loss, and glycemic control can improve regression and overall health. Fertility outcomes for these patients are promising, especially with assisted reproductive technology. Conservative management could be appropriate for carefully selected women with complex atypical endometrial hyperplasia or early-stage endometrial cancer who desire future fertility. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Endometrial stem/progenitor cells: the first 10 years

    PubMed Central

    Gargett, Caroline E.; Schwab, Kjiana E.; Deane, James A.

    2016-01-01

    BACKGROUND The existence of stem/progenitor cells in the endometrium was postulated many years ago, but the first functional evidence was only published in 2004. The identification of rare epithelial and stromal populations of clonogenic cells in human endometrium has opened an active area of research on endometrial stem/progenitor cells in the subsequent 10 years. METHODS The published literature was searched using the PubMed database with the search terms ‘endometrial stem cells and menstrual blood stem cells' until December 2014. RESULTS Endometrial epithelial stem/progenitor cells have been identified as clonogenic cells in human and as label-retaining or CD44+ cells in mouse endometrium, but their characterization has been modest. In contrast, endometrial mesenchymal stem/stromal cells (MSCs) have been well characterized and show similar properties to bone marrow MSCs. Specific markers for their enrichment have been identified, CD146+PDGFRβ+ (platelet-derived growth factor receptor beta) and SUSD2+ (sushi domain containing-2), which detected their perivascular location and likely pericyte identity in endometrial basalis and functionalis vessels. Transcriptomics and secretomics of SUSD2+ cells confirm their perivascular phenotype. Stromal fibroblasts cultured from endometrial tissue or menstrual blood also have some MSC characteristics and demonstrate broad multilineage differentiation potential for mesodermal, endodermal and ectodermal lineages, indicating their plasticity. Side population (SP) cells are a mixed population, although predominantly vascular cells, which exhibit adult stem cell properties, including tissue reconstitution. There is some evidence that bone marrow cells contribute a small population of endometrial epithelial and stromal cells. The discovery of specific markers for endometrial stem/progenitor cells has enabled the examination of their role in endometrial proliferative disorders, including endometriosis, adenomyosis and Asherman

  20. Endometrial stem/progenitor cells: the first 10 years.

    PubMed

    Gargett, Caroline E; Schwab, Kjiana E; Deane, James A

    2016-01-01

    The existence of stem/progenitor cells in the endometrium was postulated many years ago, but the first functional evidence was only published in 2004. The identification of rare epithelial and stromal populations of clonogenic cells in human endometrium has opened an active area of research on endometrial stem/progenitor cells in the subsequent 10 years. The published literature was searched using the PubMed database with the search terms 'endometrial stem cells and menstrual blood stem cells' until December 2014. Endometrial epithelial stem/progenitor cells have been identified as clonogenic cells in human and as label-retaining or CD44(+) cells in mouse endometrium, but their characterization has been modest. In contrast, endometrial mesenchymal stem/stromal cells (MSCs) have been well characterized and show similar properties to bone marrow MSCs. Specific markers for their enrichment have been identified, CD146(+)PDGFRβ(+) (platelet-derived growth factor receptor beta) and SUSD2(+) (sushi domain containing-2), which detected their perivascular location and likely pericyte identity in endometrial basalis and functionalis vessels. Transcriptomics and secretomics of SUSD2(+) cells confirm their perivascular phenotype. Stromal fibroblasts cultured from endometrial tissue or menstrual blood also have some MSC characteristics and demonstrate broad multilineage differentiation potential for mesodermal, endodermal and ectodermal lineages, indicating their plasticity. Side population (SP) cells are a mixed population, although predominantly vascular cells, which exhibit adult stem cell properties, including tissue reconstitution. There is some evidence that bone marrow cells contribute a small population of endometrial epithelial and stromal cells. The discovery of specific markers for endometrial stem/progenitor cells has enabled the examination of their role in endometrial proliferative disorders, including endometriosis, adenomyosis and Asherman's syndrome

  1. Adenovirus mediated homozygous endometrial epithelial Pten deletion results in aggressive endometrial carcinoma

    SciTech Connect

    Joshi, Ayesha; Ellenson, Lora Hedrick

    2011-07-01

    Pten is the most frequently mutated gene in uterine endometriod carcinoma (UEC) and its precursor complex atypical hyperplasia (CAH). Because the mutation frequency is similar in CAH and UEC, Pten mutations are thought to occur relatively early in endometrial tumorigenesis. Previous work from our laboratory using the Pten{sup +/-} mouse model has demonstrated somatic inactivation of the wild type allele of Pten in both CAH and UEC. In the present study, we injected adenoviruses expressing Cre into the uterine lumen of adult Pten floxed mice in an attempt to somatically delete both alleles of Pten specifically in the endometrium. Our results demonstrate that biallelic inactivation of Pten results in an increased incidence of carcinoma as compared to the Pten{sup +/-} mouse model. In addition, the carcinomas were more aggressive with extension beyond the uterus into adjacent tissues and were associated with decreased expression of nuclear ER{alpha} as compared to associated CAH. Primary cultures of epithelial and stromal cells were prepared from uteri of Pten floxed mice and Pten was deleted in vitro using Cre expressing adenovirus. Pten deletion was evident in both the epithelial and stromal cells and the treatment of the primary cultures with estrogen had different effects on Akt activation as well as Cyclin D3 expression in the two purified components. This study demonstrates that somatic biallelic inactivation of Pten in endometrial epithelium in vivo results in an increased incidence and aggressiveness of endometrial carcinoma compared to mice carrying a germline deletion of one allele and provides an important in vivo and in vitro model system for understanding the genetic underpinnings of endometrial carcinoma.

  2. Epidemiology of Endometrial Cancer Consortium (E2C2)

    Cancer.gov

    The Epidemiology of Endometrial Cancer Consortium studies the etiology of this common cancer and build on resources from existing studies by combining data across studies in order to advance the understanding of the etiology of this disease.

  3. miR-200 Regulates Endometrial Development During Early Pregnancy.

    PubMed

    Jimenez, Patricia T; Mainigi, Monica A; Word, R Ann; Kraus, W Lee; Mendelson, Carole R

    2016-09-01

    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.

  4. Endometrial Adenocarcinoma in a 27-Year-Old Woman

    PubMed Central

    Fadhlaoui, Anis; Ben Hassouna, Jamel; Khrouf, Mohamed; Zhioua, Fethi; Chaker, Anis

    2010-01-01

    Background Endometrial adenocarcinoma usually occurs after menopause, but in 2%–14% of cases, it occurs in young patients (less than 40 years of age) who are eager to preserve their fertility. Its treatment includes hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy, and, in some cases, radiation therapy. Aim To describe a case of endometrial adenocarcinoma occurring in a young woman and to undertake a literature review of risk factors and therapeutic options proposed for young women wishing to preserve their fertility. Case We report a case of endometrial cancer in a 27-year-old woman treated for resistant menorrhagia and cared for in our department as well as in the Salah Azaiez Institute. Conclusion Endometrial adenocarcinoma rarely occurs in young women. In such cases, other therapeutic options can be proposed: progesterone therapy and LH-RH (Luteinzing-Hormone-Releasing-Hormone) agonists therapy in order to preserve fertility in younger patients. PMID:21769252

  5. Endometrial and acute myeloid leukemia cancer genomes characterized

    Cancer.gov

    Two studies from The Cancer Genome Atlas (TCGA) program reveal details about the genomic landscapes of acute myeloid leukemia (AML) and endometrial cancer. Both provide new insights into the molecular underpinnings of these cancers.

  6. New use of microsatellite instability analysis in endometrial cancer.

    PubMed

    Kunitomi, Haruko; Banno, Kouji; Yanokura, Megumi; Takeda, Takashi; Iijima, Moito; Nakamura, Kanako; Iida, Miho; Adachi, Masataka; Watanabe, Keiko; Matoba, Yusuke; Kobayashi, Yusuke; Tominaga, Eiichiro; Aoki, Daisuke

    2017-09-01

    The increasing incidence of obesity and diabetes due to changes in diet, earlier menarche, delayed menopause, late marriage, and declining birth rate have resulted in an increase in the number of endometrial cancer cases over the last few decades. Although surgical therapy is sufficient for early endometrial cancer, there is no effective therapy for patients with advanced and recurrent endometrial cancer. The oncogenic mechanism of endometrial cancer involves microsatellite instability (MSI) caused by dysfunction of DNA mismatch repair genes in 30% of patients. Immune checkpoint inhibitors, including anti-programmed death (PD)-1 and anti-PD-ligand 1 antibodies, are of interest as novel anticancer drugs; however, these drugs are currently expensive, and there is a need to select patients who will benefit from their use. The use of MSI analysis as a predictive biomarker for the therapeutic efficacy of these drugs may be useful for reducing the costs of drug therapy.

  7. [ENDOMETRIAL POLYPS--CLINICOPATHOLOGICAL FEATURES OF MALIGNANCY AND THERAPEUTIC ATTITUDE].

    PubMed

    Yamakov, K

    2016-01-01

    Endometrial polyps represent a localized overgrowth of the endometrium, projecting above the epithelium. Endometrialpolyps maybe single or multiple, may measure from a few millimeters to centimeters, and maybe sessile or pedunculated. The use of transvaginal ultrasound is inevitably entailing a significant increase in the number of women diagnosed with endometrial polyps. Endometrial polyps are usually benign although some may be precancerous or cancerous. The prevalence of malignant change in EMPs varies from 0.8 to 8%. Hysteroscopic polypectomy is effective and safe as both a diagnostic and therapeutic intervention. It remains the gold standard for treatment. Given that most polyps are not malignant, there is an option for expectant management with no intervention. It is impotant to evaluate the prevalence of endometrial premalignant and malignant polyps in premenopausal and postmenopausal women, as well as the clinical, ultrasound, and hysteroscopic factors associated with malignancy. Asymptomatic postmenopausal polyps are unlikely to be malignant and observation is an option after discussion with the patient.

  8. [Current possibilities of examination and preservative treatment in endometrial hyperplasia].

    PubMed

    Kołodziejczak, Małgorzata; Knapp, Paweł; Kuźmicki, Mariusz; Knapp, Piotr

    2011-07-01

    Endometrial hyperplasia is one of the most frequent reasons of pre- and menopausal bleeding. In recent years, knowledge of biology of hyperplastic endometrium has changed some medical guidelines in a group of patients diagnosed with endometrial lesions. In many cases radical procedures have been replaced with preservative treatment, especially for those women who wished to spare their uterus. Also, in many high-risk surgical procedures there are a number of algorithms which allow to perform non-radical treatment in those cases. Enforcement of those strategy should be linked to precise examination of endometrium morphology Summarizing, a preservative treatment in case of endometrial hyperplasia needs sensitive and specific tests which determine safety limits of the procedure. This paper has presented current possibilities of examination and non-radical treatment of endometrial hyperplasia.

  9. Stromal-to-Epithelial Transition during Postpartum Endometrial Regeneration

    PubMed Central

    Huang, Cheng-Chiu; Orvis, Grant D.; Wang, Ying; Behringer, Richard R.

    2012-01-01

    Endometrium is the inner lining of the uterus which is composed of epithelial and stromal tissue compartments enclosed by the two smooth muscle layers of the myometrium. In women, much of the endometrium is shed and regenerated each month during the menstrual cycle. Endometrial regeneration also occurs after parturition. The cellular mechanisms that regulate endometrial regeneration are still poorly understood. Using genetic fate-mapping in the mouse, we found that the epithelial compartment of the endometrium maintains its epithelial identity during the estrous cycle and postpartum regeneration. However, whereas the stromal compartment maintains its identity during homeostatic cycling, after parturition a subset of stromal cells differentiates into epithelium that is subsequently maintained. These findings identify potential progenitor cells within the endometrial stromal compartment that produce long-term epithelial tissue during postpartum endometrial regeneration. PMID:22970108

  10. Dicer1 dysfunction promotes stemness and aggression in endometrial carcinoma.

    PubMed

    Wang, Xiao-Jun; Jiang, Fei-Zhou; Tong, Huan; Ke, Jie-Qi; Li, Yi-Ran; Zhang, Hui-Lin; Yan, Xiao-Fang; Wang, Fang-Yuan; Wan, Xiao-Ping

    2017-04-01

    Endometrial carcinoma is one of the most common gynecological malignancies, but the molecular events involved in the development and progression of endometrial carcinoma remain unclear. Dicer1 and cancer stem cells play important roles in cell motility and survival. This study investigated the role of the let-7 family and Dicer1 in the stemness of endometrial carcinoma cells. We profiled Dicer1 expression in clinical samples and explored its relationship with stem cell-associated markers and clinical parameters. We showed that Dicer1 dysfunction leads to the enrichment of tumor stemness features and tumor aggression both in vitro and in vivo. We also identified the mechanism related to this potential tumor-predisposing phenotype: loss of Dicer1 induced abnormal expression of the let-7 family, which comprises well-known tumor suppressors, thus regulating stemness in endometrial carcinoma cells.

  11. DNA Methylation Machinery in the Endometrium and Endometrial Cancer.

    PubMed

    Caplakova, Veronika; Babusikova, Eva; Blahovcova, Eva; Balharek, Tomas; Zelieskova, Maria; Hatok, Jozef

    2016-09-01

    During the normal menstrual cycle, endometrial tissue undergoes many biochemical and morphological changes which are under the control of steroid hormone levels. DNA methylation plays a key role in gene expression regulation and influences functional changes in endometrial tissue. Eliminating senescent cells from the functional layer of the endometrium is mediated by apoptotic cell death, which helps maintain cellular homeostasis. Aberrant DNA methylation changes result in deregulation of important apoptotic proteins during endometrial carcinogenesis and thus apoptosis resistance development. Evading apoptosis is still a major problem in the successful treatment of endometrial cancer patients with advanced disease. Despite intensive study of the cancer epigenome, there is missing information about disrupted apoptotic gene regulation in DNA methylation levels. Therefore, it is necessary to spread our knowledge in the field of epigenetics to help us differentiate normal and cancer tissues and detect the early stages of cancer disease. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. Endometrial carcinoma metastatic to the clitoris: a case report and review of the literature.

    PubMed

    Fakor, Fereshteh; Hajizadeh Falah, Hadi; Khajeh Jahromi, Sina

    2013-01-01

    Endometrial cancer generally carries a good prognosis. Endometrial carcinoma more frequently metastasizes to the pelvic and para-aortic nodes. Visceral metastases usually occur in the vagina and ovaries. Distant metastases involve lungs and occur as a terminal event. This case report describes vulvalar metastasis of endometrial cancer to the clitoris. Metastatic tumors of the vulva are rare. Moreover, in the presence of metastatic endometrial carcinoma to the vulva, it is necessary to verify if other visceral metastases are present. Endometrial cancer can extend through direct dermatogens and lymphatic spread. We report a clitoral metastasis of an endometrial carcinoma and discuss whether the possible mechanism is vascular spreading or direct seeding.

  13. Survival outcome in endometrial cancer patients according to hereditary predisposition.

    PubMed

    Yoo, Heon Jong; Lim, Myong Cheol; Son, Yedong; Seo, Sang-Soo; Kang, Sokbom; Kim, Sun Ho; Yoo, Chong Woo; Park, Sang-Yoon

    2015-02-01

    A familial history of ovarian cancer/breast cancer is considered a significant prognostic factor for ovarian cancer. We investigated hereditary factors by examining the incidence of synchronous malignancy in patients with endometrial cancer, and assessed the prognostic role of heredity in endometrial cancer. We retrospectively evaluated patients with endometrial cancer who underwent surgery from January 2001 to April 2011. A hereditary background in this study was defined as double primary cancer, that is, endometrial cancer accompanied by colon, ovarian, or breast cancer suggestive of Lynch syndrome, hereditary breast ovarian cancer syndrome, or Cowden syndrome, respectively. Among 282 patients with endometrial cancer in the study population, 20 patients (7.1%) had a hereditary predisposition: 10 patients (3.5%) had ovarian cancer, six patients (2.1%) had breast cancer, and four patients (1.4%) had colon cancer. Age and lower uterine segment involvement were not statistically different between the hereditary and nonhereditary groups. The majority of the women in the hereditary group presented with Stage I cancer; however, there were no significant differences in Stage I cancer between the hereditary group and the sporadic endometrial cancer group (85% and 77%, respectively, p = 0.561). The median follow-up period was 60 months. A 5-year overall survival rate was not different between the two groups (95% and 95%, respectively, p = 0.659). Among a subgroup of patients with Stage I endometrial cancer, the 5-year overall survival rate was lower in the endometrial cancer with a hereditary predisposition group compared with the sporadic endometrial cancer group (94% and 98%, respectively, p = 0.027). Seven percent of the women with endometrial cancer in our study had other malignancies such as ovarian, colon, or breast cancer synchronously. Among a subgroup of patients with Stage I cancer in the endometrial cancer with a hereditary predisposition group, the 5-year

  14. Levonorgestrel-releasing intrauterine system for atypical endometrial hyperplasia.

    PubMed

    Luo, Li; Luo, Bing; Zheng, Ying; Zhang, Heng; Li, Jing; Sidell, Neil

    2013-06-05

    Endometrial carcinoma is the most common gynaecologic malignancy in the world and develops through preliminary stages of endometrial hyperplasia. Typical endometrial hyperplasia suggests a significant pre-malignant state with frank progression to endometrial carcinoma. Because atypical endometrial hyperplasia tends to occur at a young age, it has become increasingly important and necessary to find a safe and effective fertility-sparing treatment with better tolerability and fewer side effects than the options for treatment that are currently available. The levonorgestrel-releasing intrauterine system has already been used to provide endometrial protection in women with breast cancer who are on adjuvant tamoxifen. The antiproliferative function of levonorgestrel is thought to reduce the risk of endometrial hyperplasia. To determine the efficacy and safety of the levonorgestrel-releasing intrauterine system in reversing atypical endometrial hyperplasia. In November 2012 we searched the Cochrane Menstrual Disorders and Subfertility Review Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library; MEDLINE; EMBASE; and the China National Knowledge Infrastructure for relevant trials. Attempts were made to identify trials from references in published studies. We also searched for ongoing trials in five major clinical trials registries. Randomised controlled trials (RCTs) of the levonorgestrel-releasing intrauterine system (LNG-IUS) versus progestin therapy in women with a confirmed histological diagnosis of simple or complex endometrial hyperplasia with atypia. No eligible study was found. We did not identify any studies which met our full inclusion criteria. There is no evidence available from randomised controlled trials regarding the efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) for atypical endometrial hyperplasia. RCTS are

  15. Factors Influencing Endometrial Thickness in Postmenopausal Women

    PubMed Central

    Hebbar, S; Chaya, V; Rai, L; Ramachandran, A

    2014-01-01

    Background: Cut-off values for endometrial thickness (ET) in asymptomatic postmenopausal woman have been standardized. However, there are no comprehensive studies to document how various factors can influence the ET after the age of menopause. Aim: To study the various factors influencing the ET in postmenopausal women. Subjects and Methods: This was a prospective observational study. A total of 110 postmenopausal women underwent detailed history taking, clinical examination, and transvaginal scan for uterine volume and ovarian volume. The volumes were calculated by using ellipsoid formula: Width × thickness × height × 0.523. The variation in ET with respect to the influencing factors such as age, duration of menopause, parity, body mass index (BMI), medical illness like diabetes/hypertension, drugs like tamoxifen, presence of myoma, uterine volume, ovarian volume, and serum estradiol (in selected patients) were measured. Descriptive analysis was performed using SPSS software (version 16, Chicago II, USA) to obtain mean, standard deviation (SD), 95% confidence intervals (CIs) and inter quartile ranges. Comparison of means was carried out using analysis of variance. Results: The mean (SD) age of the patients was 55.4 (6.91) years (95% CI, 54.1, 56.7). The mean (SD) age at menopause was 47.95 (3.90) years (95% CI, 47.2, 48.7) and the mean (SD) duration of menopause was 7.27 (6.65) years (95% CI, 6.01, 8.53). The mean (SD) ET was 3.8 (2.3) mm (95% CI, 3.36, 4.23). Medical illness like diabetes and hypertension did not alter the ET. ET increased as BMI increased and it was statistically significant. The presence of myoma increased uterine volume significantly and was associated with thick endometrial stripe. Similarly, whenever the ovaries were visualized and as the ovarian volume increased, there was an increase in ET. When ET was > 4 mm (n = 37), they were offered endocel, of which 16 agreed to undergo the procedure. None were found to have endometrial cancer

  16. 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.

  17. Endometrial glands are required for preimplantation conceptus elongation and survival.

    PubMed

    Gray, C A; Taylor, K M; Ramsey, W S; Hill, J R; Bazer, F W; Bartol, F F; Spencer, T E

    2001-06-01

    Endometrial glands secrete molecules hypothesized to support conceptus growth and development. In sheep, endometrial gland morphogenesis occurs postnatally and can be epigenetically ablated by neonatal progestin exposure. The resulting stable adult uterine gland knockout (UGKO) phenotype was used here to test the hypothesis that endometrial glands are required for successful pregnancy. Mature UGKO ewes were bred repeatedly to fertile rams, but no pregnancies were detected by ultrasound on Day 25. Day 7 blastocysts from normal superovulated ewes were then transferred synchronously into Day 7 control or UGKO ewes. Ultrasonography on Days 25-65 postmating indicated that pregnancy was established in control, but not in UGKO ewes. To examine early uterine-embryo interactions, four control and eight UGKO ewes were bred to fertile rams. On Day 14, their uteri were flushed. The uterus of each control ewe contained two filamentous conceptuses of normal length. Uteri from four UGKO ewes contained no conceptus. Uteri of three UGKO ewes contained a single severely growth-retarded tubular conceptus, whereas the remaining ewe contained a single filamentous conceptus. Histological analyses of these uteri revealed that endometrial gland density was directly related to conceptus survival and developmental state. Day 14 UGKO uteri that were devoid of endometrial glands did not support normal conceptus development and contained either no conceptuses or growth-retarded tubular conceptuses. The Day 14 UGKO uterus with moderate gland development contained a filamentous conceptus. Collectively, these results demonstrate that endometrial glands and, by inference, their secretions are required for periimplantation conceptus survival and development.

  18. Persistence of endometrial activity after radiation therapy for cervical carcinoma

    SciTech Connect

    Barnhill, D.; Heller, P.; Dames, J.; Hoskins, W.; Gallup, D.; Park, R.

    1985-12-01

    Radiation therapy is a proved treatment for cervical carcinoma; however, it destroys ovarian function and has been thought to ablate the endometrium. Estrogen replacement therapy is often prescribed for patients with cervical carcinoma after radiation therapy. A review of records of six teaching hospitals revealed 16 patients who had endometrial sampling for uterine bleeding after standard radiation therapy for cervical carcinoma. Fifteen patients underwent dilatation and curettage, and one patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy when a dilatation and curettage was unsuccessful. Six patients had fibrosis and inflammation of the endometrial cavity, seven had proliferative endometrium, one had cystic hyperplasia, one had atypical adenomatous hyperplasia, and one had adenocarcinoma. Although the number of patients who have an active endometrium after radiation therapy for cervical carcinoma is not known, this report demonstrates that proliferative endometrium may persist, and these patients may develop endometrial hyperplasia or adenocarcinoma. Studies have indicated that patients with normal endometrial glands have an increased risk of developing endometrial adenocarcinoma if they are treated with unopposed estrogen. Patients who have had radiation therapy for cervical carcinoma should be treated with estrogen and a progestational agent to avoid endometrial stimulation from unopposed estrogen therapy.

  19. Hormone therapy for younger patients with endometrial cancer.

    PubMed

    Lee, Wen-Ling; Lee, Fa-Kung; Su, Wen-Hsiang; Tsui, Kuan-Hao; Kuo, Cheng-Deng; Hsieh, Shie-Liang Edmond; Wang, Peng-Hui

    2012-12-01

    The relationship between hormones and endometrial cancer is well known because disease states, such as chronic anovulation and endogenous estrogen production from hormone-secreting tumors (for example, granulosa cell tumor of the ovary), are related to excess estrogen, and unopposed estrogen use might lead to endometrial overgrowth, hyperplasia, and subsequent development of endometrial carcinoma. Therefore, the possibility of using antihormone therapy in endometrial carcinoma and/or its precancer lesions, such as simple hyperplasia with and without atypia and complex hyperplasia with and without atypia, is always supposed, as in the management of breast cancer. In addition, if women in whom endometrial cancer is diagnosed are very young, some critical issues should be considered, including the possibility of ovary preservation-partial preservation of fertility and the possibility of both ovary and uterus preservation-complete preservation of fertility. Other factors are also important to consider and include oncologic risk, appropriateness of candidates for treatment, type of hormone use, response rate of hormonal therapy, appropriate surveillance, and additional counseling for issues such as anxiety about relapse and metastasis, distress about side effects, advice of the family, advice of the medical staff, and economic burden. This review will be focused on updated information and recent knowledge of the use of hormones in the management of younger women with endometrial cancer who want fertility preservation.

  20. Norethindrone acetate and estradiol-induced endometrial hyperplasia.

    PubMed

    Kurman, R J; Félix, J C; Archer, D F; Nanavati, N; Arce, J; Moyer, D L

    2000-09-01

    To identify the lowest effective continuous dose of norethindrone acetate that significantly reduces 12-month incidence of endometrial hyperplasia associated with unopposed 17beta-estradiol (E2), 1 mg. In a double-masked, randomized, multicenter study, 1176 healthy postmenopausal women 45 years of age or older without evidence of endometrial abnormalities were given 12 months of treatment with unopposed E2, 1 mg, or continuous-combined regimens of E2, 1 mg, and norethindrone acetate, 0.1 mg, 0.25 mg, or 0.5 mg. Endometrial histology was evaluated at the end of the treatment period. Continuous-combined E2-norethindrone acetate regimens significantly reduced 12-month incidence of endometrial hyperplasia compared with unopposed E2 1 mg (P <.001). Endometrial hyperplasia occurred in 14.6% of women treated with unopposed E2 1 mg, whereas in all continuous-combined groups, the rate decreased to less than 1%. Among patients who received E2-norethindrone acetate 0.1 mg, incidence was 0.8%; among those who received 0.25 mg and 0.5 mg, it was 0.4%. Continuous norethindrone acetate at doses as low as 0.1 mg combined with E2 1 mg effectively negated risk for endometrial hyperplasia associated with unopposed E2 1 mg, at least for the first year of therapy.

  1. Dosimetry for photodynamic therapy of endometrial tissue

    NASA Astrophysics Data System (ADS)

    Svaasand, Lars O.; Fehr, Mathias K.; Madsen, Sten; Tadir, Yona; Tromberg, Bruce J.

    1995-05-01

    Hysterectomy is the most common major operation performed in the United States with dysfunctional uterine bleeding as one of the major indications. The clinical needs for simple and safe endometrial destruction are essential. Photodynamic therapy (PDT) may offer a simple and cost effective solution for the treatment of dysfunctional uterine bleeding. The dosimetry is discussed for the case of topical application of photosensitizer. This technique might be the method of preference because undesired side effects such as skin photosensitization that is typical for systemically injected photosensitizers, can be avoided. Effective PDT requires a sufficient amount of light delivered to the targeted tissue in a reasonable period of time. A trifurcated optical applicator consisting of three cylindrical diffusing fibers has been constructed, and this applicator can deliver a typical required optical dose of about 50-100 J/cm2 to the full depth of the endometrium for an exposure time of 10-20 minutes.

  2. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    PubMed Central

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  3. [Modern therapy concepts for endometrial cancer].

    PubMed

    Emons, G; Hellriegel, M; Hawighorst, T

    2009-07-01

    Most cases of endometrial cancer (EC) become symptomatic at an early stage and have a good prognosis. EC has been traditionally treated with total abdominal hysterectomy plus bilateral salpingo-oophorectomy. For early stage, low grade cases (endometrioid, pT1a, pT1b; G1, G2) this is adequate therapy. For higher stages and grades, especially for type II EC (serous, clear cell) this therapy is insufficient. The efficacy of systematic pelvic and paraaortic lymphadenectomy for high risk EC, however, remains to be evaluated. External pelvic radiotherapy has been shown to improve local control in stage I and II EC, but has no positive effect on survival. A comparable improvement of local control can be achieved by vaginal brachytherapy with significantly less toxicity. Adjuvant chemotherapy is probably efficacious in EC. Its usefulness as exclusive adjuvant therapy or in combination with brachytherapy and/or external beam therapy remains to be evaluated by prospective trials.

  4. Comparison of diagnostic accuracy between endometrial curettage and pipelle aspiration biopsy in patients treated with progestin for endometrial hyperplasia: a Korean Gynecologic Oncology Group Study (KGOG 2019).

    PubMed

    Kim, Mi Kyoung; Seong, Seok Ju; Lee, Taek Sang; Ki, Kyung-Do; Lim, Myong Cheol; Kim, Yun Hwan; Kim, Kidong; Joo, Won Duk

    2015-10-01

    A prospective multicenter trial has been started in Korea to evaluate the diagnostic accuracy of endometrial aspiration biopsy compared with dilatation and curettage in patients treated with progestin for endometrial hyperplasia. For conservative treatment of endometrial hyperplasia, orally administered progestins are most commonly used method with various treatment regimens and more recently, the levonorgestrel-releasing intrauterine system also has been used successfully to treat endometrial hyperplasia. However, there is no report about the accuracy of endometrial sampling during hormonal treatment for follow-up evaluation of endometrial hyperplasia. Patients with histologically confirmed endometrial hyperplasia are offered hormonal treatment with any one of the following three options: oral medroxyprogesterone acetate 10 mg/day for 14 days per cycle, continuous oral medroxyprogesterone acetate 10 mg/day or insertion of levonorgestrel-releasing intrauterine system. Histological surveillance is performed at 3 months or 6 months following initial treatment. Endometrial tissues are obtained via endometrial aspiration biopsy using a pipelle and dilatation and curettage. In the case of levonorgestrel-releasing intrauterine system, endometrial aspiration biopsy will be done with levonorgestrel-releasing intrauterine system in uterus and then, after the removal of levonorgestrel-releasing intrauterine system, dilatation and curettage will be done. The biopsy findings will be compared. The primary endpoint is to compare the pathological outcome of endometrial aspiration with dilatation and curettage. The secondary endpoint is the response rate with three types of progestin treatment at 6 months.

  5. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in patients with endometrial hyperplasia and endometrial cancer.

    PubMed

    Ural, Ülkü Mete; Şehitoğlu, İbrahim; Tekin, Yeşim Bayoğlu; Şahin, Figen Kir

    2015-03-01

    Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and platelet distribution width (PDW) may indicate the systemic inflammatory response associated with various cancers. We aimed to investigate the relationship between NLR, PLR, PDW and endometrial pathologies including hyperplasia and cancer. In this study, 472 cases who underwent endometrial biopsy were included. Three groups were constituted with respect to biopsy results: group 1, endometrial cancer patients (n = 54); group 2, endometrial hyperplasia patients (n = 152); and group 3, patients with normal biopsy results (n = 281). White blood cell and platelet counts as well as NLR, PLR and PDW recorded from complete blood counts obtained on the same day of biopsy were compared in the three groups. Endometrial cancer patients were significantly older than the cases in the other two groups (P < 0.001). The NLR in group 1 was significantly higher than group 3 (P = 0.02). However, there was no difference between the three groups with respect to PLR (P = 0.167). PDW was increased in group 1 compared to group 3 (P < 0.001). Results of our study have shown that NLR, PLR and PDW are simple, readily available and robust inflammatory markers that may be used in the management of endometrial pathologies. However, the actual predictive potential of these biomarkers still warrants further trials. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  6. PIK3R1 (p85α) is somatically mutated at high frequency in primary endometrial cancer.

    PubMed

    Urick, Mary E; Rudd, Meghan L; Godwin, Andrew K; Sgroi, Dennis; Merino, Maria; Bell, Daphne W

    2011-06-15

    Phosphoinositide 3-kinase (PI3K) is an important therapeutic target. Mutations in PIK3CA, which encodes p110α, the catalytic subunit of PI3K, occur in endometrioid endometrial cancers (EEC) and nonendometrioid endometrial cancers (NEEC). The goal of this study was to determine whether PIK3R1, which encodes p85α, the inhibitory subunit of PI3K, is mutated in endometrial carcinoma. We carried out exonic sequencing of PIK3R1 from 42 EECs and 66 NEECs. The pattern of PIK3R1 mutations was compared with the patterns of PIK3CA, PTEN, and KRAS mutations. The biochemical effect of seven PIK3R1 mutations was examined by stable expression in U2OS cells, followed by coimmunoprecipitation analysis of p110α, and Western blotting of phospho-AKT(Ser473) (p-AKT(Ser473)). We found that PIK3R1 was somatically mutated in 43% of EECs and 12% of NEECs. The majority of mutations (93.3%) were localized to the p85α-nSH2 and -iSH2 domains. Several mutations were recurrent. PIK3R1 mutations were significantly (P = 0.0015) more frequent in PIK3CA-wild type EECs (70%) than in PIK3CA mutant EECs (18%). Introduction of wild-type p85α into U2OS cells reduced the level of p-AKT(Ser473) compared with the vector control. Five p85α mutants, p85αdelH450-E451, p85αdelK459, p85αdelY463-L466, p85αdelR574-T576, and the p85αN564D positive control, were shown to bind p110α and led to increased levels of p-AKT(Ser473). The p85αR348X and p85αK511VfsX2 mutants did not bind p110α and showed no appreciable change in p-AKT(Ser473) levels. In conclusion, our study has revealed a new mode of PI3K alteration in primary endometrial tumors and warrants future studies to determine whether PIK3R1 mutations correlate with clinical outcome to targeted therapies directed against the PI3K pathway in EEC and NEEC.

  7. Cancer-Associated Fibroblasts Promote Proliferation of Endometrial Cancer Cells

    PubMed Central

    Subramaniam, Kavita S.; Tham, Seng Tian; Mohamed, Zahurin; Woo, Yin Ling; Mat Adenan, Noor Azmi; Chung, Ivy

    2013-01-01

    Endometrial cancer is the most commonly diagnosed gynecologic malignancy worldwide; yet the tumor microenvironment, especially the fibroblast cells surrounding the cancer cells, is poorly understood. We established four primary cultures of fibroblasts from human endometrial cancer tissues (cancer-associated fibroblasts, CAFs) using antibody-conjugated magnetic bead isolation. These relatively homogenous fibroblast cultures expressed fibroblast markers (CD90, vimentin and alpha-smooth muscle actin) and hormonal (estrogen and progesterone) receptors. Conditioned media collected from CAFs induced a dose-dependent proliferation of both primary cultures and cell lines of endometrial cancer in vitro (175%) when compared to non-treated cells, in contrast to those from normal endometrial fibroblast cell line (51%) (P<0.0001). These effects were not observed in fibroblast culture derived from benign endometrial hyperplasia tissues, indicating the specificity of CAFs in affecting endometrial cancer cell proliferation. To determine the mechanism underlying the differential fibroblast effects, we compared the activation of PI3K/Akt and MAPK/Erk pathways in endometrial cancer cells following treatment with normal fibroblasts- and CAFs-conditioned media. Western blot analysis showed that the expression of both phosphorylated forms of Akt and Erk were significantly down-regulated in normal fibroblasts-treated cells, but were up-regulated/maintained in CAFs-treated cells. Treatment with specific inhibitors LY294002 and U0126 reversed the CAFs-mediated cell proliferation (P<0.0001), suggesting for a role of these pathways in modulating endometrial cancer cell proliferation. Rapamycin, which targets a downstream molecule in PI3K pathway (mTOR), also suppressed CAFs-induced cell proliferation by inducing apoptosis. Cytokine profiling analysis revealed that CAFs secrete higher levels of macrophage chemoattractant protein (MCP)-1, interleukin (IL)-6, IL-8, RANTES and vascular

  8. Absence of MGMT promoter methylation in endometrial cancer.

    PubMed

    Rimel, B J; Huettner, Phyllis; Powell, Matthew A; Mutch, David G; Goodfellow, Paul J

    2009-01-01

    O(6)-methylguanine-DNA methyltransferase (MGMT) acts to repair DNA damaged by alkylation of guanine residues. MGMT promoter methylation and gene silencing is seen in a variety of cancers and pre-cancerous changes [Ogino S, Meyerhardt JA, Kawasaki T, et al. CpG island methylation, response to combination chemotherapy, and patient survival in advanced microsatellite stable colorectal carcinoma. Virchows Arch 2007;450:529-37; Rodriguez MJ, Acha A, Ruesga MT, Rodriguez C, Rivera JM, Aguirre JM. Loss of expression of DNA repair enzyme MGMT in oral leukoplakia and early oral squamous cell carcinoma. A prognostic tool? Cancer Lett 2007;245:263-8; Ishii T, Murakami J, Notohara K, et al. Oesophageal squamous cell carcinoma may develop within a background of accumulating DNA methylation in normal and dysplastic mucosa. Gut 2007;56:13-9]. The loss of MGMT activity and promoter methylation is associated with increased sensitivity to alkylating agents and is a favorable prognostic indicator in gliomas [Weaver KD, Grossman SA, Herman JG. Methylated tumor-specific DNA as a plasma biomarker in patients with glioma. Cancer Invest 2006;24:35-40; Esteller M, Garcia-Foncillas J, Andion E, et al. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 2000;343:1350-4; Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005;352:997-1003]. We sought to determine if MGMT promoter methylation plays a role in endometrial cancer. One hundred and twenty primary endometrial cancers were analyzed for MGMT promoter methylation by combined bisulfite restriction analysis (COBRA). The cohort included 77 endometrioid endometrial cancers, 43 endometrial tumors of adverse histologic type, and 6 endometrial cancer cell lines. Twenty-one endometrioid and mixed endometrioid ovarian cancers were also analyzed. A subset of the primary tumors was analyzed for MGMT expression by

  9. Pre-operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding.

    PubMed

    Tan, Yu Hwee; Lethaby, Anne

    2013-11-15

    Heavy menstrual bleeding is one of the most common reasons for referral of premenopausal women to a gynaecologist. Although medical therapy is generally first line, many women eventually will require further treatment. Endometrial ablation by hysteroscopic and more recent "second-generation" devices such as balloon, radiofrequency or microwave ablation offers a day-case surgical alternative to hysterectomy. Complete endometrial destruction is one of the main determinants of treatment success. Surgery is most effective if undertaken when endometrial thickness is less than four millimeters. One option is to perform the surgery in the immediate postmenstrual phase, which is not always practical. The other option is to use hormonal agents that induce endometrial thinning pre-operatively. The most commonly evaluated agents are goserelin (a gonadotrophin-releasing hormone analogue, or GnRHa) and danazol. Other GnRH analogues and progestogens have also been studied, although fewer data are available. It has been suggested that these agents will reduce operating time, improve the intrauterine operating environment and reduce absorption of fluid used for intraoperative uterine cavity distension. They may also improve long-term outcomes, including menstrual loss and dysmenorrhoea. To investigate the effectiveness and safety of pre-operative endometrial thinning agents (GnRH agonists, danazol, estrogen-progestins and progestogens) versus another agent or placebo when given before endometrial destruction in premenopausal women with heavy menstrual bleeding. The following electronic databases were searched to April 2013 for published and unpublished randomised controlled trials that met the inclusion criteria: the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL and PsycINFO.Other electronic sources of trials included trial registers for ongoing and

  10. [Endometrial cancer in young patients: report of 17 cases].

    PubMed

    Dudnyikova, Anna; Horváth, Katalin; Pete, Imre

    2013-09-01

    Endometrial cancer of young (less then 40 years old) patients comprises 4-5% of all endometrial cancers in Hungary. The majority of patients did not give birth yet, so fertility sparing is very important. Fertility sparing treatment is possible if the tumor's histology is endometrial type and Grade 1 (well differentiated). The tumor localizes only to the endometrium and there is no myometrium infiltration. The authors present 17 cases of patients treated at the Department of Gynecology of National Institute of Oncology (Budapest, Hungary). In 3 cases conservative therapy (progesterone treatment) was possible, and 14 patients had to undergo surgery, because conservative treatment did fail. Of 17 patients 14 were never pregnant. The average patient's age was 32.35 ± 4.27 years. The mean body weight was 93.13 ± 30.79 kg (from 58 kg up to 147 kg); in 7 cases BMI (body mass index) was more than 30. After surgery histological examination had revealed 2 cases with normal ovaries, 1 case of simple cyst and 1 case of malignant ovarian tumor (serous adenocarcinoma, Grade 2), and 10 cases of polycystic ovaries associated with endometrial cancer. Of 3 cases that had only curettage, the endometrial cancer was Grade 1, and in 1 case radiological imaging showed simplex ovarian cyst. The authors' findings concerning young endometrial cancer patients confirm the results published in the literature. In cases suitable for fertility sparing treatment it is not sufficient to concentrate only on endometrial findings, but is very important to focus on the therapy of cystic ovaries (80% of which is PCO), obesity and diabetes mellitus as well.

  11. [The premalignant disease of the endometrium: endometrial intraepithelial neoplasia].

    PubMed

    Francz, Mónika

    2008-03-01

    The WHO 1994 classification for endometrial hyperplasias is based on the morphologic features of the lesions. This system characterizes the nuclear cytologic morphology as typical or atypical and describes the glandular architectural pattern as simple or complex. The main problem of this classification is the poor reproducibility. Although the predictive value of the atypical category is high, there are many typical hyperplasia cases with cancer progression. Modern molecular data related to endometrial tumorigenesis and precise computerized morphometric analysis have identified the lesion that may be considered as a precursor of endometrioid adenocarcinoma. By definition, this endometrial intraepithelial neoplasia (EIN) is a clonal proliferation of architecturally and cytologically altered endometrial glands which are prone to malignant transformation to endometrioid (type I) endometrial adenocarcinoma. The morphometric basis of EIN diagnosis is the D-score (DS), which is a logical combination of three morphometric features that represent the glandular complexity, glandular volume and cytological alterations. PTEN inactivation and K-ras mutation are the earliest genetic changes that can be revealed in these lesions. Hyperplasia cases that do not fit into the EIN categories are considered as benign or hormonal endometrial hyperplasia. This is the theoretical basis of a new classification system in premalignant endometrial diseases. Retrospective clinical data proved the high predictive value of the EIN scheme, so the decision on therapy can be more established. The reproducibility is excellent with application of precise definitions and PTEN immunohistochemistry. In the "Blue book" published in 2003 the WHO introduces the new morphometric- and molecular-based EIN system, and recommends it as an alternative classification method.

  12. Prolactin-Elevating Antipsychotics and the Risk of Endometrial Cancer.

    PubMed

    Klil-Drori, Adi J; Yin, Hui; Abenhaim, Haim A; du Fort, Guillaume Galbaud; Azoulay, Laurent

    2017-06-01

    The use of antipsychotics may increase the risk of endometrial cancer through elevation of prolactin levels. We investigated the association between antipsychotics that are known to cause prolactin elevation and the risk of endometrial cancer. In data from the United Kingdom Clinical Practice Research Datalink, all women who were newly treated with antipsychotics from 1990-2013 were identified and followed until 2014. Within this cohort of antipsychotic users, a nested case-control analysis was conducted. Main exposure was nonsporadic use of prolactin-elevating antipsychotics, and the active comparator was prolactin-sparing antipsychotics. Cases were women newly diagnosed with endometrial cancer (ICD-10) matched with up to 20 controls on age, calendar year of cohort entry, linkability to the Hospital Episode Statistics repository, and duration of follow-up. Conditional logistic regression models were used to determine the association of prolactin-elevating antipsychotics and endometrial cancer compared with prolactin-sparing antipsychotics. All analyses were adjusted for relevant potential confounders, including smoking, obesity, and diabetes mellitus. The cohort included 65,930 women. During 366,112 person-years of follow-up, there were 139 cases of endometrial cancer (incidence rate: 38/100,000 person-years), which were matched to 1,603 controls. Compared with the use of prolactin-sparing antipsychotics, the use of prolactin-elevating antipsychotics was not associated with an increased risk of endometrial cancer (adjusted odds ratio [aOR] = 1.00; 95% CI, 0.68-1.48). These findings remained similar with different durations of use (≤ 1 year, aOR = 1.07; 95% CI, 0.64-1.78, and > 1 year, aOR = 0.95; 95% CI, 0.58-1.54) and were robust to various sensitivity analyses. Prolactin-elevating antipsychotics were not associated with an increased risk of endometrial cancer.

  13. Does Preoperative Diagnosis of Endometrial Hyperplasia Necessitate Intraoperative Frozen Section Consultation?

    PubMed

    Boyraz, Gokhan; Başaran, Derman; Salman, Mehmet C; Özgül, Nejat; Yüce, Kunter

    2016-11-01

    In women with endometrial hyperplasia, there is a risk for co-existent endometrial cancer when patients are subjected to immediate surgical treatment. The aim of this study was to investigate the frequency of endometrial cancer and the accuracy of frozen section analysis at the time of hysterectomy among patients with endometrial hyperplasia, to reveal whether or not a preoperative diagnosis of endometrial hyperplasia necessitates frozen section consultation. Retrospective cross-sectional study. A department database review was performed to identify patients who were subjected to hysterectomy with a preoperative diagnosis of endometrial hyperplasia, during the period from 2007 to 2014. The study group included 189 cases. The final pathological examination revealed endometrial cancer in 16 women (8.4%). The risk of cancer in patients with endometrial hyperplasia was 1 of 125 (0.8%) in simple hyperplasia without atypia, 1 of 21 (4.8%) in complex hyperplasia without atypia and 14 of 43 (32.5%) in atypical hyperplasia. Of women with cancer, 2 of 16 (12.5%) had high-risk features. Frozen section analysis was requested in 46 cases. Frozen sections helped to identify six out of 11 cases of endometrial cancer (54.5%). The sensitivity, specificity and positive and negative predictive values of frozen section analysis for the detection of endometrial cancer among women with endometrial hyperplasia were 54.4%, 97.2%, 85.7% and 87.5%, respectively. Although a significant proportion of patients with atypical endometrial hyperplasia are diagnosed with endometrial cancer following hysterectomy, most of these cases have low-risk features and do not require surgical staging. Additionally, intraoperative frozen section analysis if not helpful for diagnosing concurrent endometrial cancer in patients with endometrial hyperplasia. Therefore, it seems that patients with endometrial hyperplasia can be operated upon in settings with no available method for obtaining frozen sections

  14. Does Preoperative Diagnosis of Endometrial Hyperplasia Necessitate Intraoperative Frozen Section Consultation?

    PubMed Central

    Boyraz, Gokhan; Başaran, Derman; Salman, Mehmet C.; Özgül, Nejat; Yüce, Kunter

    2016-01-01

    Background In women with endometrial hyperplasia, there is a risk for co-existent endometrial cancer when patients are subjected to immediate surgical treatment. Aims The aim of this study was to investigate the frequency of endometrial cancer and the accuracy of frozen section analysis at the time of hysterectomy among patients with endometrial hyperplasia, to reveal whether or not a preoperative diagnosis of endometrial hyperplasia necessitates frozen section consultation. Study Design Retrospective cross-sectional study. Methods A department database review was performed to identify patients who were subjected to hysterectomy with a preoperative diagnosis of endometrial hyperplasia, during the period from 2007 to 2014. Results The study group included 189 cases. The final pathological examination revealed endometrial cancer in 16 women (8.4%). The risk of cancer in patients with endometrial hyperplasia was 1 of 125 (0.8%) in simple hyperplasia without atypia, 1 of 21 (4.8%) in complex hyperplasia without atypia and 14 of 43 (32.5%) in atypical hyperplasia. Of women with cancer, 2 of 16 (12.5%) had high-risk features. Frozen section analysis was requested in 46 cases. Frozen sections helped to identify six out of 11 cases of endometrial cancer (54.5%). The sensitivity, specificity and positive and negative predictive values of frozen section analysis for the detection of endometrial cancer among women with endometrial hyperplasia were 54.4%, 97.2%, 85.7% and 87.5%, respectively. Conclusion Although a significant proportion of patients with atypical endometrial hyperplasia are diagnosed with endometrial cancer following hysterectomy, most of these cases have low-risk features and do not require surgical staging. Additionally, intraoperative frozen section analysis if not helpful for diagnosing concurrent endometrial cancer in patients with endometrial hyperplasia. Therefore, it seems that patients with endometrial hyperplasia can be operated upon in settings with

  15. Endometrial cancer with congenital uterine anomalies: three case reports and a literature review.

    PubMed

    Gao, Jinping; Zhang, Jintian; Tian, Wenyan; Teng, Fei; Zhang, Huiying; Zhang, Xuhong; Wang, Yingmei; Xue, Fengxia

    2017-01-24

    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 three 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, in order to identify similarities and differences in clinicopathologic characteristics and prognosis between endometrial cancer associated with uterine anomalies, and normal uterus.

  16. Quantitative contrast-enhanced ultrasonography for the differential diagnosis of endometrial hyperplasia and endometrial neoplasms

    PubMed Central

    Liu, Ying; Xu, Yi; Cheng, Wen; Liu, Xinghan

    2016-01-01

    The present study aimed to investigate the feasibility of applying contrast-enhanced ultrasonography (CEUS) imaging technology for distinguishing between benign and malignant endometrial lesions, and to screen markers that could be correlated with the pathological results. In this study, endometrial diseases were diagnosed by biopsy under hysteroscopy and CEUS examinations. The intensity and time parameters of the time-intensity curve (TIC) were analyzed. The mean arrival time (AT), time-to-peak (TTP), rise time (RT), washout half-time and clearance half-time of malignant lesions were shorter than those of benign lesions (P<0.05), whereas the average peak intensity (PI) and enhancement intensity (EI) of malignant lesions were higher than those of benign lesions (P<0.05). The receiver operating characteristic curve showed the following cut-off values: PI, 29.2 dB; EI, 21.35 dB; AT, 12.75 sec; TTP, 26.75 sec; RT, 13.2 sec; clearance half-time, 89.3 sec; and washout half-time, 75.45 sec. The lesions with PI, an EI higher than that of the cut-off and lesions with an AT, TTP, RT, half clearing time and washout half-time shorter than the cut-off were considered malignant. The TTP, RT and half clearing time were negatively correlated with microvessel density (MVD), i.e., MVD was higher when the TTP, RT and half clearing time were shorter. Overall, changes in the enhancement and clearing of lesions could be quantitatively analyzed by CEUS TIC and further discriminate benign from malignant lesions. In the present study, CEUS appeared to indirectly reflect blood vessel changes inside the lesions and provided a pre-operative non-invasive fast imaging method for the diagnosis of endometrial disease. PMID:27895728

  17. Effectiveness of transcervical hysteroscopic endometrial resection based on the prevention of the recurrence of endometrial polyps in post-menopausal women.

    PubMed

    Jiménez-Lopez, Jesus S; Miguel, Ana Granado-San; Tejerizo-Garcia, Alvaro; Muñoz-Gonzalez, Jose L; Lopez-Gonzalez, Gregorio

    2015-01-01

    The objectives of this study were to determine the effectiveness the effectiveness of post-polypectomy hysteroscopic endometrial resection in preventing the recurrence of endometrial polyps in post-menopausal patients and analyse the complications and necessity of additional surgery in patients, in addition to their degree of satisfaction. A prospective longitudinal study of post-menopausal patients diagnosed with endometrial polyps was conducted including polypectomy and hysteroscopic endometrial resection following the therapeutic purposes (endometrial polyp removal) and prevention of recurrence of endometrial polyps. We evaluated the general condition and characteristics of the patients, including age, BMI, smoking habits, medical, surgical, and obstetrics history and menstrual status. The results were analysed at several time points, 6, 18, 42 and 60 months by hysteroscopy, including the presence of vaginal bleeding and/or possible intracavitary pathology. A total of 89.5% (n = 355) of our patients had profile factors associated with the increased incidence of endometrial polyps and hyperestrogenism (diabetes mellitus, hypertension and overweight); 89.5% (n = 355) of patients were overweight; 34% had grade I obesity. The surgical procedure was safe, with a 90% (n = 357) success rate without complications, which was higher than the 95-99.5% at the beginning and end time points of the study. Patient acceptance and satisfaction was 90 and 84%, respectively. Endometrial resection proved effective in preventing the recurrence of endometrial polyps. It is a safe and effective method. Post-menopausal bleeding reduces the presence of endometrial polyps. Patients reported satisfaction and acceptance of the procedure.

  18. Body Mass Index Genetic Risk Score and Endometrial Cancer Risk

    PubMed Central

    Prescott, Jennifer; Setiawan, Veronica W.; Wentzensen, Nicolas; Schumacher, Fredrick; Yu, Herbert; Delahanty, Ryan; Bernstein, Leslie; Chanock, Stephen J.; Chen, Chu; Cook, Linda S.; Friedenreich, Christine; Garcia-Closas, Monserrat; Haiman, Christopher A.; Le Marchand, Loic; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M.; Olson, Sara H.; Risch, Harvey A.; Shu, Xiao-Ou; Ursin, Giske; Yang, Hannah P.; Kraft, Peter; De Vivo, Immaculata

    2015-01-01

    Genome-wide association studies (GWAS) have identified common variants that predispose individuals to a higher body mass index (BMI), an independent risk factor for endometrial cancer. Composite genotype risk scores (GRS) based on the joint effect of published BMI risk loci were used to explore whether endometrial cancer shares a genetic background with obesity. Genotype and risk factor data were available on 3,376 endometrial cancer case and 3,867 control participants of European ancestry from the Epidemiology of Endometrial Cancer Consortium GWAS. A BMI GRS was calculated by summing the number of BMI risk alleles at 97 independent loci. For exploratory analyses, additional GRSs were based on subsets of risk loci within putative etiologic BMI pathways. The BMI GRS was statistically significantly associated with endometrial cancer risk (P = 0.002). For every 10 BMI risk alleles a woman had a 13% increased endometrial cancer risk (95% CI: 4%, 22%). However, after adjusting for BMI, the BMI GRS was no longer associated with risk (per 10 BMI risk alleles OR = 0.99, 95% CI: 0.91, 1.07; P = 0.78). Heterogeneity by BMI did not reach statistical significance (P = 0.06), and no effect modification was noted by age, GWAS Stage, study design or between studies (P≥0.58). In exploratory analyses, the GRS defined by variants at loci containing monogenic obesity syndrome genes was associated with reduced endometrial cancer risk independent of BMI (per BMI risk allele OR = 0.92, 95% CI: 0.88, 0.96; P = 2.1 x 10−5). Possessing a large number of BMI risk alleles does not increase endometrial cancer risk above that conferred by excess body weight among women of European descent. Thus, the GRS based on all current established BMI loci does not provide added value independent of BMI. Future studies are required to validate the unexpected observed relation between monogenic obesity syndrome genetic variants and endometrial cancer risk. PMID:26606540

  19. Management of nodal recurrences of endometrial cancer with IMRT

    PubMed Central

    Ho, Jennifer C.; Allen, Pamela K.; Jhingran, Anuja; Westin, Shannon N.; Lu, Karen H.; Eifel, Patricia J.; Klopp, Ann H.

    2016-01-01

    Objective Pelvic and paraortic lymph nodal regions are frequent sites of relapse in women with endometrial cancer who have not undergone adjuvant external beam radiation. We investigated outcomes after definitive management of nodal relapses of endometrial cancer with intensity modulated radiation therapy (IMRT). Methods Between 2002-2012, 38 patients with endometrial cancer who had no prior external beam radiation were treated definitively using IMRT for regionally confined pelvic or paraortic nodal recurrences. Thirteen (34%) had chemotherapy prior to radiation, and 21 (55%) received concurrent chemotherapy. The nodal basins were typically treated to 45-50 Gy, with a boost to the gross tumor to a median total of 64.7 Gy (range 59 – 73 Gy). Results The median overall survival from date of recurrence was 46.1 months and the 2-year survival was 71%. Patients who received concurrent chemotherapy had a significantly longer median survival (61.9 months versus 28.7 months, p=0.034). In-field failures were more frequent in patients who received chemotherapy prior to radiation, had a shorter recurrence-free interval, received a lower radiation dose, and had higher tumor grade. Three patients (8%) experienced grade 3-4 late gastrointestinal (GI) toxicity. Conclusions Long-term survival can be achieved in women with nodal recurrences of endometrial cancer. The use of concurrent chemotherapy and dose escalation with IMRT as feasible may improve survival for women with isolated nodal recurrences of endometrial cancer. PMID:26193429

  20. 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

  1. 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.

  2. Cervical cytology in serous and endometrioid endometrial cancer.

    PubMed

    Roelofsen, Thijs; Geels, Yvette P; Pijnenborg, Johanna M A; van Ham, Maaike A P C; Zomer, Saskia F; van Tilburg, Johanna M Wiersma; Snijders, Marc P M L; Siebers, Albert G; Bulten, Johan; Massuger, Leon F A G

    2013-07-01

    The aim of this study was to determine the frequency of abnormal cervical cytology in preoperative cervical cytology of patients diagnosed with uterine papillary serous carcinoma (UPSC) and endometrioid endometrial carcinoma (EEC). In addition, associations between abnormal cervical cytology and clinicopathologic factors were evaluated. In this multicentre study, EEC patients diagnosed at two hospitals from 1999 to 2009 and UPSC patients diagnosed at five hospitals from 1992 to 2009, were included. Revision of the histologic slides was performed systematically and independently by 3 gynecopathologists. Cervical cytology within six months before histopathologic diagnosis of endometrial carcinoma was available for 267 EEC and 80 UPSC patients. Cervical cytology with atypical, malignant, or normal endometrial cells in postmenopausal women was considered as abnormal cytology, specific for endometrial pathology. Abnormal cervical cytology was found in 87.5% of UPSC patients, compared with 37.8% in EEC patients. In UPSC, abnormal cytology was associated with extrauterine spread of disease (P=0.043). In EEC, abnormal cytology was associated with cervical involvement (P=0.034). In both EEC and UPSC patients, abnormal cervical cytology was not associated with survival. In conclusion, abnormal cervical cytology was more frequently found in UPSC patients. It was associated with extrauterine disease in UPSC patients, and with cervical involvement in EEC patients. More prospective research should be performed to assess the true clinical value of preoperative cervical cytology in endometrial cancer patients.

  3. Endometrial bleeding in postmenopausal women: with and without hormone therapy.

    PubMed

    Archer, David F

    2011-04-01

    The aim of this study was to present a review of the potential mechanisms involved in the occurrence of endometrial bleeding in postmenopausal women using hormone therapy. Selected literature on the incidence of bleeding in postmenopausal women using estrogen progestogen therapy was reviewed. The incidence of spotting and bleeding in women using continuous-combined hormone therapy was presented. Relevant articles related to the role of angiogenic factors and vasculogenesis in the endometrium, endometrial leukocytes, and endometrial metalloproteinases were used for the review. The cause or etiology of endometrial bleeding with hormone therapy is unknown. Several options are known to alter angiogenesis or be involved in tissue remodeling during normal menstruation. Vascular endothelial growth factor and thrombospondin-1 are proangiogenic and antiangiogenic factors that could cause dysfunction in vasculogenesis that could result in blood vessel fragility and bleeding. The role of pericytes in maintaining vessel morphology and integrity is discussed. Endometrial leukocytes and metalloproteinases are involved in normal menstruation, but their role in postmenopausal bleeding is not clear suggesting involvement of mechanisms in the bleeding. There is limited information on clinical investigation into the etiology of postmenopausal bleeding associated with hormone therapy. The major cause of hormone therapy-related bleeding is unknown. Alterations in angiogenic factors that could result in vascular dysfunction and vessel breakdown provide a working hypothesis as to the potential cause of vessel breakdown.

  4. Do endometrial cancer patients benefit from metformin intake?

    PubMed

    Lemańska, Agnieszka; Zaborowski, Mikołaj; Spaczyński, Marek; Nowak-Markwitz, Ewa

    2015-06-01

    Since metformin was reported to decrease overall cancer incidence and mortality and to have antiproliferative and antinvasive properties, we investigated the impact of metformin intake on survival in endometrial cancer patients. Medical records and survival data of 126 patients with endometrial cancer were analyzed retrospectively U Mann-Whitney and chi-square tests were applied to compare clinicopathological features. Kaplan Meier model with log-rank test was used to compare survival in the subgroups. Cox proportional hazard model was applied to analyze the relationships between particular factors and overall survival. 107 patients met study criteria and were divided into three groups: 1) patients with type 2 diabetes and metformin users (n = 30), 2) patients with type 2 diabetes and metformin non-users (n = 38), 3) patients without diabetes mellitus (n = 39). No difference in survival between metformin users versus metformin non-users (p = 0.86) was observed. Metformin intake, diabetes mellitus co morbidity, plasma glucose level and BMI appeared without influence on survival. When the analysis was restricted to the subgroup of type I endometrial cancer or to endometroid histological type, still neither metformin intake nor diabetes influenced the prognosis. Metformin intake does not alter overall survival in endometrial cancer patients. Diabetes mellitus has no influence on survival in endometrial cancer patients.

  5. CD44 expression in papillary serous endometrial carcinoma.

    PubMed

    Hosford, S; Elliott, J; Ma, Z-W; Majeste, R; Dubeshter, B

    2003-01-01

    The objective of this paper is to evaluate the relationship between CD44 expression and the clinicopathologic features of papillary serous endometrial cancer. CD44 expression was assessed in 32 cases of papillary serous endometrial carcinoma by standard immunohistochemical staining techniques. Clinicopathologic features including myometrial invasion, nodal metastases, tumor spread, stage, and the shedding of malignant cells on cervical cytology were reviewed. The Chi-square test was used for statistical analysis. CD44 was not expressed in 81% of patients with papillary serous endometrial carcinoma. Malignant cells were seen on cervical cytology in 68% of all cases with significantly more in the CD44-negative group (78% vs. 33%, P 0.05). CD44 expression was not related to stage, myometrial invasion, nodal involvement, or intraperitoneal spread. We conclude that the cell adhesion molecule CD44 is expressed infrequently in papillary serous endometrial carcinoma. Shedding of malignant cells on cervical cytology is common in papillary serous endometrial cancer and occurs more frequently in CD44-negative cases. CD44 expression doesn't appear to be related to known prognostic features such as nodal metastases or stage. The biologic aggressiveness of this tumor type may, in part, be related to its lack of CD44 expression.

  6. Management of nodal recurrences of endometrial cancer with IMRT.

    PubMed

    Ho, Jennifer C; Allen, Pamela K; Jhingran, Anuja; Westin, Shannon N; Lu, Karen H; Eifel, Patricia J; Klopp, Ann H

    2015-10-01

    Pelvic and paraortic lymph nodal regions are frequent sites of relapse in women with endometrial cancer who have not undergone adjuvant external beam radiation. We investigated outcomes after definitive management of nodal relapses of endometrial cancer with intensity modulated radiation therapy (IMRT). Between 2002-2012, 38 patients with endometrial cancer who had no prior external beam radiation were treated definitively using IMRT for regionally confined pelvic or paraortic nodal recurrences. Thirteen (34%) had chemotherapy prior to radiation, and 21 (55%) received concurrent chemotherapy. The nodal basins were typically treated to 45-50Gy, with a boost to the gross tumor to a median total of 64.7Gy (range 59-73Gy). The median overall survival from date of recurrence was 46.1months and the 2-year survival was 71%. Patients who received concurrent chemotherapy had a significantly longer median survival (61.9months versus 28.7months, p=0.034). In-field failures were more frequent in patients who received chemotherapy prior to radiation, had a shorter recurrence-free interval, received a lower radiation dose, and had higher tumor grade. Three patients (8%) experienced grade 3-4 late gastrointestinal (GI) toxicity. Long-term survival can be achieved in women with nodal recurrences of endometrial cancer. The use of concurrent chemotherapy and dose escalation with IMRT as feasible may improve survival for women with isolated nodal recurrences of endometrial cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    ClinicalTrials.gov

    2017-02-23

    Endometrial Adenocarcinoma; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Undifferentiated Carcinoma; 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

  8. Lower Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Promotes the Proliferation and Migration of Endometrial Carcinoma

    PubMed Central

    Xia, Xian; Wang, Jie; Liu, Yuan; Yue, Ming

    2017-01-01

    Background The incidence and death rates of endometrial cancer are alarmingly increasing. The diagnosis and treatment of endometrial cancer is crucial to decreasing mortality. Cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the adenosine triphosphate (ATP)-binding cassette transporter family and plays an essential role in anion regulation and tissue homeostasis of various epithelia. This study explored the expression of CFTR in endometrial carcinoma and the role of CFTR in proliferation and migration of endometrial carcinoma cells. Material/Methods Immunohistochemistry and real-time (RT)-PCR were used to test the expression of CFTR in normal endometrium and endometrial carcinoma. CFTR inhibitor was used to restrain the expression of CFTR on the endometrial carcinoma, the effects on the proliferation and migration of endometrial carcinoma cells were also studied. RT-PCR was performed to test the expression of mir-125b after restraining CFTR. Proliferation and migration capability of endometrial carcinoma cells were detected after transfection of endometrial carcinoma cells with mir-125b mimic. Results Compared with cells from normal endometrium, the expression of CFTR was significantly upregulated in endometrial carcinoma cells. After adding CFTR(inh)172, the capability for proliferation and transfer of endometrial carcinoma cells was strengthened, the expression of mir-125b was reduced, and after transfection with mir-125b mimics entering the endometrial carcinoma cells, the ability of the proliferation and transfer of endometrial carcinoma cells was also reduced. Conclusions The high expression of CFTR in the endometrial carcinoma cells played a pivotal role in restraining the proliferation and transfer of endometrial carcinoma cells. PMID:28225751

  9. Lower Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Promotes the Proliferation and Migration of Endometrial Carcinoma.

    PubMed

    Xia, Xian; Wang, Jie; Liu, Yuan; Yue, Ming

    2017-02-22

    BACKGROUND The incidence and death rates of endometrial cancer are alarmingly increasing. The diagnosis and treatment of endometrial cancer is crucial to decreasing mortality. Cystic fibrosis transmembrane conductance regulator (CFTR) belongs to the adenosine triphosphate (ATP)-binding cassette transporter family and plays an essential role in anion regulation and tissue homeostasis of various epithelia. This study explored the expression of CFTR in endometrial carcinoma and the role of CFTR in proliferation and migration of endometrial carcinoma cells. MATERIAL AND METHODS Immunohistochemistry and real-time (RT)-PCR were used to test the expression of CFTR in normal endometrium and endometrial carcinoma. CFTR inhibitor was used to restrain the expression of CFTR on the endometrial carcinoma, the effects on the proliferation and migration of endometrial carcinoma cells were also studied. RT-PCR was performed to test the expression of mir-125b after restraining CFTR. Proliferation and migration capability of endometrial carcinoma cells were detected after transfection of endometrial carcinoma cells with mir-125b mimic. RESULTS Compared with cells from normal endometrium, the expression of CFTR was significantly upregulated in endometrial carcinoma cells. After adding CFTR(inh)172, the capability for proliferation and transfer of endometrial carcinoma cells was strengthened, the expression of mir-125b was reduced, and after transfection with mir-125b mimics entering the endometrial carcinoma cells, the ability of the proliferation and transfer of endometrial carcinoma cells was also reduced. CONCLUSIONS The high expression of CFTR in the endometrial carcinoma cells played a pivotal role in restraining the proliferation and transfer of endometrial carcinoma cells.

  10. Long-term incidence of hysterectomy following endometrial resection or endometrial ablation for heavy menstrual bleeding.

    PubMed

    Kalampokas, Emmanouil; McRobbie, Sarah; Payne, Fiona; Parkin, David E

    2017-10-01

    To estimate the incidence of hysterectomy following endometrial resection or endometrial ablation (ERA). The present retrospective study enrolled women who underwent ERA for benign heavy menstrual bleeding (HMB) at Aberdeen Royal Infirmary, UK, between February 1, 1990, and December 31, 1997; follow-up data to the end of 2015 were included from the pathology laboratory report system from the single pathology laboratory in the region. Data were compared between patients who did or did not require a hysterectomy after ERA. There were 901 patients who underwent ERA for HMB during the study period. The mean age of patients was 42.3 ± 5.7 years; of the patients included, 206 (22.9%) women underwent hysterectomy and these patients had a mean age of 40.1 years. Of the patients who had hysterectomies, 155 (75.2%) did so in the first 5 years following ERA, 31 (15.0%) did within 6-10 years, 11 (5.3%) did within 11-15 years, and 9 (4.4%) did within 16-20 years. In total, 51 (24.8%) of these patients had hysterectomies within 6-25 years of ERA. A significant majority of women who underwent ERA for HMB did not require hysterectomy up to 25 years after the procedure. © 2017 International Federation of Gynecology and Obstetrics.

  11. GnRH analogues may increase endometrial Hoxa10 promoter methylation and affect endometrial receptivity.

    PubMed

    Li, Fei; Zhang, Ming; Zhang, Yuanzhen; Liu, Teng; Qu, Xinlan

    2015-01-01

    The present study aimed to investigate whether gonadotropin-releasing hormone analogues (GnRH-as), including GnRH agonists and antagonists, affect endometrial homeobox (Hox) a10 DNA methylation during the implantation window in mice. GnRH analogue mouse models were used and were treated with either human menopausal gonadotropin (HMG) and a GnRH agonist or HMG and a GnRH antagonist. Uterus samples were collected 48 h after GnRH analogue treatment or ovulation. Bisulfite sequencing polymerase chain reaction (PCR), quantitative-PCR and western blot analysis were performed to assess Hoxa10 and integrin β3 expression. Scanning electron microscope analyses were conducted to analyze pinopode development. Compared with the natural cycle control mice, mice in the GnRH analogue groups were found to exhibit increased levels of methylation at the Hoxa10 promoter, decreased Hoxa10 mRNA and protein expression and disrupted pinopode development. These findings suggest that GnRH-as may be associated with altered Hoxa10 DNA methylation, thus GnRH-as may affect uterine Hoxa10 expression and endometrial receptivity.

  12. Association of the Apolipoprotein E 2 Allele with Concurrent Occurrence of Endometrial Hyperplasia and Endometrial Carcinoma

    PubMed Central

    Ivanova, Tatiana I.; Krikunova, Ludmila I.; Ryabchenko, Nikolay I.; Mkrtchyan, Liana S.; Khorokhorina, Vera A.; Salnikova, Lyubov E.

    2015-01-01

    Genes encoding proteins with antioxidant properties may influence susceptibility to endometrial hyperplasia (EH) and endometrial carcinoma (ECa). Patients with EH (n = 89), EH concurrent with ECa (n = 76), ECa (n = 186), and healthy controls (n = 1110) were genotyped for five polymorphic variants in the genes involved in metabolism of lipoproteins (APOE Cys112Arg and Arg158Cys), iron (HFE Cys282Tyr and His63Asp), and catecholamines (COMT Val158Met). Patients and controls were matched by ethnicity (all Caucasians), age, body mass index (BMI), and incidence of hypertension and diabetes. The frequency of the APOE E 2 allele (158Cys) was higher in patients with EH + ECa than in controls (P = 0.0012, P Bonferroni = 0.018, OR = 2.58, 95% CI 1.49–4.45). The APOE E 4 allele (112Arg) was more frequently found in patients with EH than in controls and HFE minor allele G (63Asp) had a protective effect in the ECa group, though these results appeared to be nonsignificant after correction for multiple comparisons. The results of the study indicate that E 2 allele might be associated with concurrent occurrence of EH and ECa. PMID:25741405

  13. 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.

  14. Management of stage II endometrial adenocarcinoma

    SciTech Connect

    Trimble, E.L.; Jones, H.W. III

    1988-03-01

    Charts of 36 patients with clinical stage II endometrial adenocarcinoma over ten years were reviewed. All were staged before any treatment, in accordance with International Federation of Gynecology and Obstetrics (FIGO) guidelines. Although details of treatment varied, two main protocols were used. Fourteen patients were treated with the standard protocol involving external whole-pelvis radiation, followed by intracavitary cesium and then hysterectomy. In 1981, a modified protocol was introduced, which called for a hysterectomy immediately following intrauterine and vaginal cesium. External radiation therapy was given only to those patients found to have deep myometrial invasion or cervical involvement. Of 14 patients treated by this protocol, seven had no surgical indication for postoperative external radiation. There was no increase in recurrence in these patients, and the five-year survival rate was 76% for patients treated with the modified protocol compared with 65% for those who had standard therapy. Morbidity related to external radiation therapy occurred in two patients with the standard protocol and one patient who received pelvic radiation on the modified protocol.

  15. [Survival and recurrence of endometrial adenocarcinoma].

    PubMed

    Sinistrero, G; Sismondi, P; Zola, P; Gribaudo, S; Danese, S; Bellora, M G

    1994-05-01

    444 endometrial carcinomas were retrospectively reviewed. Disease-free survival (DFS) was 83.6% at five years and 80.5% at ten years. 349 T1 cancers were treated by TAH-BSO and post-operative irradiation; 22.6% of them were over-staged. DFS ranged from 100% to 91% in 270 low-risk T1 patients, dropping to 84% in intermediate risk patients and to 44% in high-risk patients. DFS was 93% and 66% in the patients overstaged as pT2 and pT3, respectively; it was 82% for ovarian spread and 45% for pelvic peritoneum/parametrium invasion. T2-T3 patients were treated with preoperative irradiation and bilateral hysterectomy. DFS was 90.5% vs. 72.2% and 2/2 vs. 3/7 when the lesion was understaged. The results of irradiation were similar to literature data, but 53% of patients (all in poor general conditions and/or very old) died from associated diseases. Relapses were observed in 13.6% of cases (62/444 patients); 29 (6%) were local recurrences and 33 (7.6%) were distant metastases, which correlated well with recurrences and 33 (7.6%) were distant metastases, which correlated well with risk factors. Severe complication (G3) were observed in 6.3% of cases.

  16. Loss of heterozygosity in endometrial carcinoma.

    PubMed

    Velasco, Ana; Pallares, Judit; Santacana, Maria; Yeramian, Andre; Dolcet, Xavier; Eritja, Nuria; Puente, Soraya; Sorolla, Anabel; Llecha, Nuria; Matias-Guiu, Xavier

    2008-07-01

    Inactivation of a tumor suppressor gene typically occurs in two steps, thus fulfilling Knudson hypothesis. One "hit" is frequently a point mutation or a small deletion. The other alteration is usually a large genomic loss of part of a gene, or even part of a chromosome, or the whole chromosome. However, it is not clear which of these two events occurs first. Loss of heterozygosity (LOH) analysis allows the identification of one of the 2 hits. Although microsatellite polymerase chain reaction is the technique most frequently used to assess LOH, other different approaches can also be used. The LOH can also be assessed by restriction fragment length polymorphism analysis, single strand conformation polymorphism analysis, oligonucleotide microarrays capable to simultaneously determine the genotype of thousands of single-nucleotide polymorphism (single-nucleotide polymorphism arrays), comparative genomic hybridization, multiplex amplification and probe hybridization, and multiplex ligation-dependent probe amplification. In this article, the authors review the results obtained with molecular analysis of LOH in the understanding of development and progression of endometrial carcinoma. Particular attention is given to: (1) the presence of widespread LOH in nonendometrioid carcinoma, probably reflecting the existence of chromosomal instability; and (2) specific LOH patterns associated with some clinicopathologic features.

  17. Endometrial ablation in the management of abnormal uterine bleeding.

    PubMed

    Laberge, Philippe; Leyland, Nicholas; Murji, Ally; Fortin, Claude; Martyn, Paul; Vilos, George; Leyland, Nicholas; Wolfman, Wendy; Allaire, Catherine; Awadalla, Alaa; Dunn, Sheila; Heywood, Mark; Lemyre, Madeleine; Marcoux, Violaine; Potestio, Frank; Rittenberg, David; Singh, Sukhbir; Yeung, Grace

    2015-04-01

    Abnormal uterine bleeding (AUB) is the direct cause of a significant health care burden for women, their families, and society as a whole. Up to 30% of women will seek medical assistance for the problem during their reproductive years. To provide current evidence-based guidelines on the techniques and technologies used in endometrial ablation (EA), a minimally invasive technique for the management of AUB of benign origin. Members of the guideline committee were selected on the basis of individual expertise to represent a range of practical and academic experience in terms of both location in Canada and type of practice, as well as subspecialty expertise and general background in gynaecology. The committee reviewed all available evidence in the English medical literature, including published guidelines, and evaluated surgical and patient outcomes for the various EA techniques. Recommendations were established by consensus. Published literature was retrieved through searches of MEDLINE and The Cochrane Library in 2013 and 2014 using appropriate controlled vocabulary and key words (endometrial ablation, hysteroscopy, menorrhagia, heavy menstrual bleeding, AUB, hysterectomy). RESULTS were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English from January 2000 to November 2014. Searches were updated on a regular basis and incorporated in the guideline to December 2014. Grey (unpublished) literature was identifies through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). This document reviews the evidence regarding the available techniques and technologies for EA

  18. Combination analysis of Bub1 and Mad2 expression in endometrial cancer: act as a prognostic factor in endometrial cancer.

    PubMed

    Li, Lin; Xu, De-Bin; Zhao, Xiao-Li; Hao, Tian-Yu

    2013-07-01

    This study aimed to evaluate the diagnostic value of Bub1 and Mad2 together in endometrial cancer. Sixty-three patients with endometrial cancer, including EECs and NEECs, were examined statistically. Bub1 and Mad2 in patient tissues were detected by indirect streptavidin-biotin-peroxidase complex method. 39 cases (61.9 %) were in clinical stage I, 17 cases (27 %) in stage II, 5 (7.9 %) in stage III and 2 cases (3.2 %) in stage IV. Bub1 positive and Mad2 positive rate were identified in 18 and 54 patients. The lower positive of Bub1 and higher positive rate of Mad2 were related to clinical stage and histological grade of endometrial cancer (P = 0.009, 0.002, respectively), especially in NEECs. The expression of Bub1 was negatively correlated with Mad2 and Mtp53 (both P < 0.05). The expression of Mad2 with Mtp53 was positively correlated (P < 0.05). Statistically significant difference between Bub1/Mad2 expression and survival was discovered in endometrial cancer. Specificity and sensitivity of combination between Bub1 negative and Mad2 positive cases were higher than those alone in NEEC subtype. Bub1 and Mad2 are associated with histological differentiation, clinical stage and decreased postoperative survival in endometrial cancer. The combination analysis of Bub1 and Mad2 might be the valuable prognostic, even diagnostic clinicopathologic factor which can be applicable in routine examination.

  19. 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

  20. 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

  1. USP14 is a predictor of recurrence in endometrial cancer and a molecular target for endometrial cancer treatment

    PubMed Central

    Mooneyham, Ashley; Mullany, Sally; Zhao, Xianda; Shahi, Maryam; Richter, James; Klein, Molly; Chen, Liqiang; Ding, Rui; Konecny, Gottfried; Kommoss, Stefan; Winterhoff, Boris; Ghebre, Rahel; Bazzaro, Martina

    2016-01-01

    Endometrial adenocarcinoma is the most common gynecologic malignancy in the United States. Most endometrial cancer cases are diagnosed at an early stage and have good prognosis. Unfortunately a subset of patients with early stage and low grade disease experience recurrence for reasons that remain unclear. Recurrence is often accompanied by chemoresistance and high mortality. Deubiquitinating enzymes (DUBs) are key components of the ubiquitin-dependent protein degradation pathway and act as master regulators in a number of metabolic processes including cell growth, differentiation, and apoptosis. DUBs have been shown to be upregulated in a number of human cancers and their aberrant activity has been linked to cancer progression, initiation and onset of chemoresistance. Thus, selective inhibition of DUBs has been proposed as a targeted therapy for cancer treatment. This study suggests the DUB USP14 as a promising biomarker for stratifying endometrial cancer patients at diagnosis based on their risk of recurrence. Further USP14 is expressed along with the marker of proliferation Ki67 in endometrial cancer cells in situ. Lastly, pharmacological targeting of USP14 with the FDA approved small-molecule inhibitor VLX1570, decreases cell viability in chemotherapy resistant endometrial cancer cells with a mechanism consistent with cell cycle arrest and caspase-3 mediated apoptosis. PMID:27121063

  2. USP14 is a predictor of recurrence in endometrial cancer and a molecular target for endometrial cancer treatment.

    PubMed

    Vogel, Rachel Isaksson; Pulver, Tanya; Heilmann, Wiebke; Mooneyham, Ashley; Mullany, Sally; Zhao, Xianda; Shahi, Maryam; Richter, James; Klein, Molly; Chen, Liqiang; Ding, Rui; Konecny, Gottfried; Kommoss, Stefan; Winterhoff, Boris; Ghebre, Rahel; Bazzaro, Martina

    2016-05-24

    Endometrial adenocarcinoma is the most common gynecologic malignancy in the United States. Most endometrial cancer cases are diagnosed at an early stage and have good prognosis. Unfortunately a subset of patients with early stage and low grade disease experience recurrence for reasons that remain unclear. Recurrence is often accompanied by chemoresistance and high mortality.Deubiquitinating enzymes (DUBs) are key components of the ubiquitin-dependent protein degradation pathway and act as master regulators in a number of metabolic processes including cell growth, differentiation, and apoptosis. DUBs have been shown to be upregulated in a number of human cancers and their aberrant activity has been linked to cancer progression, initiation and onset of chemoresistance. Thus, selective inhibition of DUBs has been proposed as a targeted therapy for cancer treatment.This study suggests the DUB USP14 as a promising biomarker for stratifying endometrial cancer patients at diagnosis based on their risk of recurrence. Further USP14 is expressed along with the marker of proliferation Ki67 in endometrial cancer cells in situ. Lastly, pharmacological targeting of USP14 with the FDA approved small-molecule inhibitor VLX1570, decreases cell viability in chemotherapy resistant endometrial cancer cells with a mechanism consistent with cell cycle arrest and caspase-3 mediated apoptosis.

  3. Tubal Pregnancy Associated with Endometrial Carcinoma after In Vitro Fertilization Attempts

    PubMed Central

    Bayoglu Tekin, Yesim; Guvendag Guven, Emine Seda; Sehitoglu, Ibrahim; Guven, Suleyman

    2014-01-01

    Endometrial carcinoma is rarely seen during reproductive ages and commonly related to infertility, polycystic ovarian syndrome (PCOS), and obesity. Pregnancy associated endometrial carcinoma is even rarer and this is the second case reported in the literature concerning tubal pregnancy associated endometrial carcinoma. We present a case of a 36-year-old woman with a history of PCOS, infertility, and several attempts of ovulation induction and in vitro fertilization, who was diagnosed with tubal pregnancy and a well differentiated endometrial carcinoma. We also review the literature about pregnancy associated endometrial carcinoma in the first trimester. PMID:25614844

  4. New endometrial ablation techniques for treatment of menorrhagia.

    PubMed

    Bradley, Linda D

    2004-01-01

    Endometrial ablation is an excellent alternative to hysterectomy in women with menorrhagia and small intramural fibroids. Preoperative evaluation, which includes office hysteroscopy or saline infusion sonography, is critical to patient management and choice of procedure. A vast array of endometrial ablation technology is available currently that includes balloon therapy, cryosurgery hot circulating saline, bipolar impedance technology, and microwave: (1) ThermaChoice UTB System (Gynecare, Inc., Somerville, NJ, USA), (2) Uterine Balloon Therapy (UBT) System, HerOption Uterine Cryoblation Therapy System (American Medical Systems, Inc., Minnetonka, MN, USA), (3) Hydro ThermAblator HTA System (BEI Medical/Boston Scientific, Natick, MA), (4) NovaSure System (Novacept, Palo Alto, CA, USA), and (5) Microsulis Microwave Endometrial Ablation (MEA) System (Microsulis Medical Ltd., Pompano Beach, FL, USA). Each method is described herein, and Summary of Safety and Effectiveness Data (SSED) data for each product are reviewed.

  5. Progesterone Receptor Action in Leiomyoma and Endometrial Cancer

    PubMed Central

    Kim, J. Julie; Sefton, Elizabeth C.; Bulun, Serdar E.

    2013-01-01

    Progesterone is a key hormone in the regulation of uterine function. In the normal physiological context, progesterone is primarily involved in remodeling of the endometrium and maintaining a quiescent myometrium. When pathologies of the uterus develop, specifically, endometrial cancer and uterine leiomyoma, response to progesterone is usually altered. Progesterone acts through mainly two isoforms of the progesterone receptor (PR), PRA and PRB which have been reported to exhibit different transcriptional activities. Studies examining the expression and function of the PRs in the normal endometrium and myometrium as well as in endometrial cancer and uterine leiomyoma are summarized here. The clinical use of progestins and the transcriptional activity of the PR on genes specific to endometrial cancer and leiomyoma are described. An increased understanding of the differential expression of PRs and response to progesterone in these two diseases is critical in order to develop more efficient and targeted therapies. PMID:20374701

  6. IMP2 expression distinguishes endometrioid from serous endometrial adenocarcinomas.

    PubMed

    Zhang, Liping; Liu, Yuxin; Hao, Suyang; Woda, Bruce A; Lu, Di

    2011-06-01

    Among various endometrial adenocarcinomas, endometrioid carcinoma can be very difficult to separate from serous carcinomas. Various biomarkers have been studied with proven value, including p53, Ki-67, and p16. In this study, we present data on another biomarker, IMP2, which we believe is sensitive and specific. Using 320 endometrial biopsy cases, we demonstrate that IMP2 is normally expressed in all proliferative and inactive endometrial glandular cells. The pattern of such expression is unchanged in serous carcinomas. IMP2 expression is, however, lost in all cases of endometrioid carcinomas by at least 25% to >95% of tumor cell populations. Therefore, loss of IMP2 expression can differentiate endometrioid from serous carcinomas. Such finding of IMP2 expression remained the same in mixed endometrioid and serous carcinomas; IMP2 expression is lost in all endometrioid components by at least 25% of tumor cell population, whereas it remained diffuse and strong in all serous components of carcinomas.

  7. Improving survival after endometrial cancer: the big picture.

    PubMed

    Kwon, Janice S

    2015-07-01

    To improve survival in women with endometrial cancer, we need to look at the "big picture" beyond initial treatment. Although the majority of women will be diagnosed with early stage disease and are cured with surgery alone, there is a subgroup of women with advanced and high-risk early stage disease whose life expectancy may be prolonged with the addition of chemotherapy. Immunohistochemistry will help to identify those women with Lynch syndrome who will benefit from more frequent colorectal cancer surveillance and genetic counseling. If they happen to be diagnosed with colorectal cancer, this information has an important therapeutic implication. And finally, because the majority of women will survive their diagnosis of endometrial cancer, they remain at risk for breast and colorectal cancer, so these women should be counselled about screening for these cancers. These three interventions will contribute to improving the overall survival of women with endometrial cancer.

  8. ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer

    PubMed Central

    Colombo, Nicoletta; Creutzberg, Carien; Amant, Frederic; Bosse, Tjalling; González-Martín, Antonio; Ledermann, Jonathan; Marth, Christian; Nout, Remi; Querleu, Denis; Mirza, Mansoor Raza; Sessa, Cristiana

    2016-01-01

    Abstract The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11–13 December 2014 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of endometrial cancer. Before the conference, the expert panel prepared three clinically-relevant questions about endometrial cancer relating to the following four areas: prevention and screening, surgery, adjuvant treatment and advanced and recurrent disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. Results of this consensus conference, together with a summary of evidence supporting each recommendation, are detailed in this article. All participants have approved this final article. PMID:26645990

  9. Role of epigenomics in ovarian and endometrial cancers.

    PubMed

    Balch, Curtis; Matei, Daniela E; Huang, Tim H-M; Nephew, Kenneth P

    2010-06-01

    Ovarian cancer is the most lethal gynecologic malignancy and while constituting only 3% of all female cancers, it causes 14,600 deaths in the USA annually. Endometrial cancer, the most diagnosed and second-most fatal gynecologic cancer, afflicts over 40,000 US women annually, causing an estimated 7780 deaths in 2009. In both advanced ovarian and endometrial carcinomas, the majority of initially therapy-responsive tumors eventually evolve to a fully drug-resistant phenotype. In addition to genetic mutations, epigenetic anomalies are frequent in both gynecologic malignancies, including aberrant DNA methylation, atypical histone modifications and dysregulated expression of distinct microRNAs, resulting in altered gene-expression patterns favoring cell survival. In this article, we summarize the most recent hypotheses regarding the role of epigenetics in ovarian and endometrial cancers, including a possible role in tumor 'stemness' and also evaluate the possible therapeutic benefits of reversal of these oncogenic chromatin aberrations.

  10. Pathophysiology and management of endometrial hyperplasia and carcinoma.

    PubMed Central

    Fu, Y. S.; Gambone, J. C.; Berek, J. S.

    1990-01-01

    Endometrial cancer is currently the commonest pelvic malignancy affecting American women, most of whom share the same pathophysiologic basis, that is, unopposed estrogenic stimulation. The initial result of hyperestrogenism is the development of endometrial hyperplasia, which is reversible in most cases by appropriate hormonal therapy. Persistent stimulation eventually leads to atypical hyperplasia with nuclear atypia and invasive carcinoma. Because there is no cost-effective screening method for the detection of endometrial hyperplasia and carcinoma, it is essential to survey the high-risk population with appropriate diagnostic techniques. After diagnosis, therapy should be individualized based on pathologic findings (cell type and histologic grade) and extent of disease (International Federation of Gynaecologists and Obstetricians stage, depth of myometrial invasion, and pelvic and para-aortic lymph node status). Recent studies suggest that sex hormone receptors and nuclear DNA ploidy patterns provide useful prognostic information independent of histologic grade. Images PMID:2202159

  11. [Clinical analysis of postoperative radiotherapy for stage I endometrial cancer].

    PubMed

    Li, Z; Shen, W; Wang, J

    1998-05-01

    To evaluate the role and complications of adjuvant radiotherapy for stage I endometrial cancer after surgery. From May, 1986 to December, 1995, 20 patients with stage I endometrial cancer received total abdominal hysterectomy with bilateral salpingo-oophorectomy(TAH/BSO), and additional pelvic lymph node dissection in 5 cases. Most of the patients received radio therapy in 2-4 weeks after surgery. The radiation fields included pelvic lymph nodes with a total dose of 40-50 Gy. All the patients had survived for 10 years. Only one patient developed distant metastases. Acute radiation reaction was observed in all patients. Late radiation-induced damage occured in six patients and was severe in two. Postoperative radiotherapy in the management of stage I endometrial cancer is beneficial for the controal of local recurrence but has relatively high frequency of late radiation injury.

  12. Laparoscopic Assisted Surgical Staging (LASS) for Endometrial Cancer

    PubMed

    Vidal; Garza-Leal; Iglesias; Salvidar; Garza

    1994-08-01

    We report the first four cases of LASS for endometrial cancer in Mexico. Four patients diagnosed with endometrial adenocarcinoma were selected. These patients underwent peritoneal washing, vaginally assisted laparoscopic hysterectomy, bilateral salpingo-oophorectomy and pelvic biopsies. These biopsies included dissection of common iliac vessel, hypogastric and external vessels, and obturator nerve. An average of 10 nodes were obtained (8-11). In all patients both the nodes and the peritoneal washings were negative. The pathologic surgical staging was: three patients with IBG2 and one patient with IAG2. The patients were discharged on the sixth postoperative day, without complications. The follow-up is of 1 to 7 months and all are alive and without tumor activity. Patients with endometrial cancer often have associated obesity, diabetes and hypertension. For this reason the practice of minimally invasive surgery reduces morbidity. However, a full knowledge of anatomy, oncologic gynecology, and operative laparoscopy is imperative.

  13. Does metoclopramide exposure alter endometrial receptivity and decrease pregnancy rates?

    PubMed

    Çekmez, Yasemin; Korkmaz, Vakkas; Çakır, Aslı; Göçmen, Ahmet; Ergün, Yusuf; Gülşen, Serdar; Akpak, Yasam K

    2016-01-01

    The aim of this study was to investigate the effect of metoclopramide on endometrial receptivity with an immunohistochemical investigation of integrin β3 expression in pregnant rats. In the present study, the pregnant mice administrated by different doses of metoclopramide were used to explore the effect of metoclopramide on embryo implantation, especially on the endometrial receptivity. The statistical results showed that the number of implanted embryos was gradually declining along the increasing dose of metoclopramide. When the administrated dose of metoclopramide was 3 mg/kg per day, great changes were observed in the exposed uterine morphology and down-regulated integrin β3 were also found in high dose metoclopramide-exposed mice. Metoclopramide exposure, especially in high doses may alter endometrial receptivity by effecting integrin expression on decidual tissue which can decrease pregnancy rates. This drug should only be recommended for use during pregnancy when benefit outweighs the risk.

  14. Mifepristone-exposured human endometrial endothelial cells in vitro.

    PubMed

    Helmestam, Malin; Lindgren, Karin Elvine; Stavreus-Evers, Anneli; Olovsson, Matts

    2014-03-01

    The antiprogestin mifepristone has been used for more than 20 years as a medical alternative for early pregnancy termination. After mifepristone administration, significant changes have been observed in the endometrial vessels, with cell injury and cell death in capillary endothelial cells. In this study, the effect of mifepristone on human endometrial endothelial cells (HEECs) in vitro was evaluated using proliferation and viability assays, quantitative polymerase chain reaction of markers important for the regulation of angiogenesis, and by tube formation assay. There were no detectable effects of mifepristone on HEECs messenger RNA expression of the studied markers. Exposure to mifepristone did not alter tube formation. However, mifepristone exposure to HEECs cocultured with endometrial stromal cells significantly reduced the activity in the tube formation assay compared with mifepristone exposure of HEECs in monoculture. This implies that mifepristone causes changes in HEEC-associated angiogenic activity and that this effect is mediated through stromal cells via paracrine mechanisms.

  15. Mifepristone-Exposured Human Endometrial Endothelial Cells In Vitro

    PubMed Central

    Lindgren, Karin Elvine; Stavreus-Evers, Anneli; Olovsson, Matts

    2014-01-01

    The antiprogestin mifepristone has been used for more than 20 years as a medical alternative for early pregnancy termination. After mifepristone administration, significant changes have been observed in the endometrial vessels, with cell injury and cell death in capillary endothelial cells. In this study, the effect of mifepristone on human endometrial endothelial cells (HEECs) in vitro was evaluated using proliferation and viability assays, quantitative polymerase chain reaction of markers important for the regulation of angiogenesis, and by tube formation assay. There were no detectable effects of mifepristone on HEECs messenger RNA expression of the studied markers. Exposure to mifepristone did not alter tube formation. However, mifepristone exposure to HEECs cocultured with endometrial stromal cells significantly reduced the activity in the tube formation assay compared with mifepristone exposure of HEECs in monoculture. This implies that mifepristone causes changes in HEEC-associated angiogenic activity and that this effect is mediated through stromal cells via paracrine mechanisms. PMID:23885098

  16. Apposition to endometrial epithelial cells activates mouse blastocysts for implantation.

    PubMed

    Ruane, Peter T; Berneau, Stéphane C; Koeck, Rebekka; Watts, Jessica; Kimber, Susan J; Brison, Daniel R; Westwood, Melissa; Aplin, John D

    2017-09-01

    How do interactions between blastocyst-stage embryos and endometrial epithelial cells regulate the early stages of implantation in an in vitro model? Mouse blastocyst apposition with human endometrial epithelial cells initiates trophectoderm differentiation to trophoblast, which goes on to breach the endometrial epithelium. In vitro models using mouse blastocysts and human endometrial cell lines have proven invaluable in the molecular characterisation of embryo attachment to endometrial epithelium at the onset of implantation. Genes involved in embryonic breaching of the endometrial epithelium have not been investigated in such in vitro models. This study used an established in vitro model of implantation to examine cellular and molecular interactions during blastocyst attachment to endometrial epithelial cells. Mouse blastocysts developed from embryonic day (E) 1.5 in vitro were hatched and co-cultured with confluent human endometrial adenocarcinoma-derived Ishikawa cells in serum-free medium. A scale of attachment stability based on blastocyst oscillation upon agitation was devised. Blastocysts were monitored for 48 h to establish the kinetics of implantation, and optical sectioning using fluorescence microscopy revealed attachment and invasion interfaces. Quantitative PCR was used to determine blastocyst gene expression. Data from a total of 680 mouse blastocysts are reported, with 3-6 experimental replicates. T-test and ANOVA analyses established statistical significance at P < 0.05, P < 0.01 and P < 0.001. Hatched E4.5 mouse blastocysts exhibited weak attachment to confluent Ishikawa cells over the first 24 h of co-culture, with intermediate and stable attachment occurring from 28 h (E5.5 + 4 h) in a hormone-independent manner. Attached embryos fixed after 48 h (E6.5) frequently exhibited outgrowths, characterised morphologically and with antibody markers as trophoblast giant cells (TGCs), which had breached the Ishikawa cell layer. Beginning co-culture at E5

  17. Endometrial cancer implanted within a cesarean section scar.

    PubMed

    Baba, Tsukasa; Mandai, Masaki; Yamanishi, Yukio; Suzuki, Ayako; Kang, Hyun Sook; Konishi, Ikuo

    2011-03-01

    Several reports have documented adenocarcinoma arising from endometriotic implants within cesarean section (C-S) scars on the serosal surface of the uterus; however, endometrial cancer invading the C-S scar from the uterine cavity has not been described. We report a case of a grade 1 endometrioid adenocarcinoma 'drop' lesion invading a previous C-S scar with resultant cervical stromal invasion. Using both MR images and a thorough review of the pathology, the tumor at the C-S scar was determined to be an implant derived from a primary lesion at the uterine fundus. With increases in the incidence of both endometrial cancer and births by C-S, it is likely we will encounter more cases of iatrogenic implants of endometrial cancers in C-S scars.

  18. Pancreatic endometrial cyst mimics mucinous cystic neoplasm of the pancreas.

    PubMed

    Mederos, Michael A; Villafañe, Nicole; Dhingra, Sadhna; Farinas, Carlos; McElhany, Amy; Fisher, William E; Van Buren Ii, George

    2017-02-14

    Pancreatic cysts include a variety of benign, premalignant, and malignant lesions. Endometrial cysts in the pancreas are exceedingly rare lesions that are difficult to diagnose pre-operatively. This report describes the findings in a 43-year-old patient with a recent episode of acute pancreatitis who presented with a large cyst in the tail of the pancreas. Imaging demonstrated a loculated pancreatic cyst, and cyst fluid aspiration revealed an elevated amylase and carcinoembryonic antigen. The patient experienced an interval worsening of abdominal pain, fatigue, diarrhea, and a 15-pound weight loss 3 mo after the initial episode of pancreatitis. With concern for a possible pre-malignant lesion, the patient underwent a laparoscopic distal pancreatectomy with splenectomy, which revealed a 16 cm × 12 cm × 4 cm lesion. Final histopathology was consistent with an intra-pancreatic endometrial cyst. Here we discuss the overlapping imaging and laboratory features of pancreatic endometrial cysts and mucinous cystic neoplasms of the pancreas.

  19. 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.

  20. Infant feeding and the incidence of endometrial cancer.

    PubMed

    Xue, Fei; Hilakivi-Clarke, Leena A; Maxwell, G Larry; Hankinson, Susan E; Michels, Karin B

    2008-06-01

    Biological mechanisms could support both an inverse and a direct association between exposure to breast milk in infancy and the risk of cancer. Having been breast-fed has been investigated in relation to the risk of breast and other cancer sites, and conflicting results have been reported. The association between infant feeding and the risk of endometrial cancer has not been explored. From 1976 to 2004, we followed 74,757 cancer-free participants in the Nurses' Health Study who had not undergone hysterectomy. Information on infant feeding was self-reported by study participants. A total of 708 incident cases of endometrial cancer were diagnosed during follow-up. After adjusting for age, family history of endometrial cancer, birth weight, premature birth, and birth order, the incidence of endometrial cancer was not associated with ever having been breast-fed (hazards ratio, 0.94; 95% confidence interval, 0.79-1.11) or duration of having been breast-fed [hazards ratio (95% confidence interval): 1.11 (0.80-1.54), 0.84 (0.62-1.13), 1.02 (0.79-1.31), respectively, for < or =3, 4-8, and > or =9 months of having been breastfed; P for trend = 0.88]. There was no significant effect modification by menopausal status, anthropometric factors (somatotype at age 5 or 10 years, body mass index at age 18 years, or current body mass index), or by other early-life exposures (birth weight, premature birth or exposure to parental smoking in childhood). Additional adjustment for adulthood risk factors of endometrial cancer did not materially change the results. Having been breast-fed was not associated with the incidence of endometrial cancer in this cohort, but statistical power for analyses restricted to premenopausal women was limited.

  1. Childhood body mass index growth trajectories and endometrial cancer risk.

    PubMed

    Aarestrup, Julie; Gamborg, Michael; Tilling, Kate; Ulrich, Lian G; Sørensen, Thorkild I A; Baker, Jennifer L

    2017-01-15

    Previously, we found that excess weight already in childhood has positive associations with endometrial cancer; however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial cancer and its sub-types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6-14 years and born 1930-1989 formed the analytical population. BMI was transformed to age-specific z scores. Using linear spline multilevel models, each girl's BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25-7.99, 8.0-10.99, 11.0-14.0 years). Via a link to health registers, 1,020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain in BMI during childhood was positively associated with endometrial cancer but no differences between the different growth periods were detected in models adjusted for baseline BMI. The hazard ratios for the associations with overall growth during childhood per 0.1 z score increase were 1.15 (95% confidence interval [CI]: 1.07-1.24) for all endometrial cancers, 1.12 (95% CI: 1.04-1.21) for estrogen-dependent cancers, 1.16 (95% CI: 1.06-1.26) for endometrioid adenocarcinomas and 1.46 (95% CI: 1.16-1.84) for non-estrogen-dependent cancers. Growth in BMI in early life is positively linked to later endometrial cancer risk. We did not identify any sensitive childhood growth period, which suggests that excess gain in BMI during the entire childhood period should be avoided. © 2016 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

  2. 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.

  3. Robotic surgery in supermorbidly obese patients with endometrial cancer.

    PubMed

    Stephan, Jean-Marie; Goodheart, Michael J; McDonald, Megan; Hansen, Jean; Reyes, Henry D; Button, Anna; Bender, David

    2015-07-01

    Morbid obesity is a known risk factor for the development of endometrial cancer. Several studies have demonstrated the overall feasibility of robotic-assisted surgical staging for endometrial cancer as well as the benefits of robotics compared with laparotomy. However, there have been few reports that have evaluated robotic surgery for endometrial cancer in the supermorbidly obese population (body mass index [BMI], ≥50 kg/m(2)). We sought to evaluate safety, feasibility, and outcomes for supermorbidly obese patients who undergo robotic surgery for endometrial cancer, compared with patients with lower body mass indices. We performed a retrospective chart review of 168 patients with suspected early-stage endometrial adenocarcinoma who underwent robotic surgery for the management of their disease. Analysis of variance and univariate logistic regression were used to compare patient characteristics and surgical variables across all body weights. Cox proportional hazard regression was used to determine the impact of body weight on recurrence-free and overall survival. The mean BMI of our cohort was 40.9 kg/m(2). Median follow up was 31 months. Fifty-six patients, 30% of which had grade 2 or 3 tumors, were supermorbidly obese with a BMI of ≥50 kg/m(2) (mean, 56.3 kg/m(2)). A comparison between the supermorbidly obese and lower-weight patients demonstrated no differences in terms of length of hospital stay, blood loss, complication rates, numbers of pelvic and paraaortic lymph nodes retrieved, or recurrence and survival. There was a correlation between BMI and conversion to an open procedure, in which the odds of conversion increased with increasing BMI (P = .02). Offering robotic surgery to supermorbidly obese patients with endometrial cancer is a safe and feasible surgical management option. When compared with patients with a lower BMI, the supermorbidly obese patient had a similar outcome, length of hospital stay, blood loss, complications, and numbers of lymph

  4. The Use of Transvaginal Ultrasound in Type II Endometrial Cancer.

    PubMed

    Billingsley, Caroline C; Kenne, Kimberly A; Cansino, Catherine D; Backes, Floor J; Cohn, David E; O'Malley, David M; Copeland, Larry J; Fowler, Jeffrey M; Salani, Ritu

    2015-06-01

    To determine the use of the transvaginal ultrasound (TVUS) in postmenopausal women with type II endometrial cancer. A retrospective review was conducted for 173 women with pathology proven type II endometrial cancer at a single institution. Those who underwent preoperative TVUS were included, and the following data were obtained: endometrial stripe (EMS) measurement, uterine and/or adnexal findings, and uterine size/volume. Clinicopathologic factors were abstracted. Descriptive and regression analyses were performed. Fifty-eight women comprised the cohort, and the median age was 66.5 years (50-85 years). The most commonly reported symptom was postmenopausal bleeding in 53 patients (91.4%). The EMS was reported as thin (≤ 5 mm) or indistinct in 16 patients (27.5%). Approximately 60% of patients had 1 or more ultrasound abnormalities: intracavitary mass (31%), intracavitary fluid (12.1%), myometrial lesion (31.03%), and adnexal mass (12.1%). Poorly differentiated endometrioid cancer (53.45%) represented the predominant histology. Of the 16 (27.5%) women with a thin/indistinct EMS, 5 women (8.6%) did not have any abnormal ultrasound findings whatsoever. Women with type II endometrial cancer had a thin/indistinct EMS on TVUS in approximately 25% of cases. Lack of any ultrasound abnormality, including a thickened EMS, was noted in approximately 10% of patients. The use of TVUS, which has been of value in type I cancer, is limited in type II endometrial cancer. Therefore, endometrial sampling should be included in the evaluation of all women with postmenopausal bleeding, regardless of EMS thickness.

  5. Perineal use of talcum powder and endometrial cancer risk

    PubMed Central

    Karageorgi, Stalo; Gates, Margaret A.; Hankinson, Susan E.; De Vivo, Immaculata

    2010-01-01

    Background Several studies have reported a positive association between perineal use of talcum powder among adult women and ovarian cancer risk. However, the relationship between talcum powder use and other gynecologic malignancies such as endometrial cancer has not been examined, and little information is available on non-hormonal risk factors for endometrial cancer. Methods Perineal use of talcum powder was assessed in 1982 in the Nurses’ Health Study. Approximately 40% of women who responded to the questions about perineal use of talcum powder reported ever use. Cox proportional hazards models were used to estimate the incidence rate ratio of endometrial cancer and 95% confidence interval (CI), adjusted for body mass index and other potential confounders. We evaluated the relationship among all women and stratified by menopausal status. Results Our analysis included 66,028 women with 599 incident cases of invasive endometrial adenocarcinoma diagnosed between 1982 and 2004. Although no association was observed overall, the association varied by menopausal status (p-interaction=0.02) and a positive association was observed among postmenopausal women; ever use of talcum powder was associated with a 21% increase in risk of endometrial cancer (95% CI: 1.02, 1.44), while regular use (≥once/week) was associated with a 24% increase in risk (95% CI: 1.03, 1.48). In addition, we observed a borderline increase in risk with increasing frequency of use (p-trend=0.04). Conclusions Our results suggest that perineal talcum powder use increases the risk of endometrial cancer, particularly among postmenopausal women. Impact Future and larger studies are needed to confirm this association and investigate potential mechanisms. PMID:20406962

  6. Correlation between NDRG1 and PTEN expression in endometrial carcinoma.

    PubMed

    Chen, Jiawei; Li, Shuxia; Yang, Zhaorui; Lu, Guangzhong; Hu, Honghui

    2008-04-01

    N-myc Downstream-Regulated Gene 1 (NDRG1) is known as a differentiation-related gene that plays important roles in cell differentiation, organ formation, and embryonic development. NDRG1 has recently been shown to be associated with carcinogenesis and tumor progression in a wide variety of tumors. Phosphatase and tensin homolog deleted from chromosome (PTEN), a phosphatase and tensin homolog located on chromosome 10, is shown to be a tumor suppressor and is often mutated or deleted in various tumor cells, particularly in endometrial carcinoma. Using an immunohistochemical approach, we investigated the expression of NDRG1 and PTEN in normal endometrium, atypical hyperplasia, and endometrial carcinoma. All tumor tissues harvested in this study were derived from endometrioid carcinoma Type I, that were estrogen-related. Our results demonstrate that the expression of NDRG1 was up-regulated in 5/40 (12.5%), 18/34 (52.94%), and 86/103 (83.5%) normal endometrium, atypical hyperplasia, and endometrial carcinoma cases, respectively (P < 0.01), while in 6/40 (15%), 20/34 (58.82%), and 89/103 (86.41%) normal endometrium, atypical hyperplasia, and endometrial carcinoma cases, respectively. PTEN expression was significantly decreased (P < 0.01). Statistical analyzes demonstrated a positive correlation between NDRG1 up-regulation and PTEN down-regulation (P < 0.01). The expression of NDRG1 had no correlation with the differentiation degree of the tumor cells, lymph-node metastasis, and/or abdominal cavity implantation (P > 0.05). Our results indicated that development of endometrial carcinoma is associated with an overexpression of NDRG1 and the loss of PTEN expression. Identification of changes in the NDRG1 and PTEN expression may be a significant diagnostic tool for the early detection of endometrial carcinoma.

  7. Sonographic Evaluation for Endometrial Polyps: The Interrupted Mucosa Sign.

    PubMed

    Kamaya, Aya; Yu, Pauline Chang; Lloyd, Carla Ramas; Chen, Bertha H; Desser, Terry S; Maturen, Katherine E

    2016-11-01

    To evaluate the interrupted mucosa sign for identification of endometrial polyps, using pathologic confirmation as the reference standard, compared to other accepted sonographic findings. We reviewed 195 patients referred for pelvic sonographic evaluations for suspected endometrial polyps in this retrospective Institutional Review Board-approved study. Of these, 82 had tissue sampling of the endometrium and constituted the final study group. Patient data, including age, menopausal status, last menstrual period, and final pathologic diagnosis, were recorded. Sonograms were reviewed by 2 blinded board-certified radiologists for endometrial features, including thickness, echogenicity, vascularity, presence of a mass, and the interrupted mucosa sign. Descriptive statistics and multivariate logistic regression analysis were performed. The mean age of the patients was 44.99 (SD, 9.88) years, 79.1% of whom were premenopausal. Pathologic diagnosis confirmed polyps in 58 (70.73%). A single feeding vessel was visualized in 36 patients with polyps (62.07%), whereas the interrupted mucosa sign was visualized in 34 (58.62%). The presence of a feeding vessel, the interrupted mucosa sign, or both detected 48 (82.76%) of the polyps. In the multivariate analysis, only the interrupted mucosa sign was a statistically significant predictor of pathologic diagnosis of a polyp (P= .035), with an odds ratio of 3.83 (95% confidence interval, 1.10-13.29). Other sonographic findings were not independent predictors of a polyp: mass (P = .35), single feeding vessel (P = .31), endometrial thickness (P = .88), and endometrial echogenicity (P = .45). The sensitivity, specificity, and positive predictive value of the interrupted mucosa sign were 59%, 75%, and 85%, respectively. The interrupted mucosa sign is a promising sonographic sign for identification of endometrial polyps, with greater predictive power than previously described signs. It has the potential to improve the diagnostic performance

  8. Childhood body mass index growth trajectories and endometrial cancer risk

    PubMed Central

    Aarestrup, Julie; Gamborg, Michael; Tilling, Kate; Ulrich, Lian G.; Sørensen, Thorkild I.A.

    2016-01-01

    Previously, we found that excess weight already in childhood has positive associations with endometrial cancer; however, associations with changes in body mass index (BMI) during childhood are not well understood. Therefore, we examined whether growth in childhood BMI is associated with endometrial cancer and its sub‐types. A cohort of 155,505 girls from the Copenhagen School Health Records Register with measured weights and heights at the ages of 6–14 years and born 1930–1989 formed the analytical population. BMI was transformed to age‐specific z scores. Using linear spline multilevel models, each girl's BMI growth trajectory was estimated as the deviance from the average trajectory for three different growth periods (6.25–7.99, 8.0–10.99, 11.0–14.0 years). Via a link to health registers, 1,020 endometrial cancer cases were identified, and Cox regressions were performed. A greater gain in BMI during childhood was positively associated with endometrial cancer but no differences between the different growth periods were detected in models adjusted for baseline BMI. The hazard ratios for the associations with overall growth during childhood per 0.1 z score increase were 1.15 (95% confidence interval [CI]: 1.07–1.24) for all endometrial cancers, 1.12 (95% CI: 1.04–1.21) for estrogen‐dependent cancers, 1.16 (95% CI: 1.06–1.26) for endometrioid adenocarcinomas and 1.46 (95% CI: 1.16–1.84) for non‐estrogen‐dependent cancers. Growth in BMI in early life is positively linked to later endometrial cancer risk. We did not identify any sensitive childhood growth period, which suggests that excess gain in BMI during the entire childhood period should be avoided. PMID:27718528

  9. 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

  10. Endometrial assessment by transvaginal sonography and histological findings after D & C in women with postmenopausal bleeding.

    PubMed

    Conoscenti, G; Meir, Y J; Fischer-Tamaro, L; Maieron, A; Natale, R; D'Ottavio, G; Rustico, M; Mandruzzato, G

    1995-08-01

    A total of 149 women with postmenopausal bleeding underwent transvaginal sonography, hysteroscopy and dilatation and curettage in order to study the diagnostic accuracy of several ultrasound parameters in assessing endometrial pathology and to determine the most sensitive cut-off value of endometrial thickness for the exclusion of endometrial lesions. In distinguishing pathological from normal endometrium, transvaginal sonography showed a sensitivity of 69.3%, specificity of 82.7%, positive predictive value of 74.1% and negative predictive value of 72.1%. In detecting premalignant and malignant endometrial pathology, transvaginal sonography showed a sensitivity, specificity, positive predictive value and negative predictive value of 55%, 96.1%, 68.7% and 93.2%, respectively. Considering endometrial thickness as a single parameter, the most sensitive cut-off for defining normality was 4 mm; nevertheless, in the group of patients that had an endometrial thickness less than 4 mm, there was one case of malignancy (sensitivity, 95.2%; specificity, 49.4%; positive predictive value, 57.3%; and negative predictive value, 93.5%). Transvaginal sonography combined evaluation (morphology, thickness and color Doppler) showed a poor diagnostic accuracy in detecting endometrial pathology and in differentiating between endometrial benign lesions, endometrial polyps and adenocarcinoma in women with postmenopausal bleeding. Endometrial thickness evaluated with transvaginal sonography was preferable but not sensitive enough to exclude endometrial pathology.

  11. Life-style and metformin for the prevention of endometrial pathology in postmenopausal women.

    PubMed

    Campagnoli, Carlo; Abbà, Chiara; Ambroggio, Simona; Brucato, Tiziana; Pasanisi, Patrizia

    2013-02-01

    In western women, the endometrium is frequently exposed, even after menopause, to the endogenous hormonal stimulation. Such a stimulation increases the risk of pathologic conditions such as endometrial hyperplasia and type I (endometrioid) endometrial adenocarcinoma. Metabolic syndrome, obesity, insulin resistance and type II diabetes promote the endometrial stimulation, and are recognized risk factors for endometrial cancer. Furthermore, chronic hyperinsulinemia linked both to obesity and metabolic syndrome influences endometrial proliferation through direct and indirect actions. Intentional weight loss, calorie restriction and physical activity are associated with a reduced risk of the endometrial pathology. Biological mechanisms include reduction in insulin and sex steroid hormone levels. In addition to life-style modifications, the antidiabetic metformin may be proposed as preventive agent. Metformin reduces the metabolic syndrome, lowers insulin and testosterone levels in postmenopausal women, and it is a potent inhibitor of endometrial cancer cell proliferation.

  12. Current Issues in the Diagnosis and Treatment of Endometrial Carcinoma.

    PubMed

    Stubert, J; Gerber, B

    2016-02-01

    Endometrial carcinoma is the most common carcinoma of the female genital tract. Its most important clinical sign is postmenopausal bleeding. An endometrial biopsy is essential for diagnosis. Treatment decisions are governed by tumour risk assessment and patient comorbidity, which is often present. Pelvic and paraaortic lymph node dissection is unnecessary in low risk cases (definition: pT1 a, G1/2) and adjuvant radiotherapy and systemic treatments are usually avoidable. Treatment of high-risk patients (G3 and/or pT1b) and palliative cases is difficult and not well standardised. New molecular-based subtype classification may help treatment decision making in future.

  13. 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

  14. [Endometrial ossification: a report of four cases and literature review].

    PubMed

    Nevarez Bernal, Roberto; Vilchis Nava, Pablo; Kably Ambe, Alberto

    2007-03-01

    Endometrial ossification is a rare endometrial pathology. Its predisposing factors include history of uterine curettage to metabolic abnormalities. It usually presents in patients with secondary infertility and history of first trimester pregnancy loss, accompanied by severe dysmenorrhea and dyspareunia. The diagnosis is suspected by OB-GYN history and USG findings, therapeutic strategies range from D&C to hysterectomy, we propose diagnosis and management by hysteroscopy in order to preserve future fertility and minimize uterine damage. A review of four cases during 1985-2004 from a large assisted reproduction center in Mexico City is presented.

  15. [Laparoscopic hysterectomy in the management of endometrial cancer].

    PubMed

    Seracchioli, R; Fabbri, E; Guerrini, M; Mignemi, G; Venturoli, S

    2006-10-01

    Endometrial carcinoma is the most commonly reported gynaecologic malignancy in industrialized countries. Traditionally the surgical treatment of endometrial cancer is total abdominal hysterectomy, bilateral salpingo-oophorectomy, and peritoneal washing cytology. Alternative surgical procedures have been proposed compared to abdominal hysterectomy: increased number of issues about laparoscopy shows the common trend to use this technique. Literature largely described advantages of the laparoscopic procedure compared to abdominal and vaginal surgery. Long-term follow-up series are not available; further investigation into survival and recurrence rates is indicated.

  16. Computational analysis of endometrial photocoagulation with diffusing optical device.

    PubMed

    Kwon, Jinhee; Lee, Chang-Yong; Oh, Junghwan; Kang, Hyun Wook

    2013-01-01

    A balloon-catheter optical diffuser for endometrial treatment was evaluated with computational thermal analysis. Various catheter materials and dimensions were implemented to identify the optimal design for the device. Spatial and temporal development of temperature during 30-sec irradiation of 532-nm light demonstrated thermal insulation effects of polyurethane on temperature increase up to 384 K, facilitating the irreversible denaturation. The current model revealed the degree of thermal coagulation 13% thicker than experimental results possibly due to lack of tissue dynamics and light intensity distribution. In combination with photon distribution, the analytical simulation can be a feasible tool to optimize the new optical diffuser for efficient and safe endometrial treatment.

  17. Paraneoplastic cerebellar degeneration as a marker of endometrial cancer recurrence.

    PubMed

    Lie, Geoffrey; Morley, Thomas; Chowdhury, Muhammad

    2016-05-18

    An 84-year-old woman developed a cerebellar syndrome having undergone a total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometrial cancer 1 year previously. She was found to be anti-Yo antibody positive and was diagnosed with paraneoplastic cerebellar degeneration (PCD). A subsequent positron emission tomography scan and lymph node biopsy identified recurrence of her endometrial cancer. This case illustrates how PCD can be an indicator of cancer recurrence, underlines the significance of PCD as a prompt to search for underlying malignancy, and highlights the difficulties PCD poses to the clinician in terms of diagnosis and management.

  18. Endometrial stem cells: clinical application and pathological roles.

    PubMed

    Xu, Yanping; Zhu, Huiting; Zhao, Dongni; Tan, Jichun

    2015-01-01

    Adult stem cells occur in human endometrium. Menstrual-blood derived stem cells (MenSCs) are mesenchymal stem cells that can be obtained in a non-invasive manner. Due to their rapid proliferation rate, low immunogenicity, and low tumorigenicity, MenSCs are used extensively in tissue engineering. They can be induced into multiple cell lineages under certain conditions. MenSCs contribute to tissue repair via several different mechanisms, highlighting their great promise in clinical applications. Endometrial stem cells may also be used to shed light on the pathogenesis of endometriosis and endometrial carcinoma. This review will cover recent progress in this field.

  19. Endometrial pathology in postmenopausal tamoxifen treatment: comparison between gynaecologically symptomatic and asymptomatic breast cancer patients.

    PubMed Central

    Cohen, I; Perel, E; Flex, D; Tepper, R; Altaras, M M; Cordoba, M; Beyth, Y

    1999-01-01

    AIMS: To evaluate whether endometrial pathology is more likely to be diagnosed in gynaecologically symptomatic rather than in gynaecologically asymptomatic postmenopausal breast cancer patients with tamoxifen treatment; and to evaluate the possible influence of various clinical factors on the incidence of endometrial pathology. METHODS: Endometrial histological findings, transvaginal ultrasonographic endometrial thickness, demographic characteristics, health habits, and risk factors for endometrial cancer were compared between 14 gynaecologically symptomatic (group I) and 224 gynaecologically asymptomatic (group II) postmenopausal breast cancer patients with tamoxifen treatment. RESULTS: Overall, 28.6% of the study population had endometrial pathology. The incidence of overall positive endometrial histological findings was significantly higher in group I than in group II (92.9% v 24.6%, p < 0.0001). Atrophic endometrium was more common in group II than in group I (75.3% v 7.1%, p < 0.0001). Most other endometrial pathology was significantly more common in group I than in group II (endometrial hyperplasia, 35.7% v 5.6%, p < 0.0001; endometrial polyps, 35.7% v 13.4%, p < 0.0111; endometrial carcinoma, 21.5% v 0.9%, p < 0.0001). Endometrial pathology appeared considerably later in the gynaecologically asymptomatic patients than in gynaecologically symptomatic patients (p = 0.0002). Vaginal bleeding or spotting occurred exclusively in group I. The incidence of endometrial pathology in the entire study population was consistent with that reported elsewhere, and higher than that reported for healthy postmenopausal women. CONCLUSIONS: Endometrial pathology is more likely to be diagnosed in gynaecologically symptomatic postmenopausal breast cancer patients with tamoxifen treatment, and after a shorter duration of time, than in gynaecologically asymptomatic patients. PMID:10474520

  20. Comparison of WHO and endometrial intraepithelial neoplasia classifications in predicting the presence of coexistent malignancy in endometrial hyperplasia

    PubMed Central

    Usubutun, Alp; Boynukalin, Kubra; Yuce, Kunter

    2010-01-01

    Objective The most commonly used classification system for endometrial hyperplasia is the World Health Organization system which is based on subjective criteria. Another classification system is endometrial intraepithelial neoplasia (EIN) system which uses diagnostic criteria including cytological demarcation, crowded gland architecture, minimum size of 1 mm, and careful exclusion of mimics, and aims to identify a precancer or cancer. The objective of this study was to compare the two classification systems in terms of predicting the presence of a coexistent cancer in surgically treated patients. Methods Biopsy and hysterectomy specimens of 49 women who were subjected to surgery with a preoperative diagnosis of endometrial hyperplasia (EH) according to the WHO system were re-evaluated retrospectively by using EIN system. Results Among the 49 patients, 69.4% had complex atypical EH and 75.5% had EIN at biopsy specimens. EIN was detected in 94.1% of complex atypical EH, and 41.7% of non-atypical EH. Nine women (18.4%) had endometrial cancer. Among women with cancer, all had complex atypical EH or EIN. The rate of coexistent endometrial cancer was 26.5% in women with complex atypical EH and 24.3% in women with EIN. Conclusion Diagnoses of atypical or complex atypical EH and EIN had similar sensitivities and negative predictive values in predicting the coexistent endometrial cancer. Either of these two classification systems may be used safely when an experienced pathologist is available. However, use of the objective EIN system may be preferred whenever possible to prevent diagnostic errors in centers where an experienced pathologist is not available. PMID:20613899

  1. 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.

  2. Visfatin concentrations in patients with endometrial cancer.

    PubMed

    Nergiz Avcioglu, Sümeyra; Altinkaya, Sunduz Ozlem; Küçük, Mert; Yüksel, Hasan; Ömürlü, Imran Kurt; Yanik, Serdar

    2015-03-01

    Visfatin is one of the most recent proteins shown to be highly expressed in adipose tissue. The purpose of this study was to determine visfatin levels in patients with endometrial cancer (EC). A total of 90 patients (46 EC patients and 44 healthy controls) were included in the study. Fasting venous blood samples were collected from all patients. Serum visfatin levels were measured by an enzyme-linked immunosorbent assay (ELISA). The correlation between serum visfatin levels and clinicopathologic variables were determined. Serum visfatin levels were found to be higher in patients with EC (p < 0.001). Visfatin concentrations were positively correlated with age (p = 0.002, r = 0.323), body mass index (BMI) (p = 0.001, r = 0.354), fasting insulin (p = 0.002, r = 0.326), total cholesterol (TC) (p = 0.006, r = 0.285), triglyceride (TG) (p < 0.001, r = 0.364) levels and homeostasis model-resistance index (HOMA-IR) (p = 0.007, r = 0.281) of patients. By using classification and regression trees (C&RT) method, we found that visfatin predicted patients with EC 100% and controls 81.8%. Visfatin was the most important risk factor for occurrence of EC other than, age, BMI, Diabetes Mellitus and other biochemical factors like HDL, LDL, TG, TC. Clearly, there are largely unknown aspects of visfatin pathophysiology in EC and require further study.

  3. Metformin Use and Endometrial Cancer Survival

    PubMed Central

    Nevadunsky, Nicole S.; Van Arsdale, Anne; Strickler, Howard D.; Moadel, Alyson; Kaur, Gurpreet; Frimer, Marina; Conroy, Erin; Goldberg, Gary L.; Einstein, Mark H.

    2013-01-01

    Objective Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancer using metformin have been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC). Methods We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided. Results Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio = 0.54, 95% CI: 0.30–0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed. Conclusion Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC. PMID:24189334

  4. Metformin use and endometrial cancer survival.

    PubMed

    Nevadunsky, Nicole S; Van Arsdale, Anne; Strickler, Howard D; Moadel, Alyson; Kaur, Gurpreet; Frimer, Marina; Conroy, Erin; Goldberg, Gary L; Einstein, Mark H

    2014-01-01

    Impaired glucose tolerance and diabetes are risk factors for the development of uterine cancer. Although greater progression free survival among diabetic patients with ovarian and breast cancers using metformin has been reported, no studies have assessed the association of metformin use with survival in women with endometrial cancer (EC). We conducted a single-institution retrospective cohort study of all patients treated for uterine cancer from January 1999 through December 2009. Demographic, medical, social, and survival data were abstracted from medical records and the national death registry. Overall survival (OS) was estimated using Kaplan-Meier methods. Cox models were utilized for multivariate analysis. All statistical tests were two-sided. Of 985 patients, 114 (12%) had diabetes and were treated with metformin, 136 (14%) were diabetic but did not use metformin, and 735 (74%) had not been diagnosed with diabetes. Greater OS was observed in diabetics with non-endometrioid EC who used metformin than in diabetic cases not using metformin and non-endometrioid EC cases without diabetes (log rank test (p=0.02)). This association remained significant (hazard ratio=0.54, 95% CI: 0.30-0.97, p<0.04) after adjusting for age, clinical stage, grade, chemotherapy treatment, radiation treatment and the presence of hyperlipidemia in multivariate analysis. No association between metformin use and OS in diabetics with endometrioid histology was observed. Diabetic EC patients with non-endometrioid tumors who used metformin had lower risk of death than women with EC who did not use metformin. These data suggest that metformin might be useful as adjuvant therapy for non-endometrioid EC. © 2013. Published by Elsevier Inc. All rights reserved.

  5. Intrauterine devices and endometrial cancer risk: a pooled analysis of the Epidemiology of Endometrial Cancer Consortium.

    PubMed

    Felix, Ashley S; Gaudet, Mia M; La Vecchia, Carlo; Nagle, Christina M; Shu, Xiao Ou; Weiderpass, Elisabete; Adami, Hans Olov; Beresford, Shirley; Bernstein, Leslie; Chen, Chu; Cook, Linda S; De Vivo, Immaculata; Doherty, Jennifer A; Friedenreich, Christine M; Gapstur, Susan M; Hill, Dierdre; Horn-Ross, Pamela L; Lacey, James V; Levi, Fabio; Liang, Xiaolin; Lu, Lingeng; Magliocco, Anthony; McCann, Susan E; Negri, Eva; Olson, Sara H; Palmer, Julie R; Patel, Alpa V; Petruzella, Stacey; Prescott, Jennifer; Risch, Harvey A; Rosenberg, Lynn; Sherman, Mark E; Spurdle, Amanda B; Webb, Penelope M; Wise, Lauren A; Xiang, Yong-Bing; Xu, Wanghong; Yang, Hannah P; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Brinton, Louise A

    2015-03-01

    Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR = 0.81, 95% CI = 0.74-0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR = 0.69, 95% CI = 0.58-0.82), older age at first use (≥ 35 years pooled-OR = 0.53, 95% CI = 0.43-0.67), older age at last use (≥ 45 years pooled-OR = 0.60, 95% CI = 0.50-0.72), longer duration of use (≥ 10 years pooled-OR = 0.61, 95% CI = 0.52-0.71) and recent use (within 1 year of study entry pooled-OR = 0.39, 95% CI = 0.30-0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells) and localized hormonal changes. © 2014 UICC.

  6. Intrauterine devices and endometrial cancer risk: a pooled analysis of the Epidemiology of Endometrial Cancer Consortium

    PubMed Central

    Felix, Ashley S.; Gaudet, Mia M.; La Vecchia, Carlo; Nagle, Christina M.; Ou Shu, Xiao; Weiderpass, Elisabete; Olov Adami, Hans; Beresford, Shirley; Bernstein, Leslie; Chen, Chu; Cook, Linda S.; De Vivo, Immaculata; Doherty, Jennifer A.; Friedenreich, Christine M.; Gapstur, Susan M.; Hill, Dierdre; Horn-Ross, Pamela L.; Lacey, James V.; Levi, Fabio; Liang, Xiaolin; Lu, Lingeng; Magliocco, Anthony; McCann, Susan E.; Negri, Eva; Olson, Sara H.; Palmer, Julie R.; Patel, Alpa V.; Petruzella, Stacey; Prescott, Jennifer; Risch, Harvey A.; Rosenberg, Lynn; Sherman, Mark E.; Spurdle, Amanda B.; Webb, Penelope M.; Wise, Lauren A.; Xiang, Yong-Bing; Xu, Wanghong; Yang, Hannah P.; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Brinton, Louise A.

    2014-01-01

    Intrauterine devices (IUDs), long-acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual-level data from 4 cohort and 14 case-control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled-ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use, and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled-OR=0.81, 95% CI=0.74–0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled-OR=0.69, 95% CI=0.58–0.82), older age at first use (≥35 years pooled-OR=0.53, 95% CI=0.43–0.67), older age at last use (≥45 years pooled-OR=0.60, 95% CI=0.50–0.72), longer duration of use (≥10 years pooled-OR=0.61, 95% CI=0.52–0.71), and recent use (within 1 year of study entry pooled-OR=0.39, 95% CI=0.30–0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells), and localized hormonal changes. PMID:25242594

  7. Metformin targeting autophagy overcomes progesterone resistance in endometrial carcinoma.

    PubMed

    Zhuo, Zhihong; Wang, Aiming; Yu, Huimin

    2016-11-01

    Metformin is the most prescribed anti-diabetic medication worldwide because of its proven efficacy and limited side effects. In this study, the significant anticancer effect of metformin was investigated in both endometrial carcinoma and progesterone-resistant endometrial carcinoma cells. We tested the growth inhibition assay using MTT cell proliferation, cell cycle assay, apoptosis assessment with flow cytometry using propidium iodide and Annexin V, and autophagy protein expression with western blot analysis. Metformin inhibited the growth of cancer cells with different concentrations in a dose- and time-dependent manner. Moreover, the inhibition properties observed as a function of increased concentrations of metformin were markedly augmented when the medication was administered in the progesterone-resistant Ishikawa cells, even with a dose as low as 10 mM. The early and late phases of apoptosis were enhanced in the metformin-treated tumour cells that were analyzed. For the Ishikawa cells, the expression of p-AMPK, LC-3, and beclin1 was upregulated after treatment, whereas the AMPK levels were not modulated. Furthermore, for the Ishikawa-PR cells, the protein levels were similarly upregulated. Finally, we observed that the three proteins showed much more variability in Ishikawa-PR cells than in Ishikawa cells. The application of metformin to target autophagy in endometrial cancer cells provides a new potential treatment for progesterone-resistant endometrial carcinoma.

  8. [Overweight, obesity, diabetes, and hypertension in endometrial cancer].

    PubMed

    Sanz-Chávez, Tania L N; Vilar-Compte, Diana; de Nicola-Delfín, Luigina; Meneses-García, Abelardo

    2013-01-01

    in postmenopausal women, the excess of fat has been associated with an increased risk of endometrial cancer. The aim of the study was to determine the prevalence of overweight, obesity, diabetes and hypertension in patients with endometrial cancer. we collected demographic, clinical, laboratory and histopathological information from the electronic records of patients diagnosed with endometrial cancer in the period from January 2009 to July 2011. Subsequently descriptive analysis of the information was done. a total of 274 records. The average age of patients was 54 years. The 50.4 % were postmenopausal. At the time of diagnosis, 112 cases (48.6 %) were in clinical stage I. Of all patients, 104 (37.9 %) had diabetes mellitus, 122 (44.5 %) hypertension, 194 (72.6 %) were overweight or obese, and 24 cases were registered with the metabolic syndrome. in regards to this diagnosis the results show a higher incidence of overweight and obesity compared with other countries. It is necessary to conduct further studies to assess the relationship of excess fat as a risk factor for endometrial cancer.

  9. Prognostic significance of tumor-associated macrophages in endometrial adenocarcinoma.

    PubMed

    Kübler, Kirsten; Ayub, Tiyasha H; Weber, Sarah K; Zivanovic, Oliver; Abramian, Alina; Keyver-Paik, Mignon-Denise; Mallmann, Michael R; Kaiser, Christina; Serçe, Nuran Bektas; Kuhn, Walther; Rudlowski, Christian

    2014-11-01

    Endometrial adenocarcinoma is one of the most common gynecologic malignancies worldwide and in stages confined to the uterus considered to have an excellent prognosis. However, in advanced or recurrent cases when surgery fails to achieve disease control other treatment options are less effective. Thus, new therapeutic avenues are needed. To provide the rationale for the use of novel agents that target immune checkpoints 163 type I endometrial cancer samples were immunohistochemically screened for the presence of CD163(+) tumor-associated macrophages and Foxp3(+) regulatory T cells. Further, a D2-40-based evaluation of lymph vessel density and lymphovascular space invasion was carried out. Correlation analysis with clinicopathological parameters was performed; Kaplan-Meier curves were generated; multivariate analysis was undertaken as appropriate. A substantial amount of tumor-associated macrophages and regulatory T cells was detected in all specimens characterizing endometrial cancer as an immunogenic tumor. However, only the increased infiltration of tumor-associated macrophages was proportionally associated with advanced FIGO stages, high tumor grade, increased lymph vessel density, lymphovascular space invasion and lymph node metastasis. Thus, the presence of tumor-associated macrophages indicates aggressive tumor behavior and appeared to be an independent prognostic factor for recurrence-free survival. Our results make future therapeutic approaches that target tumor-associated macrophages reasonable to improve the outcome of women with advanced or recurrent endometrial adenocarcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Multivariate survival analysis of the patients with recurrent endometrial cancer

    PubMed Central

    Odagiri, Tetsuji; Hosaka, Masayoshi; Mitamura, Takashi; Konno, Yousuke; Kato, Tatsuya; Kobayashi, Noriko; Sudo, Satoko; Takeda, Mahito; Kaneuchi, Masanori; Sakuragi, Noriaki

    2011-01-01

    Objective Few studies on the prognosticators of the patients with recurrent endometrial cancer after relapse have been reported in the literature. The aim of this study was to determine the prognosticators after relapse in patients with recurrent endometrial cancer who underwent primary complete cytoreductive surgery and adjuvant chemotherapy. Methods Thirty-five patients with recurrent endometrial cancer were included in this retrospective analysis. The prognostic significance of several clinicopathological factors including histologic type, risk for recurrence, time to relapse after primary surgery, number of relapse sites, site of relapse, treatment modality, and complete resection of recurrent tumors were evaluated. Survival analyses were performed by Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis. Results Among the clinicopathological factors analyzed, histologic type (p=0.04), time to relapse after primary surgery (p=0.03), and the number of relapse sites (p=0.03) were significantly related to survival after relapse. Multivariate analysis revealed that time to relapse after primary surgery (hazard ratio, 6.8; p=0.004) and the number of relapse sites (hazard ratio, 11.1; p=0.002) were independent prognostic factors for survival after relapse. Survival after relapse could be stratified into three groups by the combination of two independent prognostic factors. Conclusion We conclude that time to relapse after primary surgery, and the number of relapse sites were independent prognostic factors for survival after relapse in patients with recurrent endometrial cancer. PMID:21607089

  11. Small non-coding RNA deregulation in endometrial carcinogenesis

    PubMed Central

    Ravo, Maria; Cordella, Angela; Rinaldi, Antonio; Bruno, Giuseppina; Alexandrova, Elena; Saggese, Pasquale; Nassa, Giovanni; Giurato, Giorgio; Tarallo, Roberta; Marchese, Giovanna; Rizzo, Francesca; Stellato, Claudia; Biancardi, Rossella; Troisi, Jacopo; Di Spiezio Sardo, Attilio; Zullo, Fulvio; Weisz, Alessandro; Guida, Maurizio

    2015-01-01

    Small non-coding RNAs (sncRNAs) represent a heterogeneous group of <200nt-long transcripts comprising microRNAs, PIWI-interacting RNAs (piRNAs) and small-nucleolar-RNAs (snoRNAs) involved in physiological and pathological processes such as carcinogenesis and tumor progression. Aberrant sncRNA expression in cancer has been associated with specific clinical phenotypes, grading, staging, metastases development and resistance to therapy. Aim of the present work is to study the role of sncRNAs in endometrial carcinogenesis. Changes in sncRNA expression were identified by high-throughput genomic analysis of paired normal, hyperplastic and cancerous endometrial tissues obtained by endometrial biopsies (n = 10). Using smallRNA sequencing and microarrays we identified significant differences in sncRNA expression pattern between normal, hyperplastic and neoplastic endometrium. This led to the definition of a sncRNA signature (129 microRNAs, 2 of which not previously described, 10 piRNAs and 3 snoRNAs) of neoplastic transformation. Functional bioinformatics analysis identified as downstream targets multiple signaling pathways potentially involved in the hyperplastic and neoplastic tissue responses, including Wnt/β-catenin, and ERK/MAPK and TGF-β-Signaling. Considering the regulatory role of sncRNAs, this newly identified sncRNA signature is likely to reflect the events leading to endometrial cancer, which can be exploited to dissect the carcinogenic process including novel biomarkers for early and non-invasive diagnosis of these tumors. PMID:25686835

  12. Conceiving THz endometrial ablation: feasibility, requirements and technical challenges.

    PubMed

    Neelakanta, Perambur S; Sharma, Bharti

    2013-07-01

    Shallow-ablation of endometrial lining using microwaves has been traditionally indicated as a minimally invasive treatment option for dysfunctional uterine bleeding (DUB). Known as microwave endometrial ablation (MEA), relevant procedure is used as an alternative to hysterectomy considering its safety, simplicity and effectiveness. In lieu of the prevailing MEA techniques, it is attempted in this study to foresee the possibility of conceiving an alternative and a newer option on endometrial ablation using mm-wave/THz frequencies. Commensurate with this motivated impetus, objectively considered are merits and design issues of using electromagnetic (EM) spectrum of mm-wave/THz region toward optimal conversion of EM energy into a thermal ablative source so that, the basal layer of endometrium can be effectively destroyed in surgical contexts as necessary. Hence, the feasibility of designing appropriate TEA applicators for controlled and safe procedures so as to ablate just the unwanted tissues within a localized zone of energy field is addressed. Lastly, a quantitative analysis on the interaction of THz EM-energy versus the lossy dielectric characteristics of endometrial medium is indicated to model the underlying (THz-energy)-to-(thermal energy) transduction. Relevant prospects of conceiving TEA and the associated pros and cons are identified specific to the prospects of feasibility, requirement considerations and technical challenges.

  13. Molecular Biology and Prevention of Endometrial Cancer. Addendum

    DTIC Science & Technology

    2008-07-01

    gain insight into the biologic mechanism underlying the chemopreventive effect of the oral contraceptive pill (OCP). Project 1: Objectives completed...oral contraceptive pill and hormone replacement therapy on reproductive organs. This objective has been completed and the results were submitted...protective effect of oral contraceptive (OC) therapy. Methods: 1) Oligonucleotide microarray analysis was performed on a panel of endometrial cancers

  14. Primary pulmonary carcinoid tumor with metastasis to endometrial polyp

    PubMed Central

    Momeni, Mazdak; Kolev, Valentin; Costin, Dan; Mizrachi, Howard H.; Chuang, Linus; Warner, Richard R.P.; Gretz, Herbert F.

    2012-01-01

    INTRODUCTION A carcinoid tumor occurring in the endometrium has been documented in the literature, but there is no report in regard to carcinoid tumor metastasis to endometrium. PRESENTATION OF CASE We report a case of a malignant carcinoid metastasis to an endometrial polyp. Patient underwent hysteroscopy, and polypectomy. The pathology demonstrated an endometrial polyp containing a 4 mm x 5 mm nodule of metastatic carcinoid tumor, consistent with metastasis from patient's known pulmonary carcinoid. The tumor was morphologically similar to the tumors of the right lung, with similar immune-profile. DISCUSSION This patient presented with a suspicious pelvic ultrasound. Due to her age, the first priority was to exclude uterine cancer. The endometrial polyp, which was found, had a small focus of metastatic carcinoid tumor. To the best of our knowledge, this finding has not been previously recorded in the literature. Our patient also had a history of metastatic carcinoid tumor to breast. This finding is also very uncommon. CONCLUSION This is the first case in the literature described a malignant carcinoid metastasis to an endometrial polyp. PMID:23127865

  15. Long-term survival of endometrioid endometrial cancer patients

    PubMed Central

    Pluta, Piotr; Piekarski, Janusz; Spych, Michał; Hendzel, Katarzyna; Topczewska-Tylinska, Katarzyna; Nejc, Dariusz; Bibik, Robert; Korczyński, Jerzy; Ciałkowska-Rysz, Aleksandra

    2010-01-01

    Introduction To establish risk factors for onset and progression of endometrioid endometrial cancer still remains the aim of scientists. The aim of the study was to determine disease-free survival (DFS) and overall survival (OS) in women with endometrioid endometrial cancer. Material and methods A retrospective review of 142 patients with endometrioid endometrial cancer after surgery treated with adjuvant radiotherapy and/or chemotherapy in the Regional Cancer Centre in Lodz between 2002 and 2004 was performed. Clinical and pathological data were correlated with clinical outcome and survival. Results In 3 patients (2.1%) clinical progression was diagnosed during the treatment. In 23 patients (16.7%) after primary remission, relapse was diagnosed 2-56 months after treatment. DFS and OS were 81.7% and 83.1% respectively. Better DFS significantly correlated with larger number of pregnancies (> 1), stage I of the disease and optimal surgery. Lower stage of disease, pelvic lymph node dissection, optimal surgery and depth of myometrial infiltration ≤ 50% were independent prognostic factors for better OS. Conclusions The results of our study provided significant evidence that early detection of endometrioid endometrial cancer enables optimal surgery. It reduces the indications for adjuvant therapy in stage I of the disease, and makes the prognosis significantly better. Other clinical and pathological factors such as numerous pregnancies, pelvic lymphadenectomy, and depth of myometrial infiltration, although important, are of less significance. Further prospective, randomized studies are necessary to prove the role of these factors. PMID:22427770

  16. Treatment of endometrial hyperplasia with levonorgestrel releasing intrauterine devices.

    PubMed

    Perino, A; Quartararo, P; Catinella, E; Genova, G; Cittadini, E

    1987-01-01

    The effectiveness of a new levo-norgestrel releasing intrauterine device is assessed in fourteen patients with histologically confirmed hyperplastic lesions of the endometrial mucosa. The morphologic response of the hyperplastic endometria to the action of the levo-norgestrel in this study explains the regression of the cases so treated.

  17. Utility of immunohistochemistry in predicting microsatellite instability in endometrial carcinoma.

    PubMed

    Modica, Ippolito; Soslow, Robert A; Black, Destin; Tornos, Carmen; Kauff, Noah; Shia, Jinru

    2007-05-01

    Identification of the microsatellite instability (MSI) phenotype in endometrial carcinoma is important given that such tumors are the most common noncolorectal tumors to occur in hereditary nonpolyposis colorectal cancer syndrome, and may bear prognostic relevance. The objective of this study was to assess the utility of immunohistochemistry (IHC), a simple and fast technique, in detecting MSI in endometrial carcinoma. The study subjects consisted of 90 endometrial carcinoma patients with equal representation of MSI-high (MSI-H) and non-MSI-H tumors. MSI was tested using the standard polymerase chain reaction-based method and the 5 NCI-recommended markers. Overall, IHC with MLH1 and MSH2 antibodies detected 69% of MSI-H tumors with a specificity of 100%. Adding PMS2 and MSH6 to the antibody panel increased the sensitivity to 91% but decreased the specificity to 83%. The most common IHC abnormality in MSI tumors was concurrent loss of MLH1/PMS2. Assessment of staining was straightforward in most cases but not in all. Staining inadequacies existed. Five stains (4 MLH1 and 1 MSH6) were not interpretable because of the lack of any internal positive control. Two percent to 10% of the cases (depending on the antibody assessed) had only focal weak staining; the highest frequency (10%) occurred with MLH1 antibody. PMS2 staining detected 7 MLH1-staining present MSI-H cases, thus partly accounting for the increased sensitivity with the 4-antibody panel. MSH6 staining identified 9 cases with loss of MSH6 alone, 6 of 9 were non-MSI-H, thus partly accounting for the decreased specificity with the 4-antibody panel. In conclusion, our results suggest that IHC is useful in detecting MSI in endometrial carcinoma. Although IHC has a lower sensitivity with more apparent staining inadequacies in detecting MSI in endometrial carcinoma than it does in colorectal carcinoma, its use in endometrial carcinoma may be an important adjunct when screening for hereditary cases. In the future, as

  18. Hormonal therapy in advanced or recurrent endometrial cancer

    PubMed Central

    Kokka, Fani; Brockbank, Elly; Oram, David; Gallagher, Chris; Bryant, Andrew

    2014-01-01

    Background Endometrial cancer is a cancer of the lining of the womb and worldwide is the seventh most common cancer in women. Treatment with hormones is thought to be beneficial in patients with endometrial cancer. Objectives To assess the indications, effectiveness and safety of hormone therapy for advanced or recurrent epithelial endometrial cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE up to May 2009 and and CENTRAL (Issue 2, 2009). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies, and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that studied hormonal therapy in adult women diagnosed with advanced or recurrent endometrial cancer. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Comparisons were restricted to single-trial analyses so we did not synthesise data in meta-analyses. Main results We found six trials (542 participants) that met our inclusion criteria. These trials assessed the effectiveness of hormonal therapy in women with advanced or recurrent endometrial cancer as a single agent, as part of combination therapy and as low versus high dose. All comparisons were restricted to single-trial analyses, where we found no evidence that hormonal therapy as a single agent or as a combination treatment prolonged overall or five-year disease-free survival of women with advanced or recurrent endometrial cancer. However, low-dose hormonal therapy may have had a benefit in terms of overall and progression-free survival (PFS) compared to high-dose hormonal therapy (HR 1.31, 95% CI 1.04 to 1.66 and HR 1.35, 95% CI 1.07 to 1.71 for overall and PFS, respectively). Authors’ conclusions We found insufficient evidence that hormonal treatment in any form, dose or as part of combination therapy improves the survival of patients with advanced or

  19. Accuracy of endometrial sampling compared to conventional dilatation and curettage in women with abnormal uterine bleeding.

    PubMed

    Abdelazim, Ibrahim A; Abdelrazak, Khaled M; Elbiaa, Assem A M; Al-Kadi, Mohamed; Yehia, Amr H

    2015-05-01

    To compare the diagnostic accuracy of brush endometrial sampling with conventional dilatation and curettage in women with abnormal uterine bleeding. Two hundred and twenty (220) women with abnormal uterine bleeding were included in this comparative study; endometrial sampling was done before cervical dilatation using Tao Bruch followed by conventional dilatation and curettage (D&C). The histopathology report of the Tao Bruch samples was compared with that of the D&C samples and the D&C results were considered as the gold standard. 100% of samples obtained by conventional D&C, while 98.2% of the samples obtained by Tao Brush were adequate for histopathology examination. In this study; Tao Brush had 100% sensitivity, 100% specificity, 100% predictive values and accuracy for diagnosing endometrial hyperplasia, endometrial carcinoma, proliferative and secretory endometrium, also, it had 86.7% sensitivity, 100% specificity, 100% positive predictive value (PPV) and 99% negative predictive value (NPV) and accuracy for diagnosing endometritis (no significant difference compared to conventional D&C), while, it had 77.8% sensitivity, 100% specificity, 100% PPV and 99% NPV and accuracy for diagnosing endometrial polyps (no significant difference compared to conventional D&C) CONCLUSION: Endometrial sampling using endometrial brush cytology (EBC) is safe, accurate, cost-effective outpatient procedure, avoids general anesthesia with high sensitivity and specificity for detection of endometrial hyperplasia and endometrial carcinoma. EBC could be used as complementary diagnostic tool when hysteroscopic biopsies or other blinded procedures for endometrial sampling are unwanted or not available.

  20. Evaluation of endometrial cytology: cytohistological correlations in 1,441 cancer patients.

    PubMed

    Fujiwara, Hiroyuki; Takahashi, Yoshifumi; Takano, Masashi; Miyamoto, Morikazu; Nakamura, Kazuto; Kaneta, Yoshibumi; Hanaoka, Tatsuya; Ohwada, Michitaka; Sakamoto, Takanori; Hirakawa, Takashi; Fujiwara, Keiichi; Suzuki, Mitsuaki

    2015-01-01

    Endometrial cytology by direct intrauterine sampling is the most common test for an initial evaluation of the endometrium in Japan. However, its diagnostic value for endometrial cancer remains unknown. Here, we assess the correlation between cytopathology and histopathology to evaluate the diagnostic value of cytology for endometrial cancer. Patients with histologically confirmed endometrial cancer and controls with a normal endometrium confirmed by hysterectomy had all undergone preoperative endometrial cytology between 2001 and 2010 at our eight institutions and were retrospectively analyzed. The cytological results were compared by clinical stage, histological type, differentiation, and sampling instrument. We analyzed 1,441 endometrial cancer and 1,361 control cases. Endometrial cytology detected cancer in 1,279 (916 positive and 363 suspicious) cases with a sensitivity (positive plus suspicious cases) of 88.8% and a specificity of 98.5%. The positive rate was high in advanced-stage, nonendometrioid, and undifferentiated cases, but there was no significant difference in sensitivity between these clinical conditions. Endometrial cytology shows a relatively high sensitivity and specificity for endometrial cancer, and neither statistical measure is significantly affected by clinical stage, histological type, differentiation, sample numbers, or sampling instrument. These findings form a superior dataset for evaluating the efficacy of endometrial cytology. © 2014 S. Karger AG, Basel.

  1. Body Mass Index Is Positively Associated with Endometrial Cancer in Chinese Women, Especially Prior to Menopause.

    PubMed

    Gao, Yifei; Dai, Xujing; Chen, Limei; Lee, Arier C; Tong, Mancy; Wise, Michelle; Chen, Qi

    2016-01-01

    Obesity is a well-known risk factor for developing endometrial cancer. However, the incidence and survival rate of endometrial cancer are associated with ethnicity and geographical area. In addition, whether menopausal status is associated with developing endometrial cancer in obese women and whether obesity is associated with subtypes of endometrial cancer have not been fully investigated. Here, we investigated the effect of BMI on developing endometrial cancer in Chinese women taking into account menopausal status and cancer subtypes. Data on 1,127 women with endometrial cancer including body mass index (BMI), age at diagnosis, parity, menopausal status and cancer subtype were collected from the largest obstetrics & gynaecology hospital in China and analysed. After adjusting for age and parity, the odds for developing endometrial cancer in overweight or obese perimenopausal women was significantly higher than that in women with normal weight (OR=2.6 with 95%CI:1.9-3.5, and OR=3.5 with 95%CI: 2.2-5.4, respectively). The odds of developing endometrial cancer in overweight postmenopausal women were significantly higher than that in women who were normal weight (OR=2.4 with 95%CI: 1.8-3.1), however this was not the case for obese postmenopausal women. We further found that BMI, menopausal status, age and parity were not associated with subtypes of endometrial cancer. Our data demonstrate that obesity is positively associated with the incidence of developing endometrial cancer in Chinese women, with more significant effects in perimenopausal women.

  2. Long-term impact of preeclampsia on maternal endometrial cancer risk.

    PubMed

    Hallum, Sara; Pinborg, Anja; Kamper-Jørgensen, Mads

    2016-03-29

    Endometrial cancer is mainly dependent on oestrogen exposure. Preeclampsia has shown to reduce oestrogen levels hence preeclampsia may affect later endometrial cancer risk. We conducted a case-control study of 523 Danish women with endometrial cancer and 52 299controls during 1978-2010. The association between preeclampsia and later endometrial cancer was evaluated overall and according to preeclampsia onset and type of endometrial cancer in conditional logistic regression models. We observed no overall association between preeclampsia and endometrial cancer risk (OR=1.11 (95% CI 0.68-1.81)). This was true for all endometrial cancer subtypes. In an analysis of preeclampsia onset, however, we report a markedly increased risk of endometrial cancer following early-onset preeclampsia (OR=2.64 (95% CI 1.29-5.38)). Although we report no obvious association between preeclampsia and endometrial cancer, studying the subset of early-onset preeclampsia may prove fruitful in further understanding the aetiology of endometrial cancer.

  3. Fat accumulation in adipose tissues as a risk factor for the development of endometrial cancer.

    PubMed

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

    2011-07-01

    Fat accumulation in adipose tissues is a risk factor for the development of human cancers. However, there are no studies describing the fat accumulation in adipose tissue or its distribution in human endometrial cancer. We first examined fat accumulation in adipose tissues separately on CT images of 122 patients with endometrial cancer, and investigated the correlation of these findings with various histological types of endometrial cancers. Fat accumulation in adipose tissues [subcutaneous fat area (SFA) and/or visceral fat areas (VFA)] was strongly correlated with the group of obesity-related biological parameters (weight, body mass index (BMI), waist and body surface area (BSA)) in endometrial cancer. The incidence of type I endometrial cancer was more closely correlated with an increase in obesity-related parameters such as weight (p=0.011), BMI (p=0.006), waist circumference (p=0.038), BSA (p=0.016), SFA (p=0.005), total fat area (TFA) (p=0.006) and total cholesterol (T.Cho) (P=0.010) than type II endometrial cancer. In particular, the SFA was most strongly correlated with obesity-related biological parameters of type I endometrial cancer. The present findings indicate that type I endometrial cancer has a statistically significant increase in obesity-related biological parameters than type II endometrial cancer. We propose that the subcutaneous fat accumulation in adipose tissue is a strong risk factor for developing type I endometrial cancer.

  4. The role of vaginal cuff brachytherapy in endometrial cancer.

    PubMed

    Harkenrider, Matthew M; Block, Alec M; Siddiqui, Zaid A; Small, William

    2015-02-01

    The purpose of this article is to review the data, rationale, and recommendations of vaginal brachytherapy (VBT) in the post-operative treatment of endometrial cancer patients. The authors performed a thorough review of the medical literature regarding the use of adjuvant VBT in the treatment of endometrial cancer. Relevant data are presented in this review. Additionally, personal and institutional practices from the authors are incorporated where relevant. VBT for the adjuvant treatment of early stage endometrial cancer patients results in a low rate of recurrence (0-3.1%) with very low rates of toxicity. PORTEC-2 supports the use of adjuvant VBT versus external beam radiotherapy specifically for high-intermediate risk endometrial cancer patients. VBT has low rates of acute and chronic gastrointestinal and genitourinary toxicity and very low rates of second primary malignancy. The primary toxicity of VBT is vaginal atrophy and stenosis with controversy regarding the use of vaginal dilators for prevention. Data support that patients prefer to be involved in the decision making process for their adjuvant therapy, and patients have a lower minimal desired benefit of adjuvant VBT than do physicians. Guidelines exist from the American Brachytherapy Society and American Society of Radiation Oncology with support from the Society for Gynecologic Oncologists regarding the use of adjuvant VBT. VBT decreases the risk of recurrence with minimal toxicity in the adjuvant treatment of endometrial cancer. Adjuvant therapy should be discussed in a multi-disciplinary setting with detailed counseling of the risks and benefits with the patient so that she ultimately makes an informed decision regarding her adjuvant therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Soy Intake Is Associated With Lower Endometrial Cancer Risk

    PubMed Central

    Zhang, Guo-Qiang; Chen, Jin-Liang; Liu, Qin; Zhang, Yong; Zeng, Huan; Zhao, Yong

    2015-01-01

    Abstract Epidemiologic studies reporting the effect of soy intake on endometrial cancer risk conveyed conflicting results. We systematically reviewed the literature to investigate whether there was an inverse relation between dietary soy intake and endometrial cancer risk. PubMed, EMBASE, the Cochrane Library, and 4 main Chinese literature databases were searched from their inception to August 25, 2015 for both case–control studies and cohort studies that assessed the effect of soy intake on endometrial cancer risk. Study-specific most-adjusted odds ratios (ORs) or relative risks (RRs) were combined by using fixed-effects or random-effects model to calculate pooled risk estimates (REs). A total of 10 epidemiologic studies were included in this meta-analysis, including 8 case–control studies and 2 prospective cohort studies. Dietary soy intake was inversely associated with endometrial cancer risk with an overall RE of 0.81 (95% CI: 0.72, 0.91). In subgroup analyses, a statistically significant protective effect of soy intake was found for unfermented soy food (RE: 0.81, 95% CI: 0.67, 0.97), postmenopausal women (RE: 0.76, 95% CI: 0.61, 0.95), and Asian (RE: 0.79, 95% CI: 0.66, 0.95) and non-Asian population (RE: 0.83, 95% CI: 0.71, 0.96). Current evidence indicates that soy food intake is associated with lower endometrial cancer risk. Further larger cohort studies are warranted to fully clarify such an association. PMID:26683956

  6. Influence of VEGFR and LHCGR on endometrial adenocarcinoma

    PubMed Central

    Kölbl, Alexandra C.; Birk, Amelie E.; Kuhn, Christina; Jeschke, Udo; Andergassen, Ulrich

    2016-01-01

    Endometrial adenocarcinoma is a common gynecological malignancy that is usually treated by surgical resection followed by radiation. However, the frequency of remote metastasis is high. The present study aimed to investigate whether patients with endometrial adenocarcinoma exhibited a positive response to treatment with a gonadotropin-releasing hormone analogue or inhibitors of neoangiogenesis, which are applied for the treatment of other malignancies. Immunohistochemical analyses were performed using 203 paraffin-embedded tissue samples of endometrial adenocarcinomas from patients who had undergone surgery at the Department of Obstetrics and Gynecology of the Ludwig Maximilians University of Munich, Germany. The tissues were incubated with antibodies against luteinizing hormone/choriogonadotropin receptor (LHCGR) and vascular endothelial growth factor receptor 2 (VEGFR2), and evaluated by bright field microscopy. The staining was categorized according to the Immune-Reactive-Score (IRS). The IRS scores were then statistically associated with various tumor traits, including tumor size, lymph node status, metastasis, grade, expression of steroid hormone receptors and patient survival. There was a significant association between VEGFR2 expression and tumor grading and estrogen receptor-α (ERα). For LHCGR, a correlation was observed with ERα and progesterone receptor (PR). No correlations were identified between VEGFR2 or LHCGR expression and the other examined tumor traits or patient survival. The associations between VEGFR2 and ERα, and between LHCGR and ERα or PR, may be explained by the interaction of these signal transduction molecules in the regulation of cellular growth and differentiation. These mechanisms also have an important role in the formation of remote metastases, which is the main cause for tumor-associated mortality. The results of the present study suggested that patients with endometrial adenocarcinoma may benefit from treatment with inhibitors

  7. Endometrial safety of hormone replacement therapy: review of literature.

    PubMed

    Van Gorp, Toon; Neven, Patrick

    2002-06-25

    Unopposed estrogens for treating menopausal symptoms were extensively used when epidemiological findings associated them with an increased endometrial cancer risk. Adding progestogens reverse this side effect efficiently but patient, dose, type and especially time during which the progestogen is administered are important. Long-term uterine safety of the long cycle HRT with administration of the progestogen every 3 months remains unclear. Because regular bleeding lowers compliance, continuous combined estrogen-progestogen treatment has become popular. Many different regimens are now available using oral, transdermal, subcutaneous, intravaginal or intra-uterine application of the estrogen and/or progestogen. Available but inadequate studies seem to point towards a slightly decreased endometrial cancer risk with continuous combined preparations compared with non-HRT-users and an increased risk with long-term oral but not vaginal treatment with low-potency estrogen formulations such as estriol. Newer compounds for menopausal health such as tibolone and raloxifene seem to be safe. As for any women with abnormal vaginal bleeding, those on HRT must have an intra-uterine evaluation. Transvaginal ultrasound (TVU) is very accurate in predicting a normal uterine cavity but inaccurate in predicting endometrial pathology because of a low specificity and positive predictive value of a thick echogenic endometrium. In all such cases a three-dimensional visualisation of intra-uterine lesions is more accurate. Periodic examination with TVU and/or endometrial biopsy of HRT exposed endometrium in asymptomatic women is not cost-effective. The available limited data on the use of HRT in hysterectomised women for early stage endometrial cancer show little evidence in terms of recurrence.

  8. Lymphadenectomy for endometrial cancer: is paraaortic lymphadenectomy necessary?

    PubMed

    Yaegashi, Nobuo; Ito, Kiyoshi; Niikura, Hitoshi

    2007-06-01

    Total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO) have been performed as a standard surgical treatment for endometrial cancer. Many studies have reported on issues such as whether retroperitoneal lymphadenectomy should also be performed with TAH+BSO, to what extent lymphadenectomy should be performed when TAH+BSO is performed, and in what type of patients should lymphadenectomy be performed. These issues have been actively discussed, but there has not been any consensus. In this review article, the benefits of retroperitoneal lymphadenectomy in the initial surgical treatment for endometrial cancer will be discussed in terms of patients with pelvic lymphadenectomy and those with paraaortic (PA) lymphadenectomy. From the previous data, the establishment of TAH+BSO plus pelvic lymphadenectomy as the standard surgical treatment for endometrial cancer is thought to be reasonable. In this situation, is there benefit in performing PA lymphadenectomy? A discussion will be provided by separating the diagnostic significance from the therapeutic significance of this treatment. At present, there are no established treatments for PA-lymph node-positive patients that can be recommended more than the adjuvant therapies that are already performed at various institutions. A scientific basis that clearly indicates the therapeutic effect of PA lymphadenectomy does not exist at the present time. Despite performing thorough PA lymphadenectomy, the route of progression to extrauterine sites cannot be completely controlled. The standard surgical procedure for endometrial cancer is TAH+BSO+pelvic lymphadenectomy, which is considered necessary and sufficient. At present, the addition of PA lymphadenectomy for endometrial cancer can be regarded as only an investigated protocol.

  9. Statin use and survival in elderly patients with endometrial cancer.

    PubMed

    Yoon, Lara S; Goodman, Marc T; Rimel, B J; Jeon, Christie Y

    2015-05-01

    Endometrial cancer is the most common gynecologic cancer in the United States. Statins have demonstrated anti-cancer effects in other tumor types, such as the breast and lung cancers. The objective of our study was to determine the association between statin use and endometrial cancer survival in a nationally-representative elderly population with endometrial cancer in the U.S. We employed the linked Surveillance, Epidemiology and End Results registries and Medicare claims files to collect data from 2987 patients who were diagnosed with endometrial cancer between 2007 and 2009 and who received a hysterectomy. The association between statin use and overall survival was examined using Cox regression models adjusting for follow-up time, age, race, neighborhood income, cancer stage, tumor grade, hysterectomy type, chemotherapy, radiation, impaired glucose tolerance, obesity, dyslipidemia and diabetes. The mortality rate was lower in statin users compared to non-users for both type I (4.6 vs. 5.7 deaths/100 person-years, p=0.08) and type II (11.2 vs. 16.5 deaths/100 person-years, p=0.01) cancer types. However, after adjustment for the time from surgery to statin use and confounding, statin use after a hysterectomy was not significantly associated with a reduction in hazard of death for both type I (hazard ratio [HR] 0.92, 95%CI 0.70,1.2) and type II (HR=0.92, 95%CI 0.65, 1.29, p=0.62) endometrial cancer patients. Accounting for all confounders and biases considered, statin use on or after a hysterectomy was not associated with survival in those with type I or type II disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Endometrial cancer and meat consumption: a case-cohort study.

    PubMed

    van Lonkhuijzen, Luc; Kirsh, Victoria A; Kreiger, Nancy; Rohan, Thomas E

    2011-07-01

    Diet plays an important role in the etiology of certain cancers, but there is limited evidence with regard to the association between diet and risk of endometrial cancer. Few prospective studies have investigated meat intake as a potential determinant of endometrial cancer risk. The objective of this study was to examine the association between endometrial cancer risk and total meat, red meat, processed meat, fish, and poultry intake. We conducted a case-cohort analysis within the Canadian Study of Diet, Lifestyle, and Health, a prospective cohort of 73 909 adults (39 614 women). Participants were recruited from 1992 to 1999, predominantly from three Canadian universities. We conducted a linkage with the Ontario Cancer Registry for the years 1992-2007 for the female cohort members, who resided in Ontario at the time of enrollment (n=26 024), to yield data on cancer incidence. The analytic sample was comprised of 107 incident cases and 1830 subcohort members, the latter being an age-stratified sample of the full cohort. A nonsignificant increase in the risk of endometrial cancer was associated with increased consumption of red meat [hazard ratio (HR)=1.62, 95% confidence intervals (CI)=0.86-3.08, for high vs. low intake; P trend=0.13)], processed meat (HR=1.45, 95% CI=0.80-2.61, for high vs. low intake; P trend=0.058), and all meat combined (HR=1.50, 95% CI=0.78-2.89, for high vs. low intake; P trend=0.14). No clear patterns were noted for poultry or fish. The results of this study, although based on a limited number of cases, suggest that relatively high meat intake may be associated with increased risk of endometrial cancer.

  11. Endometrial metaplasias and reactive changes: a spectrum of altered differentiation.

    PubMed

    Nicolae, Alina; Preda, Ovidiu; Nogales, Francisco F

    2011-02-01

    Endometrial metaplasias and changes (EMCs) are conditions frequently overlooked and misdiagnosed. The aim of this review is to update current issues and provide a classification with a practical clinicopathological approach. Hormonal or irritative stimuli are the main inducing factors of EMCs, although some metaplasias have a mutational origin. EMCs vary from reactive, degenerative lesions to those able to associate with malignancy or those having a preneoplastic potential. The most common types of EMCs are ciliated tubal metaplasia (CTM) and mucinous metaplasia (MM), which occur in simple and complex glands, and possibly these architectural changes hold the same prognostic significance as they do in hyperplastic endometrioid lesions. Immunohistochemically, CTM is positive for LhS28, bcl-2, PAX2 and p16(INK4A). Complex CTM is likely to be a precursor of ciliated endometrioid-type carcinomas. MMs should be evaluated architecturally, taking into account that their atypicality is minimal. The differentiation between complex MM and mucinous carcinoma may be extremely difficult. Surface complex, papillary MM in endometrial polyps can be considered as benign. Intestinal-type endometrial MM is rare and its presence should prompt further investigation of associated lesions in the endocervix. Endometrial squamous metaplasia (ESS) is often linked to chronic irritative situations. It should be differentiated from secondary involvement by a human papilomavirus-related cervical lesion. Morular metaplasia is a mutational phenomenon with a distinct phenotype that helps to differentiate it from ESS. Morules are benign, hormonally inert structures that are often markers of complex endometrioid glandular architecture, and they are associated with an attenuated malignancy. Endometrial reactive changes are commonly associated with desquamation or hormonal imbalance. The frequent, p16(INK4A) positive, benign surface papillary syncytial change may be misdiagnosed, in some cases, as

  12. Association Between Statin Use and Endometrial Cancer Survival.

    PubMed

    Nevadunsky, Nicole S; Van Arsdale, Anne; Strickler, Howard D; Spoozak, Lori A; Moadel, Alyson; Kaur, Gurpreet; Girda, Eugenia; Goldberg, Gary L; Einstein, Mark H

    2015-07-01

    To evaluate the association of 3 hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) use and concordant polypharmacy with disease-specific survival from endometrial cancer. A retrospective cohort study was conducted of 985 endometrial cancer cases treated from January 1999 through December 2009 at a single institution. Disease-specific survival was estimated by Kaplan-Meier analyses. A Cox proportional hazards model was used to study factors associated with survival. All statistical tests were two-sided and performed using Stata. At the time of analysis, 230 patients (22% of evaluable patients) died of disease and median follow-up was 3.28 years. Disease-specific survival was greater (179/220 [81%]) for women with endometrial cancer taking statin therapy at the time of diagnosis and staging compared with women not using statins (423/570 [74%]) (log rank test, P=.03). This association persisted for the subgroup of patients with nonendometrioid endometrial tumors who were statin users (59/87 [68%]) compared with nonusers (93/193 [43%]) (log rank test, P=.02). The relationship remained significant (hazard ratio 0.63, 95% confidence interval [CI] 0.40-0.99) after adjusting for age, clinical stage, radiation, and other factors. Further evaluation of polypharmacy showed an association between concurrent statin and aspirin use with an especially low disease-specific mortality (hazard ratio 0.25, 95% CI 0.09-0.70) relative to those who used neither. Statin and aspirin use was associated with improved survival from nonendometrioid endometrial cancer.

  13. The incidence rates of endometrial hyperplasia and endometrial cancer: a four-year population-based study

    PubMed Central

    2016-01-01

    Introduction The aim of this study was to determine the incidence rates of endometrial hyperplasia (EH) and endometrial cancer (EC) in the Republic of Korea using national insurance claim data generated from 2009 to 2012. Materials and Methods Data that were generated from 2009 to 2012 were sourced from the Korean Health Insurance Review and Assessment Service-National Inpatients Sample database. The data from women who were assigned diagnosis codes representing EH or EC within 1 month of being assigned codes that corresponded to procedures that included endometrial biopsies and several types of gynecologic surgeries to obtain endometrial pathology samples, were selected for analysis. Results Data from 2,477,424 women were entered into the database between 2009 and 2012, and the data from 1,868 women with EH and 868 women with EC were extracted for analysis. The mean ages of the patients were 44.1 ± 0.4 years for those with EH and 52.7 ± 0.6 years for those with EC. The EH and EC incidence rates were 37 per 100,000 woman-years and 8 per 100,000 woman-years, respectively. The EH and EC incidence rates peaked when the women were in their late forties and fifties, respectively. Conclusions The EH and EC incidence rates determined in this study were somewhat lower than those determined from previous studies. Further studies are required that adjust the data for race, menopausal hormone therapy, and obesity. PMID:27635340

  14. Evaluation of two endometriosis models by transplantation of human endometrial tissue fragments and human endometrial mesenchymal cells

    PubMed Central

    Jafarabadi, Mina; Salehnia, Mojdeh; Sadafi, Rana

    2017-01-01

    Background: The animal models of endometriosis could be a valuable alternative tool for clarifying the etiology of endometriosis. Objective: In this study two endometriosis models at the morphological and molecular levels was evaluated and compared. Materials and Methods: The human endometrial tissues were cut into small fragments then they were randomly considered for transplantation into γ irradiated mice as model A; or they were isolated and cultured up to fourth passages. 2×106 cultured stromal cells were transplanted into γ irradiated mice subcutaneously as model B. twenty days later the ectopic tissues in both models were studied morphologically by Periodic acid-Schiff and hematoxylin and eosin staining. The expression of osteopontin (OPN) and matrix metalloproteinase 2 (MMP2) genes were also assessed using real time RT-PCR. 17-β estradiol levels of mice sera were compared before and after transplantation. Results: The endometrial like glands and stromal cells were formed in the implanted subcutaneous tissue of both endometriosis models. The gland sections per cubic millimeter, the expression of OPN and MMP2 genes and the level of 17-β estradiol were higher in model B than model A (p=0.03). Conclusion: Our observation demonstrated that endometrial mesenchymal stromal cells showed more efficiency to establish endometriosis model than human endometrial tissue fragments. PMID:28280797

  15. Meta-analysis of bipolar radiofrequency endometrial ablation versus thermal balloon endometrial ablation for the treatment of heavy menstrual bleeding.

    PubMed

    Zhai, Yan; Zhang, Zihan; Wang, Wei; Zheng, Tingping; Zhang, Huili

    2017-10-06

    Heavy menstrual bleeding is a common problem that can severely affect quality of life. To compare bipolar radiofrequency endometrial ablation and thermal balloon ablation for heavy menstrual bleeding in terms of efficacy and health-related quality of life (HRQoL). Online registries were systematically searched using relevant terms without language restriction from inception to November 24, 2016. Randomized control trials or cohort studies of women with heavy menstrual bleeding comparing the efficacy of two treatments were eligible. Data were extracted. Results were expressed as risk ratios (RRs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs). Six studies involving 901 patients were included. Amenorrhea rate at 12 months was significantly higher after bipolar radiofrequency endometrial ablation than after thermal balloon ablation (RR 2.73, 95% CI 2.00-3.73). However, no difference at 12 months was noted for dysmenorrhea (RR 1.04, 95% CI 0.68-1.58) or treatment failure (RR 0.78, 95% CI 0.38-1.60). The only significant difference for HRQoL outcomes was for change in SAQ pleasure score (12 months: WMD -3.51, 95% CI -5.42 to -1.60). Bipolar radiofrequency endometrial ablation and thermal balloon ablation reduce menstrual loss and improve quality of life. However, bipolar radiofrequency endometrial ablation is more effective in terms of amenorrhea rate and SAQ pleasure. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Correlation between body mass index and prevalence of hereditary nonpolyposis colorectal cancer in Korean patients with endometrial cancer.

    PubMed

    Yoo, Heon Jong; Joo, Jungnam; Seo, Sang-Soo; Kang, Sokbom; Yoo, Chong Woo; Park, Sang-Yoon; Lim, Myong Cheol

    2012-02-01

    The purpose of the study was to investigate the relationship between body mass index (BMI) and hereditary nonpolyposis colorectal cancer (HNPCC) in Korean women with endometrial cancer. Among 227 patients with endometrial cancer in the study population, 20 patients (8.8%) had HNPCC. The patients were divided into 2 groups based on the BMI: nonobese (BMI ≤25 kg/m) and obese (BMI >25 kg/m); then the nonobese group was subdivided into 2 groups: normal weight (BMI <23 kg/m) and overweight (BMI, 23-25 kg/m). The distributions of BMI categories were compared between patients with sporadic endometrial cancer and with HNPCC-related endometrial cancer. Among 207 patients with sporadic endometrial cancer, 119 (57.5%) were nonobese and 88 patients (42.5%) were obese. Of 20 patients with endometrial cancer related to HNPCC, 10 (50.0%) were nonobese and 10 (50.0%) were obese. In a subgroup analysis of only nonobese patients, 68 patients with sporadic endometrial cancer had normal weight and 51 were overweight. On the other hand, all 10 patients with HNPCC related to endometrial cancer had normal weight. There was no significant difference between the group with HNPCC-related endometrial cancer and the group with sporadic endometrial cancer according to BMI (P = 0.221). However, BMI proportions in HNPCC related to endometrial cancer were significantly different from those in sporadic endometrial cancer (P = 0.016). Among a subgroup of nonobese patients, the proportion of normal weight was significant higher in patients with HNPCC-related endometrial cancer compared to those in sporadic endometrial cancer (P = 0.006). Body mass index was not different between sporadic endometrial cancer and HNPCC-related endometrial cancer in Koreans. However, BMI proportions in the patients with HNPCC related to endometrial cancer was significantly different from those in sporadic endometrial cancer. Specifically, among nonobese patients, the proportion of normal weight was significantly high

  17. High Glucose-Mediated STAT3 Activation in Endometrial Cancer Is Inhibited by Metformin: Therapeutic Implications for Endometrial Cancer.

    PubMed

    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

    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. 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. 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. These results suggest that STAT3 expression in type 1 endometrial cancer is stimulated by a high glucose environment and inhibited by metformin.

  18. Endometrial spiral artery Doppler parameters in unexplained infertility patients: is endometrial perfusion an important factor in the etiopathogenesis?

    PubMed Central

    Uysal, Selda; Özbay, Elif Pelin Özün; Ekinci, Tekin; Aksüt, Hayri; Karasu, Şebnem; Işık, Ahmet Zeki; Soylu, Ferit

    2012-01-01

    Objective Uterine perfusion, particularly the endometrial blood flow, may have an important role in endometrial receptivity. In order to assess the contribution of sub endometrial blood flow in the etiopathogenesis of unexplained infertility mid luteal- peri-implantation period spiral artery transvaginal color Doppler parameters were measured and compared with fertile controls. Material and Methods Forty-two consecutive patients admitted to Izmir Katip Celebi University Ataturk Training and Research Hospital, Department of Obstetric and Gynecology with the diagnosis of unexplained infertility after standard diagnostic work up constituted the study group and they were compared with a fertile control group admitted to hospital with non specific gynecological complaints or for check-up in the same period. Mid luteal transvaginal color Doppler ultrasonography was applied to each patient by the same radiologist who was blind to the diagnosis of the particular patient and, RI (resistance index) and PI (pulsatility index) values were calculated. Results There were no significant differences between the two groups, in respect to age, body mass index, basal hormonal and mid luteal progesterone levels (p>0.05). For the fertile control group, mid luteal-peri-implantation phase endometrial spiral artery mean RI values were calculated as 0.48±0.08 SD and mean PI values as 0.65±0.18 SD. For the study group, mean RI values were calculated as 0.54±0.07 SD, PI values were calculated as 0.80±0.16 SD. The differences for RI (p=0.009) and PI (p=0.004) were statistically significant. Conclusion According to Doppler parameters, unexplained infertility patients have high impedance blood flow in spiral arteries which means that peri-implantation blood flow in these patient is lower than fertile controls. These findings suggest that endometrial perfusion may have an important contribution to etiopathogenesis of unexplained infertility. PMID:24592032

  19. Endometrial spiral artery Doppler parameters in unexplained infertility patients: is endometrial perfusion an important factor in the etiopathogenesis?

    PubMed

    Uysal, Selda; Ozbay, Elif Pelin Özün; Ekinci, Tekin; Aksüt, Hayri; Karasu, Sebnem; Işık, Ahmet Zeki; Soylu, Ferit

    2012-01-01

    Uterine perfusion, particularly the endometrial blood flow, may have an important role in endometrial receptivity. In order to assess the contribution of sub endometrial blood flow in the etiopathogenesis of unexplained infertility mid luteal- peri-implantation period spiral artery transvaginal color Doppler parameters were measured and compared with fertile controls. Forty-two consecutive patients admitted to Izmir Katip Celebi University Ataturk Training and Research Hospital, Department of Obstetric and Gynecology with the diagnosis of unexplained infertility after standard diagnostic work up constituted the study group and they were compared with a fertile control group admitted to hospital with non specific gynecological complaints or for check-up in the same period. Mid luteal transvaginal color Doppler ultrasonography was applied to each patient by the same radiologist who was blind to the diagnosis of the particular patient and, RI (resistance index) and PI (pulsatility index) values were calculated. There were no significant differences between the two groups, in respect to age, body mass index, basal hormonal and mid luteal progesterone levels (p>0.05). For the fertile control group, mid luteal-peri-implantation phase endometrial spiral artery mean RI values were calculated as 0.48±0.08 SD and mean PI values as 0.65±0.18 SD. For the study group, mean RI values were calculated as 0.54±0.07 SD, PI values were calculated as 0.80±0.16 SD. The differences for RI (p=0.009) and PI (p=0.004) were statistically significant. According to Doppler parameters, unexplained infertility patients have high impedance blood flow in spiral arteries which means that peri-implantation blood flow in these patient is lower than fertile controls. These findings suggest that endometrial perfusion may have an important contribution to etiopathogenesis of unexplained infertility.

  20. 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

  1. 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

  2. Transvaginal ultrasonography and hysteroscopy as predictors of endometrial polyps in postmenopause.

    PubMed

    de Godoy Borges, Pítia Cárita; Dias, Rogério; Bonassi Machado, Rogério; Borges, João Bosco Ramos; Spadoto Dias, Daniel

    2015-01-01

    The study compared ultrasound and ambulatorial hysteroscopy as diagnostic methods detecting endometrial polyps in postmenopause women. 281 women aged 41-82 years who underwent ambulatorial hysteroscopy were analyzed for presence of uterine bleeding and/or altered transvaginal ultrasound (endometrial thickness ≥5 mm). Ultrasonography detected endometrial polyps in 22.8% of patients and endometrial thickening in the other 59.8%. Hysteroscopy diagnosed endometrial polyps in 80.8%. Ultrasonography showed sensitivity of 88.7%, specificity of 25.4%, positive predictive value of 81.7%, negative predictive value of 37.5% and accuracy of 75.4% in diagnosing endometrial polyps. Hysteroscopy showed 96.4% sensitivity, 74.6% specificity, 93.4% positive predictive value, 84.6% negative predictive value and 91.8% accuracy. Hysteroscopy demonstrated more accuracy than ultrasonography, which is not sufficient for accurate diagnosis.

  3. Effects of metformin on endometrial cancer: Systematic review and meta-analysis.

    PubMed

    Meireles, Cinthia G; Pereira, Sidney A; Valadares, Luciana P; Rêgo, Daniela F; Simeoni, Luiz A; Guerra, Eliete N S; Lofrano-Porto, Adriana

    2017-10-01

    Endometrial cancer is one of the most common gynecological cancers, which is frequently preceded by atypical endometrial hyperplasia, a premalignant lesion. Metformin, an antidiabetic drug, has emerged as a new adjunctive strategy for different cancer types, including endometrial cancer. This systematic review and meta-analysis aimed to evaluate the effects of metformin in atypical endometrial hyperplasia and endometrial cancer patients. The search was conducted on January 2017 and the articles were collected in Cochrane, LILACS, PubMed, Scopus and Web of Science. A grey literature search was undertaken using Google SCHOLAR, ProQuest and Open Grey. Nineteen studies were included, which contained information about the following outcomes: reversal of atypical endometrial hyperplasia, cellular proliferation biomarkers expression and overall survival in metformin-users compared to non-users. Metformin was associated with reversion of atypical endometrial hyperplasia to a normal endometrial, and with decreased cell proliferation biomarkers staining, from 51.94% (CI=36.23% to 67.46%) to 34.47% (CI=18.55% to 52.43%). However, there is a high heterogeneity among studies. Metformin-users endometrial cancer patients had a higher overall survival compared to non-metformin users and non-diabetic patients (HR=0.82; CI: 0.70-0.95; p=0.09, I(2)=40%). Regardless the high heterogeneity of the analyzed studies, the present review suggests that adjunct metformin treatment may assist in the reversal of atypical endometrial hyperplasia to normal endometrial histology, in the reduction of cell proliferation biomarkers implicated in tumor progression, and in the improvement of overall survival in endometrial cancer. Further work on prospective controlled trials designed to address the effects of adjunct metformin on clinical outcomes is necessary for definite conclusions. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Role of spiral artery Doppler to screen type 2 endometrial cancer cases.

    PubMed

    Düzgüner, Soner; Ozkan, Mehmet Burak; Küçüközkan, Tuncay; Ozkaya, Enis; Kara, Fadıl; Balın, Ipek Nur; Korkmaz, Vakkas; Karslı, Mehmet Fatih; Gültekin, Burak

    2014-01-01

    The purpose of this study was to determine the value of endometrial blood flow assessment in predicting type 2 endometrial carcinoma. Sixty-five consecutive post-menopoausal women who had vaginal bleeding were enrolled in the study. All subjects were directed to transvaginal sonography to determine endometrial blood flow and underwent endometrial biopsy. Doppler findings were analysed to predict endometrial pathology. Subjects with unsatisfactory Doppler analyses were excluded from the study. Mean age of the study population was 50.1±6.9 years (42-73). Mean endometrial thickness was 10.1±2.9 mm (4-15 mm) and mean cancer antigen 125 (CA125) level was 20.1±17.4 U/mL (3-92). Histopathological evaluation revealed 14 cases of type 2 endometrial cancer and 18 cases of endometrial hyperplasia without atypia, while the other 33 cases had normal endometrial tissue. CA125 (Area under curve (AUC)=0.853, p=0.000), spiral artery resistance index (AUC=0.905, p=0.000), and spiral artery peak systolic velocity (AUC=0.822, p=0.000) were significant predictors for the type 2 endometrial cancer cases. Endometrial thickness did not significantly predict pathologic cases (p>0.05). Hyperplasia cases were not predicted by any of these diagnostic modalities (p>0.05). In patients with postmenopausal bleeding, spiral artery Doppler ultrasound, could play a role in refining the diagnosis of type 2 endometrial carcinoma; however, its predictive value should be evaluated with further studies.

  5. Prediction of Treatment Outcomes After Global Endometrial Ablation

    PubMed Central

    El-Nashar, Sherif A.; Hopkins, Matthew R.; Creedon, Douglas J.; St. Sauver, Jennifer L.; Weaver, Amy L.; McGree, Michaela E.; Cliby, William A.; Famuyide, Abimbola O.

    2010-01-01

    Objective To report rates of amenorrhea and treatment failure after global endometrial ablation and to estimate the association between patient factors and these outcomes by developing and validating prediction models. Methods From January 1998 through December 2005, 816 women underwent global endometrial ablation with either a thermal balloon ablation or radiofrequency ablation device; 455 were included in a population-derived cohort (for model development), and 361 were included in a referral-derived cohort (for model validation). Amenorrhea was defined as cessation of bleeding from immediately after ablation through at least 12 months after the procedure. Treatment failure was defined as hysterectomy or re-ablation for patients with bleeding or pain. Logistic and Cox proportional hazard regression models were used in model development and validation of potential predictors of outcomes. Results The amenorrhea rate was 23% (95% confidence interval [CI], 19%–28%) and the 5-year cumulative failure rate was 16% (95% CI, 10%–20%). Predictors of amenorrhea were age 45 years or older (adjusted odds ratio [aOR], 2.6; 95% CI, 1.6–4.3); uterine length less than 9 cm (aOR, 1.8; 95% CI, 1.1–3.1); endometrial thickness less than 4 mm (aOR, 2.7; 95% CI, 1.2–6.3); and use of radiofrequency ablation instead of thermal balloon ablation (aOR, 2.8; 95% CI, 1.7–4.9). Predictors of treatment failure included age younger than 45 years (adjusted hazard ratio [aHR], 2.6; 95% CI, 1.3–5.1); parity of 5 or greater (aHR, 6.0; 95% CI, 2.5–14.8); prior tubal ligation (aHR, 2.2; 95% CI, 1.2–4.0); and history of dysmenorrhea (aHR, 3.7; 95% CI, 1.6–8.5). After global endometrial ablation, 23 women (5.1%; 95% CI, 3.2%–7.5%) had pelvic pain, 3 (0.7%; 95% CI, 0.1%–1.9%) were pregnant, and none (95% CI, 0%–0.8%) had endometrial cancer. Conclusion Population-derived rates and predictors of treatment outcomes after global endometrial ablation may help physicians offer optimal

  6. Mig-6 suppresses endometrial cancer associated with Pten deficiency and ERK activation.

    PubMed

    Kim, Tae Hoon; Yoo, Jung-Yoon; Kim, Hong Im; Gilbert, Jenifer; Ku, Bon Jeong; Li, Jane; Mills, Gordon B; Broaddus, Russell R; Lydon, John P; Lim, Jeong Mook; Yoon, Ho-Geun; Jeong, Jae-Wook

    2014-12-15

    PTEN mutations are the most common genetic alterations in endometrial cancer. Loss of PTEN and subsequent AKT activation stimulate estrogen receptor α-dependent pathways that play an important role in endometrial tumorigenesis. The major pathologic phenomenon of endometrial cancer is the loss of ovarian steroid hormone control over uterine epithelial cell proliferation and apoptosis. However, the precise mechanism of PTEN/AKT signaling in endometrial cancer remains poorly understood. The progesterone signaling mediator MIG-6 suppresses estrogen signaling and it has been implicated previously as a tumor suppressor in endometrial cancer. In this study, we show that MIG-6 also acts as a tumor suppressor in endometrial cancers associated with PTEN deficiency. Transgenic mice, where Mig-6 was overexpressed in progesterone receptor-expressing cells, exhibited a relative reduction in uterine tumorigenesis caused by Pten deficiency. ERK1/2 was phosphorylated in uterine tumors and administration of an ERK1/2 inhibitor suppressed cancer progression in PR(cre/+)Pten(f/f) mice. In clinical specimens of endometrial cancer, MIG-6 expression correlated inversely with ERK1/2 phosphorylation during progression. Taken together, our findings suggest that Mig-6 regulates ERK1/2 phosphorylation and that it is crucial for progression of PTEN-mutant endometrial cancers, providing a mechanistic rationale for the evaluation of ERK1/2 inhibitors as a therapeutic treatment in human endometrial cancer. ©2014 American Association for Cancer Research.

  7. Mig-6 suppresses endometrial cancer associated with Pten deficiency and ERK activation

    PubMed Central

    Kim, Tae Hoon; Yoo, Jung-Yoon; Kim, Hong Im; Gilbert, Jenifer; Ku, Bon Jeong; Li, Jane; Mills, Gordon B.; Broaddus, Russell R.; Lydon, John P.; Lim, Jeong Mook; Yoon, Ho-Geun; Jeong, Jae-Wook

    2014-01-01

    PTEN mutations are the most common genetic alterations in endometrial cancer. Loss of PTEN and subsequent AKT activation stimulate ERα-dependent pathways that play an important role in endometrial tumorigenesis. The major pathologic phenomenon of endometrial cancer is the loss of ovarian steroid hormone control over uterine epithelial cell proliferation and apoptosis. However, the precise mechanism of PTEN/AKT signaling in endometrial cancer remains poorly understood. The progesterone signaling mediator MIG-6 suppresses estrogen signaling and it has been implicated previously as a tumor suppressor in endometrial cancer. In this study, we show that MIG-6 also acts as a tumor suppressor in endometrial cancers associated with PTEN deficiency. Transgenic mice where Mig-6 was overexpressed in PR-expressing cells exhibited a relative reduction in uterine tumorigenesis caused by Pten deficiency. ERK1/2 was phosphorylated in uterine tumors and administration of an ERK1/2 inhibitor suppressed cancer progression in PRcre/+Ptenf/f mice. In clinical specimens of endometrial cancer, MIG-6 expression correlated inversely with ERK1/2 phosphorylation during progression. Taken together, our findings suggest that Mig-6 regulates ERK1/2 phosphorylation and that it is crucial for progression of PTEN-mutant endometrial cancers, providing a mechanistic rationale for the evaluation of ERK1/2 inhibitors as a therapeutic treatment in human endometrial cancer. PMID:25377472

  8. Endometrial receptivity profile in patients with premature progesterone elevation on the day of HCG administration.

    PubMed

    Haouzi, Delphine; Bissonnette, Laurence; Gala, Anna; Assou, Said; Entezami, Frida; Perrochia, Hélène; Dechaud, Hervé; Hugues, Jean-Noel; Hamamah, Samir

    2014-01-01

    The impact of a premature elevation of serum progesterone level, the day of hCG administration in patients under controlled ovarian stimulation during IVF procedure, on human endometrial receptivity is still debated. In the present study, we investigated the endometrial gene expression profile shifts during the prereceptive and receptive secretory stage in patients with normal and elevated serum progesterone level on the day of hCG administration in fifteen patients under stimulated cycles. Then, specific biomarkers of endometrial receptivity in these two groups of patients were tested. Endometrial biopsies were performed on oocyte retrieval day and on day 3 of embryo transfer, respectively, for each patient. Samples were analysed using DNA microarrays and qRT-PCR. The endometrial gene expression shift from the prereceptive to the receptive stage was altered in patients with high serum progesterone level (>1.5 ng/mL) on hCG day, suggesting accelerated endometrial maturation during the periovulation period. This was confirmed by the functional annotation of the differentially expressed genes as it showed downregulation of cell cycle-related genes. Conversely, the profile of endometrial receptivity was comparable in both groups. Premature progesterone rise alters the endometrial gene expression shift between the prereceptive and the receptive stage but does not affect endometrial receptivity.

  9. Human Papillomavirus in Endometrial Adenocarcinomas: Infectious Agent or a Mere “Passenger”?

    PubMed Central

    Giatromanolaki, A.; Sivridis, E.; Papazoglou, D.; Koukourakis, M. I.; Maltezos, E.

    2007-01-01

    Aims. To investigate the possible association of human papillomavirus (HPV) with endometrial hyperplasias and neoplasia. Does HPV play any role in the initiation or prognosis of endometrial adenocarcinomas? Methods. Twenty-five endometrial adenocarcinomas of the endometrioid cell type, with and without squamous differentiation, and twenty-four endometrial hyperplasias of various forms (simple, complex, and atypical) were analyzed for the presence of type 16 and 18 HPV by the polymerase chain reaction (PCR). The results were related to histopathological features of the tumour, and the patients' age, and prognosis. Results. Six of 25 endometrial adenocarcinomas were HPV 16-positive (24%), and 5 of 25 (20%) were HPV 18-positive. Simple endometrial hyperplasias was associated somewhat more commonly with HPV 16 and 18 (2/8 and 1/8 cases, resp.) than hyperplasias progressing to endometrial adenocarcinomas, namely, atypical endometrial hyperplasia (1/8 and 0/8 cases, resp.). None of the positive cases in the series, whether hyperplastic or neoplastic, demonstrated cytological evidence of HPV infection. There was no relation between HPV-positive cases and squamous differentiation, depth of myometrial invasion, lymphatic involvement, lymphocytic response, patients' age, or prognosis. Conclusion. It appears that the presence of HPV in the endometrium, as detected by PCR, does not play any role in the initiation or prognosis of endometrial adenocarcinoma. PMID:18274613

  10. Dasatinib in Treating Patients With Recurrent or Persistent Ovarian, Fallopian Tube, Endometrial or Peritoneal Cancer

    ClinicalTrials.gov

    2017-04-13

    Endometrial Clear Cell Adenocarcinoma; Estrogen Receptor Negative; Ovarian Clear Cell Cystadenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma

  11. Oncogenic histone methyltransferase EZH2: A novel prognostic marker with therapeutic potential in endometrial cancer

    PubMed Central

    Oki, Shinya; Sone, Kenbun; Oda, Katsutoshi; Hamamoto, Ryuji; Ikemura, Masako; Maeda, Daichi; Takeuchi, Makoto; Tanikawa, Michihiro; Mori-Uchino, Mayuyo; Nagasaka, Kazunori; Miyasaka, Aki; Kashiyama, Tomoko; Ikeda, Yuji; Arimoto, Takahide; Kuramoto, Hiroyuki; Wada-Hiraike, Osamu; Kawana, Kei; Fukayama, Masashi; Osuga, Yutaka; Fujii, Tomoyuki

    2017-01-01

    The histone methyltransferase EZH2, a key epigenetic modifier, is known to be associated with human tumorigenesis. However, the physiological importance of EZH2 and its clinical relevance in endometrial cancer remain unclear. Hence, in the present study, we investigated the expression and function of EZH2 in endometrial cancer. In a quantitative real-time PCR analysis of 11 endometrial cancer cell lines and 52 clinical endometrial cancer specimens, EZH2 was significantly overexpressed in cancer cells and tissues compared to that in corresponding normal control cells and tissues. Kaplan-Meier survival analysis using data of the TCGA RNA-seq database and tissue microarrays (TMAs) indicated that EZH2 overexpression is associated with endometrial cancer prognosis. In addition, knockdown of EZH2 using specific siRNAs resulted in growth suppression and apoptosis induction of endometrial cancer cells, accompanied by attenuation of H3K27 trimethylation. Consistent with these results, treatment with GSK126, a specific EZH2 inhibitor, suppressed endometrial cancer cell growth and decreased the number of cancer cell colonies. Furthermore, GSK126 showed additive effects with doxorubicin or cisplatin, which are conventional drugs for treatment of endometrial cancer. Further studies should explore the therapeutic potential of inhibiting EZH2 in patients with endometrial cancer. PMID:28418882

  12. Implantation in the baboon: endometrial responses.

    PubMed

    Fazleabas, A T; Kim, J J; Srinivasan, S; Donnelly, K M; Brudney, A; Jaffe, R C

    1999-01-01

    Blastocyst implantation in the baboon usually occurs between 8 and 10 days post ovulation. Changes that occur within this window of receptivity and immediately following implantation can be divided into three distinct phases. The first phase, regulated by estrogen and progesterone, is characterized primarily by changes in both the luminal and glandular epithelial cells in preparation for blastocyst apposition and attachment. The second phase is the further modulation of these steroid induced changes in both epithelial and stromal cells by embryonic signals. The final phase is associated with trophoblast invasion and the remodeling of the endometrial stromal compartment. During the initial phase, the actions of estrogen and progesterone are dependent on the presence of specific receptors. Estrogen up-regulates both its own receptor (ER) and the progesterone receptor (PR), while progesterone down-regulates this expression pattern. However, the pattern of progesterone-induced down-regulation of ER and PR is confined to the epithelial cells and demonstrates a gradient effect from the functionalis to the basalis. What is most intriguing is that the loss of epithelial PR is closely correlated with the establishment of uterine receptivity. Coincident with the changes in ER and PR expression, epithelial cells undergo alterations in their cytoskeletal architecture and secretory profile. These changes can be counteracted by PR antagonist treatment during the luteal phase. Although estrogen and progesterone play a critical role in establishing the initial phase of uterine receptivity, it is becoming increasingly evident that the embryo induces functional receptivity in ruminants and rodents. In our studies in the primate, we demonstrate that chorionic gonadotrophin when infused in a manner that mimics blastocyst transit, has physiological effects on the three major cell types in the uterine endometrium. The luminal epithelium undergoes endoreplication and distinct epithelial

  13. Endometrial exosomes/microvesicles in the uterine microenvironment: a new paradigm for embryo-endometrial cross talk at implantation.

    PubMed

    Ng, York Hunt; Rome, Sophie; Jalabert, Audrey; Forterre, Alexis; Singh, Harmeet; Hincks, Cassandra L; Salamonsen, Lois A

    2013-01-01

    Exosomes are nanoparticles (∼100 nm diameter) released from cells, which can transfer small RNAs and mRNA via the extracellular environment to cells at distant sites. We hypothesised that exosomes or the slightly larger microvesicles (100-300 nm) are released from the endometrial epithelium into the uterine cavity, and that these contain specific micro (mi)RNA that could be transferred to either the trophectodermal cells of the blastocyst or to endometrial epithelial cells, to promote implantation. The aim of this study was to specifically identify and characterise exosomes/microvesicles (mv) released from endometrial epithelial cells and to determine whether exosomes/mv are present in uterine fluid. Immunostaining demonstrated that the tetraspanins, CD9 and CD63 used as cell surface markers of exosomes are present on the apical surfaces of endometrial epithelial cells in tissue sections taken across the menstrual cycle: CD63 showed cyclical regulation. Exosome/mv pellets were prepared from culture medium of endometrial epithelial cell (ECC1 cells) and from uterine fluid and its associated mucus by sequential ultracentifugation. Exosomes/mv were positively identified in all preparations by FACS and immunofluorescence staining following exosome binding to beads. Size particle analysis confirmed the predominance of particles of 50-150 nm in each of these fluids. MiRNA analysis of the ECC1 cells and their exosomes/mv demonstrated sorting of miRNA into exosomes/mv: 13 of the 227 miRNA were specific to exosomes/mv, while a further 5 were not present in these. The most abundant miRNA in exosomes/mv were hsa-miR-200c, hsa-miR-17 and hsa-miR-106a. Bioinformatic analysis showed that the exosome/mv-specific miRNAs have potential targets in biological pathways highly relevant for embryo implantation. Thus exosomes/mv containing specific miRNA are present in the microenvironment in which embryo implantation occurs and may contribute to the endometrial-embryo cross talk

  14. Isolation and characterization of the pig endometrial arylsulphatase A.

    PubMed Central

    Rahi, H; Srivastava, P N

    1983-01-01

    The pig endometrial arylsulphatase A was purified 3322-fold to a specific activity of 150 mumol/min per mg. The purification involved (NH4)2SO4 fractionation, chromatography on concanavalin A-Sepharose and DEAE-Sepharose, gel filtrations on Sephadex G-200 at pH 7.4 and 5, and a new preparative gel-electrophoresis technique. The homogeneous enzyme is a glycoprotein containing 20% carbohydrate. The purified enzyme has Mr about 120 000 and it contains subunits of Mr 63 000. The pig endometrial arylsulphatase A shows many properties in common with those of arylsulphatases A purified from other sources. The similarities include their low isoelectric points, the anomalous time-activity relationships, multi-pH optima, inhibition by SO3(2-), SO4(2-), phosphate ions, metal ions and nucleoside phosphates, pH- and ionic-strength-dependent polymerization and amino acid composition. PMID:6136269

  15. Endometrial Tuberculosis Simulating an Ovarian Cancer: a case report.

    PubMed

    Di Giovanni, Silvia Eleonora; Cunha, Teresa Margarida; Duarte, Ana Luisa; Alves, Ines

    2016-06-01

    Female genital tuberculosis remains a major health problem in developing countries and is an important cause of infertility. As symptoms, laboratory data and physical findings are non-specific, its diagnosis can be difficult. We describe a case of a 39-year-old woman suffering from peri-umbilical pain and increased abdominal size for one year, anorexia, asthenia, weight loss, occasionally dysuria and dyspareunia, and four months amenorrhea. Laboratory data revealed cancer antigen 125 (CA-125) level of 132.3 U/mL, erythrocyte sedimentation rate of 42 mm/h, and gamma-globulins of 2.66 g/dL. Computed tomography scan showed loculated ascites. It was initially suspected a carcinomatous origin, but ascites evaluation was negative for malignant cells. Magnetic resonance imaging from another hospital showed endometrial heterogeneity. Therefore, an endometrial biopsy was performed demonstrating an inflammatory infiltrate with giant cells of type Langhans and bacteriological culture identified Mycobacterium tuberculosis.

  16. Elucidating endometrial function in the post-genomic era.

    PubMed

    Giudice, Linda C

    2003-01-01

    The post-genomic era has now arrived, and science and biology are on the threshold of a transition from understanding functions of single molecules and pathways in cells, tissues and whole organisms to understanding integrative systems. The endometrium is a dynamic tissue that responds to multiple stimuli, depending on physiological and environmental conditions, including steroid hormones, an implanting conceptus, withdrawal of steroid hormones, contraceptive steroids, selective steroid hormone receptor modulators, infection, transient cell populations, and metaplastic and neoplastic agents. High throughput technologies with regard to DNA, RNA and proteins are well positioned to enable a thorough understanding of the dynamic changes and integrative systems involved in endometrial maturation, desquamation, receptivity to implantation, infertility, pregnancy maintenance and failure, inflammation and infection, and malignant transformation. This monograph reviews some of the salient features of the new technologies and summarizes current information on endometrial biology derived from these approaches.

  17. Current Issues in the Diagnosis and Treatment of Endometrial Carcinoma

    PubMed Central

    Stubert, J.; Gerber, B.

    2016-01-01

    Endometrial carcinoma is the most common carcinoma of the female genital tract. Its most important clinical sign is postmenopausal bleeding. An endometrial biopsy is essential for diagnosis. Treatment decisions are governed by tumour risk assessment and patient comorbidity, which is often present. Pelvic and paraaortic lymph node dissection is unnecessary in low risk cases (definition: pT1 a, G1/2) and adjuvant radiotherapy and systemic treatments are usually avoidable. Treatment of high-risk patients (G3 and/or pT1b) and palliative cases is difficult and not well standardised. New molecular-based subtype classification may help treatment decision making in future. PMID:26941450

  18. Cell cycle regulation of human endometrial stromal cells during decidualization.

    PubMed

    Logan, Philip C; Steiner, Michael; Ponnampalam, Anna P; Mitchell, Murray D

    2012-08-01

    Differentiation of endometrial stromal cells into decidual cells is crucial for optimal endometrial receptivity. Data from our previous microarray study implied that expression of many cell cycle regulators are changed during decidualization and inhibition of DNA methylation in vitro. In this study, we hypothesized that both the classic progestin treatment and DNA methylation inhibition would inhibit stromal cell proliferation and cell cycle transition. The human endometrial stromal cell line (HESC) was treated from 2 days to 18 days with the DNA methylation inhibitor, 5-aza-2'-deoxycytidine (AZA), a mixture of estradiol/progestin/cyclic adenosine monophosphate ([cAMP]; medroxy-progesterone acetate [MPA mix]) or both. Cell growth was measured by cell counting, cell cycle transition and apoptosis were analyzed by flow cytometry, expression of cell cycle regulators were analyzed by quantitative polymerase chain reaction (qPCR) and Western blotting, and change in DNA methylation profiles were detected by methylation-specific PCR. Both AZA and MPA mix inhibited the proliferation of HESC for at least 7 days. Treatment with MPA mix resulted in an early G0/G1 inhibition followed by G2/M phase inhibition at 18 days. In contrast, AZA treatment inhibited cell cycle progression at the G2/M phase throughout. The protein levels of p21(Cip1)and 14-3-3σ were increased with both AZA and MPA mix treatments without any change in the DNA methylation profiles of the genes. Our data imply that the decidualization of HESC is associated with cell cycle arrest at G0/G1 phase initially and G2/M phase at later stages. Our results also suggest that p53 pathway members play a role in the cell cycle regulation of endometrial stromal cells.

  19. Endometrial cancer following radiation therapy for cervical cancer

    SciTech Connect

    Gallion, H.H.; van Nagell, J.R. Jr.; Donaldson, E.S.; Powell, D.E.

    1987-05-01

    The clinical and histologic features of eight cases of carcinoma of the endometrium which developed following radiation therapy for squamous cell carcinoma of the cervix are described. No patient had a well-differentiated tumor and significant myometrial invasion was present in all cases. Three of the eight tumors were papillary serous adenocarcinoma. Five of the eight patients developed recurrent tumor and died of their disease. The risk of endometrial cancer in patients previously radiated for cervical cancer is evaluated.

  20. Menstrual physiology: implications for endometrial pathology and beyond

    PubMed Central

    Maybin, Jacqueline A.; Critchley, Hilary O.D.

    2015-01-01

    BACKGROUND Each month the endometrium becomes inflamed, and the luminal portion is shed during menstruation. The subsequent repair is remarkable, allowing implantation to occur if fertilization takes place. Aberrations in menstrual physiology can lead to common gynaecological conditions, such as heavy or prolonged bleeding. Increased knowledge of the processes involved in menstrual physiology may also have translational benefits at other tissue sites. METHODS Pubmed and Cochrane databases were searched for all original and review articles published in English until April 2015. Search terms included ‘endometrium’, ‘menstruation’, ‘endometrial repair’, ‘endometrial regeneration’ ‘angiogenesis’, ‘inflammation’ and ‘heavy menstrual bleeding’ or ‘menorrhagia’. RESULTS Menstruation occurs naturally in very few species. Human menstruation is thought to occur as a consequence of preimplantation decidualization, conferring embryo selectivity and the ability to adapt to optimize function. We highlight how current and future study of endometrial inflammation, vascular changes and repair/regeneration will allow us to identify new therapeutic targets for common gynaecological disorders. In addition, we describe how increased knowledge of this endometrial physiology will have many translational applications at other tissue sites. We highlight the clinical applications of what we know, the key questions that remain and the scientific and medical possibilities for the future. CONCLUSIONS The study of menstruation, in both normal and abnormal scenarios, is essential for the production of novel, acceptable medical treatments for common gynaecological complaints. Furthermore, collaboration and communication with specialists in other fields could significantly advance the therapeutic potential of this dynamic tissue. PMID:26253932

  1. Are endometrial carcinoma cells disseminated at hysteroscopy functionally viable?

    PubMed

    Arikan, G; Reich, O; Weiss, U; Hahn, T; Reinisch, S; Tamussino, K; Pickel, H; Desoye, G

    2001-11-01

    The aim of this study was to evaluate the rate of transtubal dissemination of endometrial carcinoma cells by hysteroscopy and the functional viability of disseminated tumor cells by assessing cell adhesion in an in vitro model. We studied 24 uteri obtained at TAH+BSO in patients with endometrial carcinoma. Further inclusion criteria were negative peritoneal cytology, no involvement of the uterine serosa or extrauterine disease, and endometrial surface involvement >1 cm in diameter. In vitro fluid hysteroscopy was performed with a 5-mm single-flow rigid hysteroscope. A maximum of 150 ml saline was infused at a maximum pressure of 100 mm Hg for a maximum of 3 min. Fluid running off through the tubes was collected. The cell suspension was enriched by a density gradient centrifugation. The isolated cells had a mean viability of 90% as judged by trypan blue exclusion. Viable cells (5 x 10(4) per 2-cm(2) polyvinyl chloride well plate) were cultured with equal parts of Dulbecco's modified Eagle's minimal essential medium and Ham's F-12 for 24 h. The endpoint of the analysis was the adherence of tumor cells to the polyvinyl chloride well plate, which was taken as a proxy for functional cell viability. Cytological evaluation was performed separately by two cytologists blinded to the source and date of the smears. Transtubal fluid dissemination was seen in 20 of 24 (83%) uteri. Tumor cells were found in 17 specimens (71%). In 10 (42%) specimens the disseminated tumor cells were functionally viable. Our model suggests that hysteroscopy can cause dissemination of malignant cells into the abdominal cavity from uteri containing endometrial carcinoma and that these cells can be functionally viable and adhere to a matrix. Copyright 2001 Academic Press.

  2. A comparison of endometrial cancer outcomes in Ontario.

    PubMed

    Kwon, Janice S; Bryson, Peter; Liu, Grace; Peterson, Kathryn; Stewart, Moira; Davis, Roger B; Cook, E Francis

    2004-09-01

    To compare endometrial cancer treatment strategies and outcomes across the province of Ontario, Canada. A retrospective cohort study was conducted of 195 women diagnosed with endometrial cancer in Ontario between 1996 and 1998, as a sample of the population. The women's charts were randomly selected by the medical records departments at 5 tertiary care centres in Ontario. The outcomes measured included 5-year overall survival (OS) and disease-free survival (DFS), use of adjuvant radiotherapy, treatment complications, and prognostic factors for survival. The 2 main treatment strategies were (1) total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH BSO) and (2) surgical staging (defined as TAH BSO and pelvic lymph node dissection with or without cytology, peritoneal biopsies, and omentectomy). Surgical staging rates across the province ranged from 0% to 88%. Stratified survival analysis revealed a significant difference in OS among centres (log rank P =.039). Crude survival analysis revealed no difference in 5-year OS or DFS between the 2 treatment strategies. The Cox proportional hazards model identified advanced stage of tumour as being the most predictive factor of DFS, and the woman's age at diagnosis and tumour grade as predictive of OS. There was a significant difference in 5-year OS among the 5 tertiary care centres. There was no significant difference between surgical staging and TAH BSO with respect to 5-year DFS or OS. As there were significant differences in the treatment of endometrial carcinoma and OS across the province, a population-based study of endometrial cancer treatment strategies and outcomes is required.

  3. Post treatment surveillance of type II endometrial cancer patients.

    PubMed

    Zakhour, Mae; Li, Andrew J; Walsh, Christine S; Cass, Ilana; Karlan, Beth Y; Rimel, B J

    2013-12-01

    There are few studies analyzing surveillance for Type II endometrial cancer recurrence. Our objective was to determine the types of post treatment surveillance tests performed in our institution and the efficacy of these tests in detecting recurrence in type II endometrial cancer patients. One hundred and thirty six cases of type II endometrial cancers at Cedars-Sinai Medical Center from January of 2000 to August of 2011 were identified and 106 patients met inclusion criteria. Medical charts were reviewed for surveillance methods and number of follow up visits. For patients who underwent a recurrence of disease, the surveillance method utilized for detection was documented. Forty-seven of the 106 (44%) patients developed recurrence with a mean progression free interval of 11 months. All patients had a history and physical at each surveillance visit, 78% had Pap testing, 57% had CA-125 levels drawn, 59% had CT (computed tomography) scans done, 6% had PET (positron emission tomography) scans done for surveillance. In our cohort, recurrence was detected by symptoms in 16, by CA-125 in 11, by physical exam in 7, by CT scan in 12, and by PET scan in one patient. No patients had recurrence detected by vaginal cytology. Although performed in the majority of patients, Pap testing did not detect any recurrences within this cohort. History and physical exam detected the most recurrences. These findings suggest that educating patients about relevant symptoms and performing thorough follow-up exams may be the most important aspects of detecting type II endometrial cancer recurrence. © 2013.

  4. The role of robotic surgery in endometrial cancer.

    PubMed

    O'Malley, David M; Smith, Blair; Fowler, Jeffrey M

    2015-12-01

    Robotic surgery for endometrial cancer has less blood loss, shorter hospital stays, and less postoperative complications compared to laparotomies. Robotic technologic advantages over laparoscopic technique are most pronounced in obese patients. The shorter learning curve may explain the greater utilization of the robotic technique. Robotic surgery will continue as a mainstay in the treatment of uterine cancers as we become more efficient and cost conscious while maintaining the high quality outcomes that have been reported.

  5. Metabolic syndrome and endometrial cancer: a meta-analysis.

    PubMed

    Esposito, Katherine; Chiodini, Paolo; Capuano, Annalisa; Bellastella, Giuseppe; Maiorino, Maria Ida; Giugliano, Dario

    2014-02-01

    We performed a systematic review and meta-analysis on the association of metabolic syndrome with endometrial cancer. A systematic literature search of electronic databases (Medline, ISI Web of Knowledge and Scopus) was conducted and complemented by cross-referencing to identify studies published before 31 January 2013. Core items of identified studies were independently extracted by two reviewers, and results were summarized by random effects meta-analysis. We identified six studies, which reported on 3,132 cancer cases. Metabolic syndrome was associated with an increased risk of endometrial cancer (RR: 1.89, 95 % CI 1.34-2.67, P < 0.001), with significant heterogeneity among studies (I (2) = 92 %, P < 0.001), but no indication for publication bias in the Egger's test (P = 0.240). A sensitivity analysis omitting two studies produced no heterogeneity (I (2) = 0 %) and attenuated the association (RR: 1.39, 1.31-1.48, P < 0.001). The risk estimates for any single factor of the syndrome were 2.21 (P < 0.001) for higher values of body mass index and/or waist, 1.81 (P = 0.044) for hyperglycemia, 1.81 (P = 0.024) for higher blood pressure values, and 1.17 (P < 0.001) for high triglyceride levels; there was no significant association with low HDL-cholesterol. Metabolic syndrome is associated with an increased risk of endometrial cancer; among the components of the syndrome, obesity/high waist is that more strongly associated with endometrial cancer.

  6. Stage IB endometrial cancer. Does lymphadenectomy replace adjuvant radiotherapy?

    PubMed

    Bottke, Dirk; Wiegel, Thomas; Kreienberg, Rolf; Kurzeder, Christian; Sauer, Georg

    2007-11-01

    The role of surgical lymph node dissection and adjuvant radiation therapy (RT) in early stage endometrial cancer is no longer clearly defined. The increased appreciation of lymphadenectomy and the absence of survival advantage from adjuvant RT rise controversies how patients should adequately be treated in stage IB endometrial cancer. The aim of this review is to rule out the validity of either treatment option and determine which preference provides the best therapeutic benefit. Reports of relevant studies obtained from a search of PubMed and studies referenced in those reports were reviewed. Based on the available data in the literature, for stage IB grade 1 or 2, the risk of pelvic relapse is considered too low to justify pelvic RT. However, intravaginal RT (IVRT) should be recommended for those >or= 60 years old or with lymphovascular invasion (LVI). For patients with stage IB grade 3 (and IC all grades), the treatment recommendation is mainly based on whether surgical lymph node staging was performed. These patients have--without surgical lymph node staging--a high risk of pelvic recurrence and should therefore primarily undergo relaparotomy for lymphadenectomy or pelvic RT as second choice. If these patients had a surgical lymph node staging, then IVRT alone is a reasonable alternative to pelvic RT. Overall survival may not be the only ideal endpoint for stage IB endometrial cancer since causes of death are mostly other than endometrial cancer. Conventional pelvic RT may be overtreatment in some patients, in particular in those patients with a large number of negative lymph nodes after lymphadenectomy. However, negative surgical staging should not be understood as adjuvant RT can be omitted in all patients.

  7. A clinically applicable molecular-based classification for endometrial cancers.

    PubMed

    Talhouk, A; McConechy, M K; Leung, S; Li-Chang, H H; Kwon, J S; Melnyk, N; Yang, W; Senz, J; Boyd, N; Karnezis, A N; Huntsman, D G; Gilks, C B; McAlpine, J N

    2015-07-14

    Classification of endometrial carcinomas (ECs) by morphologic features is inconsistent, and yields limited prognostic and predictive information. A new system for classification based on the molecular categories identified in The Cancer Genome Atlas is proposed. Genomic data from the Cancer Genome Atlas (TCGA) support classification of endometrial carcinomas into four prognostically significant subgroups; we used the TCGA data set to develop surrogate assays that could replicate the TCGA classification, but without the need for the labor-intensive and cost-prohibitive genomic methodology. Combinations of the most relevant assays were carried forward and tested on a new independent cohort of 152 endometrial carcinoma cases, and molecular vs clinical risk group stratification was compared. Replication of TCGA survival curves was achieved with statistical significance using multiple different molecular classification models (16 total tested). Internal validation supported carrying forward a classifier based on the following components: mismatch repair protein immunohistochemistry, POLE mutational analysis and p53 immunohistochemistry as a surrogate for 'copy-number' status. The proposed molecular classifier was associated with clinical outcomes, as was stage, grade, lymph-vascular space invasion, nodal involvement and adjuvant treatment. In multivariable analysis both molecular classification and clinical risk groups were associated with outcomes, but differed greatly in composition of cases within each category, with half of POLE and mismatch repair loss subgroups residing within the clinically defined 'high-risk' group. Combining the molecular classifier with clinicopathologic features or risk groups provided the highest C-index for discrimination of outcome survival curves. Molecular classification of ECs can be achieved using clinically applicable methods on formalin-fixed paraffin-embedded samples, and provides independent prognostic information beyond

  8. [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.

  9. Independent prognostic value of peritoneal immunocytodiagnosis in endometrial carcinoma.

    PubMed

    Benevolo, M; Mariani, L; Vocaturo, G; Vasselli, S; Natali, P G; Mottolese, M

    2000-02-01

    Among the clinical parameters that play a pivotal role in predicting the outcome of patients with endometrial carcinoma, intraperitoneal microscopic dissemination represents an important cause of recurrences. To date, peritoneal cytology has been incorporated into the current surgical staging system (International Federation of Gynecology and Obstetrics 88), although its predictive value remains a controversial issue. In this study the authors investigated the possibility of applying immunocytochemistry (ICC) to the diagnosis of peritoneal washing (PW) aimed at improving conventional cytology and verifying the prognostic value of peritoneal malignant cells. The authors analyzed 182 PWs sampled from endometrial cancer patients. The ICC analysis was performed using two monoclonal antibodies (MAbs)--AR-3 and B72.3--that in combination recognize more than 95% of endometrial carcinomas. The presence of peritoneal-free cancer cells was identified morphologically in 27 of 182 lavages (14.8%) and ICC in 50 of 182 (27.5%), with a significant improvement (p <0.0001). Five-year survival analysis, comparing results of ICC and cytodiagnosis, demonstrated a significant decrease of disease-free survival in patients with peritoneal microscopic disease. Furthermore, multivariate analysis showed that ICC diagnosis of PWs is an independent prognostic factor. Data indicate that the use of selected MAbs allows one to identify cytologically false-negative cases, providing results that are highly predictive of a worse clinical outcome.

  10. Bladder and bowel symptoms in cervical and endometrial cancer survivors.

    PubMed

    Donovan, Kristine A; Boyington, Alice R; Judson, Patricia L; Wyman, Jean F

    2014-06-01

    Previous studies likely underestimate the prevalence of bowel and bladder symptoms in gynecologic cancer survivors. We sought to estimate the prevalence of these symptoms in cervical and endometrial cancer survivors who had completed treatment 1 year previously compared with non-cancer controls, and to examine factors associated with more severe symptoms in survivors. As part of a larger quality of life study, survivors who were 1-year posttreatment for cervical or endometrial cancer (n = 104) completed measures of bladder and bowel symptoms. An age-matched and race/ethnicity-matched sample of women with no history of cancer was recruited for comparison purposes. Survivors reported a higher prevalence of bladder symptoms, specifically storage and incontinence symptoms, than non-cancer controls. Prevalence rates for bowel symptoms in survivors were higher than those reported in previous studies. Greater symptom severity was associated with younger age, lower annual incomes, and less education. Other correlates included higher body mass index and history of smoking. As hypothesized, more severe symptoms were associated with radical hysterectomy and pelvic radiation. Bladder and bowel symptoms are more prevalent in cervical and endometrial cancer survivors than non-cancer controls. Future research should replicate these findings in a larger, prospective study. Copyright © 2014 John Wiley & Sons, Ltd.

  11. The complementary deoxyribonucleic acid sequence of guinea pig endometrial prorelaxin.

    PubMed

    Lee, Y A; Bryant-Greenwood, G D; Mandel, M; Greenwood, F C

    1992-03-01

    The nucleotide sequence of the relaxin gene transcript in the endometrium of the late pregnant guinea pig has been determined. The strategy used was a combination of polymerase chain reaction (PCR) with primers designed from the mRNA sequence of porcine preprorelaxin, rapid amplification of cDNA ends-PCR, and blunt end cloning in M13 mp18. With heterologous primers, a 226-basepair (bp) segment of the guinea pig relaxin gene sequence was obtained and was used to design a guinea pig-specific primer for use with the rapid amplification of cDNA ends-PCR method. The latter allowed completion of the sequence of 336 bp, with a 96-bp overlap. The sequence obtained shows greater homology at both the nucleotide and amino acid levels with porcine and human relaxins H1 and H2 than with rat relaxin, supporting the thesis that the guinea pig is not a rodent. The transcription of the guinea pig endometrial relaxin gene during pregnancy was confirmed by Northern analysis of guinea pig endometrial tissues with a species-specific cDNA probe. The endometrial relaxin gene is transcribed during pregnancy, but not in lactation, consistent with the observed immunostaining for relaxin.

  12. Unusual inflammation in gynecologic pathology associated with defective endometrial receptivity.

    PubMed

    Kitaya, Kotaro; Yasuo, Tadahiro; Tada, Yoshihiro; Hayashi, Terumi; Iwaki, Yuri; Karita, Masako; Funabiki, Miyako; Taguchi, Sagiri; Spillers, Dustin; Nakamura, Yoshitaka; Yamada, Hisao

    2014-09-01

    Human cycling endometrium displays a series of periodic transitions unique to this mucosal tissue, which includes rapid proliferation, secretory transformation, physiological angiogenesis, interstitial edema, and menstrual shedding. Among these properties of the endometrium are the inflammatory changes that occur dynamically across the menstrual cycle. Immunocompetent cell composition and inflammatory gene expression pattern in the human endometrium drastically fluctuate from the proliferative phase to the secretory phase, particularly at the time of ovulation. These local immune responses are fine-tuned by the direct or indirect action of two representative ovarian steroids, estradiol and progesterone, and are essential for successful blastocyst implantation. Meanwhile, studies have been accumulating the evidence that such physiological endometrial inflammatory status is altered in the presence of certain gynecologic pathologies. Given that blastocysts are semi-allografts for maternal tissue, even subtle alterations in endometrial immunity potentially have a negative impact on implantation process. In this article, we aimed to review and discuss the physiological and pathological mucosal inflammatory conditions that can affect endometrial receptivity.

  13. Alteration of endometrial receptivity in rats with ovarian hyperstimulation syndrome.

    PubMed

    Xu, C-K; Tang, S-B

    2014-02-01

    It is unclear if the higher pregnancy rate in patients who experience ovarian hyperstimulation syndrome (OHSS) indicates that OHSS is favourable for embryo implantation, or if patients should be maintained in a hyperstimulation state in order to increase the success rate of embryo transplantation. We developed an animal model to determine the endometrial receptivity in rats with OHSS. Endometrial mRNA levels of ER, PR, HOXA10 and LIF were determined by semi-quantitative PCR and ER, PR, HOXA10, LIF and integrin α(v) β(3) protein levels were determined by Western blotting. Development of pinopodes in the hyperstimulation group was slightly delayed, while in the regular stimulation group, development was significantly inhibited. mRNA transcription in the regular stimulation group was lower, while transcription in the hyperstimulation group was not different from controls. Protein expressions were lowest in the regular stimulation. We conclude that OHSS is associated with favourable endometrial receptivity, similar to that seen in a normal cycle, and receptivity that is increased relative to that seen with a routine stimulation protocol.

  14. Pancreatic endometrial cyst mimics mucinous cystic neoplasm of the pancreas

    PubMed Central

    Mederos, Michael A; Villafañe, Nicole; Dhingra, Sadhna; Farinas, Carlos; McElhany, Amy; Fisher, William E; Van Buren II, George

    2017-01-01

    Pancreatic cysts include a variety of benign, premalignant, and malignant lesions. Endometrial cysts in the pancreas are exceedingly rare lesions that are difficult to diagnose pre-operatively. This report describes the findings in a 43-year-old patient with a recent episode of acute pancreatitis who presented with a large cyst in the tail of the pancreas. Imaging demonstrated a loculated pancreatic cyst, and cyst fluid aspiration revealed an elevated amylase and carcinoembryonic antigen. The patient experienced an interval worsening of abdominal pain, fatigue, diarrhea, and a 15-pound weight loss 3 mo after the initial episode of pancreatitis. With concern for a possible pre-malignant lesion, the patient underwent a laparoscopic distal pancreatectomy with splenectomy, which revealed a 16 cm × 12 cm × 4 cm lesion. Final histopathology was consistent with an intra-pancreatic endometrial cyst. Here we discuss the overlapping imaging and laboratory features of pancreatic endometrial cysts and mucinous cystic neoplasms of the pancreas. PMID:28246486

  15. The Inflammation Response to DEHP through PPARγ in Endometrial Cells

    PubMed Central

    Huang, Qiansheng; Zhang, Huanteng; Chen, Ya-Jie; Chi, Yu-Lang; Dong, Sijun

    2016-01-01

    Epidemiological studies have shown the possible link between phthalates and endometrium-related gynecological diseases, however the molecular mechanism(s) behind this is/are still unclear. In the study, both primary cultured endometrial cells and an endometrial adenocarcinoma cell line (Ishikawa) were recruited to investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) at human-relevant concentrations. The results showed that DEHP did not affect the viability of either type of cell, which showed different responses to inflammation. Primary cultured cells showed stronger inflammatory reactions than the Ishikawa cell line. The expression of inflammatory factors was induced both at the mRNA and protein levels, however the inflammation did not induce the progress of epithelial-mesenchymal transition (EMT) as the protein levels of EMT markers were not affected after exposure to either cell type. Further study showed that the mRNA levels of peroxisome proliferator-activated receptor gamma (PPARγ) wereup-regulated after exposure. In all, our study showed that human-relevant concentrations of DEHP could elicit the inflammatory response in primary cultured endometrial cells rather than in Ishikawa cell line. PPARγ may act as the mediating receptor in the inflammation reaction. PMID:26985901

  16. Pseudo-placentational endometrial cysts in a bitch.

    PubMed

    Bartel, C; Schönkypl, S; Walter, I

    2010-02-01

    Cystic alterations of the canine endometrium compromise reproduction and fertility of the bitch and may lead to life-threatening diseases, such as pyometra. Even without clinical evidence, reduction of the uterine lumen by cysts implicates disturbances during migration, nidation and development of the embryo. Several studies point to the high variability of morphology of uterine endometrial cysts but they lack detailed analyses of alterations. In the present study, immunohistochemistry was used to investigate the expression of steroid hormone receptors (oestrogen, progesterone), proliferation activity, inflammation and infection in the cystic affected tissue regions in contrast to the normal endometrium. Oestrogen receptor expression showed a high density of receptors throughout the surface epithelial cells, crypt epithelial cells, glandular epithelial cells and stromal cells of the normal endometrium as well as the cystic affected regions. Proliferation in the cysts was verified in the middle and basal cells of the crypts. Neither in the endometrium nor in the cysts inflammatory processes or evidence of infection could be detected. Furthermore, lectin histochemistry and electron microscopic methods showed that lectin binding patterns and cell morphology of internal epithelial lining and surface epithelium of the cysts can be used to characterize and distinguish different types of cystic alterations. Analogies between epithelial cells of the glandular chambers of the canine placenta and the cystic cellular morphology, steroid hormone receptor distribution as well as lectin binding patterns of the endometrial cysts, as observed in this study, suggest to introduce the term 'pseudo-placentational endometrial cysts'.

  17. Supporting patients following pelvic radiotherapy for endometrial cancer.

    PubMed

    Elliot, Emma

    Endometrial cancer is the commonest gynaecological cancer in the UK. Affected women often live with long-term complex and debilitating side-effects of radiotherapy treatment, such as bowel toxicity, fatigue and psychosexual problems. Women also experience negative feelings around self-image and sexuality, which contribute to a decline in their quality of life. A review of the literature and national policy showed that women had unmet needs after completing radiotherapy treatment for endometrial cancers, and that cancer nurse specialists are in a prime position to deliver a holistic package of personalized care. Staff at a nurse-led gynaecology oncology clinic performed an audit that found the clinic was not meeting the longer-term needs of most women after radiotherapy for endometrial cancers, and that women were attending multiple appointments to access different services. The clinical nurse specialist reviewed local and national policy, carried out situational analysis and engaged with service users to identify where change was needed and to examine whether a new model of service provision, where patients could consult different professionals at one appointment, would help the move forward in life after treatment.

  18. Common genetic variation within IGFI, IGFII, IGFBP-1, and IGFBP-3 and endometrial cancer risk

    PubMed Central

    McGrath, Monica; Lee, I-Min; Buring, Julie; De Vivo, Immaculata

    2011-01-01

    Objective The insulin-like growth factor (IGF) pathway plays a critical role in the growth and development of the uterus and is believed to function as a mediator of steroid hormone actions in the endometrium. The local expression of genes encoding IGFs and IGF-binding proteins (IGFBPs) are important in determining IGF bioactivity in the uterus. Genetic variation in key genes within the IGF pathway may influence the rate of cellular proliferation and differentiation in the uterus and ultimately affect the risk of endometrial cancer. Our hypothesis is that variant alleles in key genes involved in the IGF pathway will influence the development of endometrial cancer. Methods We conducted a case-control study nested within the Nurses’ Health Study (NHS) and the Women's Health Study (WHS) to investigate the association between forty-four polymorphisms within IGFI, IGFII, IGFBP-1, and IGFBP-3 with endometrial cancer risk using 692 invasive endometrial cancer cases and 1723 matched controls. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the risk of endometrial cancer. Results We observed an inverse association with IGFII rs3741211 and endometrial cancer risk (OR = 0.79 (95% CI: 0.63, 0.99)) and IGFII rs1004446 and endometrial cancer risk (OR = 0.80 (95% CI: 0.68, 0.94)). We also observed an inverse association with IGFBP-3 rs2453839 and endometrial cancer risk (OR= 0.81 (95%CI: 0.67, 0.98). However, we did not observe any statistically significant associations with the polymorphisms in IGFI and IGFBP1 and endometrial cancer risk. Conclusions Genetic variation with IGFII and IGFBP-3 may influence endometrial cancer risk in Caucasians. Polymorphisms in IGFI and IGFBP-1 were not associated with endometrial cancer risk, but further research is needed. PMID:21078522

  19. Detection of chromosomal anomalies in endometrial atypical hyperplasia and carcinoma by using fluorescence in situ hybridization.

    PubMed

    Qian, Junqi; Weber, Deena; Cochran, Richard; Hossain, Deloar; Bostwick, David G

    2010-04-25

    Endometrial cancer is the most common pelvic gynecological malignancy. The diagnosis of well-differentiated endometrial adenocarcinoma, atypical hyperplasia, and hyperplasia is often challenging. The authors sought to investigate the utility of chromosomal anomalies for the detection of endometrial hyperplasia and carcinoma using multitarget fluorescence in situ hybridization (FISH). Samples were collected by endometrial Tao brush and processed by liquid-based cytological preparation protocol from consecutive cases to include 50 benign, 50 hyperplasia without atypia, 47 atypical hyperplasia, and 53 endometrial cancers. Each was hybridized using fluorescence-labeled DNA probes to chromosomes 1, 8, and 10. The FISH signals were enumerated in 100 cells per case, and the chromosomal anomalies were correlated with pathologic findings, including histologic diagnoses on matched endometrial tissue samples. Numeric chromosomal anomalies were found in 0% (0 of 50) of benign, 20% (10 of 50) of hyperplasia, 74% (35 of 47) of atypical hyperplasia, and 87% (46 of 53) of carcinoma specimens. The mean percentage of cells with chromosomal changes was 55% in cancer specimens, which was significantly higher than that in hyperplasia without atypia (13%, P < .0001) and atypical hyperplasia (32%, P = .003). The most frequent chromosomal anomaly was gain of chromosome 1. FISH anomalies had an overall sensitivity of 81% and specificity of 90% for the detection of atypical hyperplasia and/or endometrial carcinoma. There was no association with grade of endometrial carcinoma. Multitarget FISH appears to be useful for the differential diagnosis of hyperplasia, atypical hyperplasia, and endometrial adenocarcinoma, with a high level of sensitivity and specificity. It is also a potential tool for the early detection of neoplastic cells in endometrial cytology specimens. Endometrial hyperplasia with FISH-detected chromosomal anomalies may represent a clinically significant subset of cases that

  20. Statin use and risk of endometrial cancer: a nationwide registry-based case-control study.

    PubMed

    Sperling, Cecilie D; Verdoodt, Freija; Friis, Søren; Dehlendorff, Christian; Kjaer, Susanne K

    2017-02-01

    Laboratory and epidemiological evidence have suggested that statin use may protect against the development of certain cancers, including endometrial cancer. In a nationwide registry-based case-control study, we examined the association between statin use and risk of endometrial cancer. Cases were female residents of Denmark with a primary diagnosis of endometrial cancer during 2000-2009. For each case, we selected 15 female population controls matched on date of birth (±one month) using risk-set sampling. Ever use of statin was defined as two or more prescriptions on separate dates. Conditional logistic regressions were used to estimate age-matched (by design) and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CI) for endometrial cancer associated with statin use. The multivariable-adjusted models included parity, hormone replacement therapy (HRT), obesity, diabetes, chronic obstructive pulmonary disease and education. We evaluated whether the association between statin use and endometrial cancer varied with duration and intensity of statin use, type of endometrial cancer or patient characteristics. The study population comprised 5382 endometrial cancer cases and 72 127 population controls. We observed no association between ever use of statins and endometrial cancer risk (OR 1.03, 95% CI 0.94-1.14). In addition, endometrial cancer risk did not vary substantially with duration or intensity of statin use. Stratification by type of endometrial cancer also yielded neutral ORs. In our nationwide case-control study, we found no association between statin use and risk of endometrial cancer. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  1. Androgens Upregulate Endometrial Epithelial Progesterone Receptor Expression: Potential Implications for Endometriosis.

    PubMed

    Babayev, Samir N; Park, Chan Woo; Keller, Patrick W; Carr, Bruce R; Word, Ruth A; Bukulmez, Orhan

    2017-10-01

    Androgenic compounds have been implicated in induction of endometrial atrophy yet the mechanisms of androgen effects on human endometrium have not been well studied. We hypothesized that androgens may promote their endometrial effects via modulation of progesterone receptor (PR) expression. Proliferative phase endometrial samples were collected at the time of hysterectomy. We evaluated the effect of the potent androgen 5α-dihydrotestosterone (DHT) on endometrial PR expression by treating human endometrial explants, endometrial stromal cells, and Ishikawa cells with DHT. Ishikawa cells were also treated with DHT ± the androgen receptor (AR) blocker flutamide. The PR-B, total PR messenger RNA (mRNA), and PR protein expression were assessed. Expression of cyclin D1 and D2 was checked as markers of cell proliferation. As expected, estradiol induced PR expression in isolated stromal cells, endometrial epithelial cells, and tissue explants. The DHT treatment also resulted in increased PR expression in endometrial explants and Ishikawa cells but not in stromal cells. Further, protein levels of both nuclear PR isoforms (PR-A and PR-B) were induced with the DHT treatment. Although flutamide treatment alone did not affect PR expression, flutamide diminished androgen-induced upregulation of PR in both endometrial explants and Ishikawa cells. Although estradiol induced both cyclin D1 and cyclin D2 mRNA, DHT did not induce these markers of cell proliferation. Androgens may mediate endometrial effects through upregulation of PR gene and protein expression. Endometrial PR upregulation by androgens is mediated, at least in part, through AR.

  2. The value of diagnostic hysteroscopy with biopsy in the preoperative of endometrial ablation.

    PubMed

    Yatabe, Salete; Pereira, Ana Maria Gomes; Takeda, Gilberto Kendi; Depes, Daniela de Baptista; Lopes, Reginaldo Guedes Coelho

    2011-12-01

    To assess the value of diagnostic hysteroscopy with biopsy in the preoperative preparation for endometrial ablation. It was a prospective non-randomized study conducted at the division of Gynecologic Endoscopy of Hospital do Servidor Público Estadual "Francisco Morato de Oliveira" from March 2007 to May 2009. A total of 45 patients with abnormal uterine bleeding, and referred to endometrial ablation were included. All women underwent a diagnostic hysteroscopy, and were treated with a GnRH analogous - goserelin - 10.8 mg before surgery. The endometrial ablation was performed with a surgical resectoscope. Patients were submitted to one directed endometrial biopsy, one guided endometrial biopsy with Novak curette, and to endometrial ablation, which was considered as reference for pathological examination with samples from the biopsies. Data were analyze using the SPSS-v16 software, and considered significance at p = 0.05. The mean age of women was 44.20 years (33-56), parity of 2.67 (0-9), uterus size of 139.99 calculated in cc (42-278), and the mean duration of symptoms was 3.68 years (0.5-15). The guided endometrial biopsy showed sensitivity of 80% for endometrium without atypia, and the directed endometrial biopsy had sensitivity of 60%. For proliferative endometrium the directed endometrial biopsy showed sensitivity of 76 and 100% for secretory endometrium, which was higher than the guided endometrial biopsy with 53 and 50%, respectively. The directed biopsy before endometrial ablation had lower sensitivity than guided biopsy for endometrium without atypia, however it was higher for proliferative and secretory endometrium.

  3. Positive predictive value of endometrial polyps in Pipelle aspiration sampling: a histopathological study of 195 cases.

    PubMed

    Seto, Mimi T Y; Ip, Philip P C; Ngu, Siew-Fei; Cheung, Annie N Y; Pun, Ting-Chung

    2016-08-01

    To estimate the positive predictive value of Pipelle endometrial sampling in detecting the presence of an underlying endometrial polyp. The secondary objective is to examine the histologic features that can predict the presence of endometrial polyps. This is a retrospective case review study. 195 women who had undergone diagnostic hysteroscopy and/or polypectomy were identified in a University teaching hospital. All patients had a prior polyp diagnosis in the Pipelle endometrial sample. The histology of these samples were compared and analyzed with subsequent DH findings and final hysteroscopic biopsies. Slides were reviewed by 2 gynaecological pathologists. 162 women were premenopausal (mean age 46.1, SD=4.6) and 33 were postmenopausal (mean age 57.2, SD=8.1). The commonest indication for a Pipelle endometrial sampling was abnormal uterine bleeding. Presence of polyp was confirmed by DH in 56.3% (111/195) cases. Of these, 81.1% (90/111) were confirmed histologically. The positive predictive value of detection of polyps in Pipelle endometrial samples for premenopausal and postmenopausal women was 53.7% and 72.7%, respectively (p=.05). The most reliable histologic features that can predict the presence of an underlying polyp was fibrous stroma (p=.01) and focal glandular clustering (p=.03). The prevalence of endometrial hyperplasia and carcinoma in women who was confirmed to have polyp was 11.7% (13/111). The positive predictive value of Pipelle endometrial samples in detecting endometrial polyps was 56.3%. It was higher in the postmenopausal women (72.7%) compared to premenopausal women (53.7%). The prevalence of endometrial hyperplasia and carcinoma in women who was confirmed to have polyp was consistent with the rate reported in the literature. Using ultrasonography as an adjunct maybe helpful in diagnosing endometrial polyps. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. 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

  5. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of Liver and Endometrial cancer Risk following Tamoxifen.

    PubMed

    Bergman, L; Beelen, M L; Gallee, M P; Hollema, H; Benraadt, J; van Leeuwen, F E

    2000-09-09

    Tamoxifen increases the risk of endometrial cancer. However, few studies have produced reliable risk estimates by duration, dose, and recency of use, or addressed the prognosis of endometrial cancers in tamoxifen-treated women. We did a nationwide case-control study on the risk and prognosis of endometrial cancer after tamoxifen use for breast cancer. Information on tamoxifen use and other risk factors for endometrial cancer was obtained from 309 women with endometrial cancer after breast cancer (cases), and 860 matched controls with breast cancer but without endometrial cancer. For 276 cases, we obtained tissue blocks of endometrial cancer to review the diagnosis, and used immunohistochemistry to examine hormone-receptor status and overexpression of p53. Tamoxifen had been used by 108 (36.1%) of 299 cases and 245 (28.5%) controls (relative risk 1.5 [95% CI 1.1-2.0]). Risk of endometrial cancer increased with longer duration of tamoxifen use (p < 0.001), with relative risks of 2.0 (1.2-3.2) for 2-5 years and 6.9 (2.4-19.4) for at least 5 years compared with non-users. Endometrial cancers of stage III and IV occurred more frequently in long-term tamoxifen users (> or = 2 years) than in non-users (17.4% vs 5.4%, p=0.006). Long-term users were more likely than non-users to have had malignant mixed mesodermal tumours or sarcomas of the endometrium (15.4% vs 2.9%, p < or = 0.02), p53-positive tumours (31.4% vs 18.2%, p=0.05), and negative oestrogen-receptor concentrations (60.8% vs 26.2%, p < or = 0.001). 3-year endometrial-cancer-specific survival was significantly worse for long-term tamoxifen users than for non-users (76% for > or = 5 years, 85% for 2-5 years vs 94% for non-users, p=0.02). Long-term tamoxifen users have a worse prognosis of endometrial cancers, which seems to be due to less favourable histology and higher stage. However, the benefit of tamoxifen on breast-cancer survival far outweighs the increased mortality from endometrial cancer. Nevertheless, we

  6. Immunohistochemical detection of P-glycoprotein in endometrial adenocarcinoma.

    PubMed Central

    Axiotis, C. A.; Monteagudo, C.; Merino, M. J.; LaPorte, N.; Neumann, R. D.

    1991-01-01

    P-glycoprotein (Pgp) has emerged as the central mediator in classic multidrug resistance in model systems in vitro. High levels of Pgp also have been detected in many normal human tissues and tumors; and its role in clinical drug resistance is currently under investigation. Recently significant levels of Pgp were localized to gravid and secretory endometrium; and it was demonstrated that the combination of estrogen and progesterone is sufficient to induce high levels of both Pgp mRNA and Pgp in uterine secretory epithelium. These findings suggest that increased Pgp expression also may be present in hormone-responsive malignancies such as endometrial adenocarcinoma. To determine whether Pgp is expressed in endometrial adenocarcinoma, 36 endometrial adenocarcinomas (grade I [n = 17]; grade II [n = 6]; grade III [n = 13]) were investigated retrospectively by the avidin-biotin-complex immunohistochemical procedure using three murine monoclonal antibodies (MAb) MAb C219, MAb C494, and MAb JSB-1, which recognize spatially distinct cytoplasmic epitopes of Pgp. Seventy-two percent of the tumors showed positive immunostaining with at least one MAb; 67% showed immunostaining with MAb C219, 50% with MAb C494, and 62% with MAb JSB-1. Forty-six percent of tumors were immunoreactive to two and 29% to all three antibodies. Membranous and Golgi/paranuclear type staining patterns were observed. Overall the intensity of immunostaining varied from one sample to another for a given tumor type, and considerable heterogeneity of expression was commonly seen within a given tumor. Strong to moderate immunoreactivity was seen in diffusely infiltrating, adenosquamous, and serous papillary carcinomas. In general, immunoreactivity to MAb C494 was weaker than MAb C219 or MAb JSB-1. Adenomatous and non-neoplastic endometrium adjacent to the tumors displayed strong membranous immunostaining with MAb JSB-1. Endometrial capillaries showed weak-to-moderate immunostaining to all three antibodies. It

  7. The genetic landscape of endometrial clear cell carcinomas.

    PubMed

    DeLair, Deborah F; Burke, Kathleen A; Selenica, Pier; Lim, Raymond S; Scott, Sasinya N; Middha, Sumit; Mohanty, Abhinita S; Cheng, Donavan T; Berger, Michael F; Soslow, Robert A; Weigelt, Britta

    2017-10-01

    Clear cell carcinoma of the endometrium is a rare type of endometrial cancer that is generally associated with an aggressive clinical behaviour. Here, we sought to define the repertoire of somatic genetic alterations in endometrial clear cell carcinomas (ECCs), and whether ECCs could be classified into the molecular subtypes described for endometrial endometrioid and serous carcinomas. We performed a rigorous histopathological review, immunohistochemical analysis and massively parallel sequencing targeting 300 cancer-related genes of 32 pure ECCs. Eleven (34%), seven (22%) and six (19%) ECCs showed abnormal expression patterns for p53, ARID1A, and at least one DNA mismatch repair (MMR) protein, respectively. Targeted sequencing data were obtained from 30 of the 32 ECCs included in this study, and these revealed that two ECCs (7%) were ultramutated and harboured mutations affecting the exonuclease domain of POLE. In POLE wild-type ECCs, TP53 (46%), PIK3CA (36%), PPP2R1A (36%), FBXW7 (25%), ARID1A (21%), PIK3R1 (18%) and SPOP (18%) were the genes most commonly affected by mutations; 18% and 11% harboured CCNE1 and ERBB2 amplifications, respectively, and 11% showed DAXX homozygous deletions. ECCs less frequently harboured mutations affecting CTNNB1 and PTEN but more frequently harboured PPP2R1A and TP53 mutations than non-POLE endometrioid carcinomas from The Cancer Genome Atlas (TCGA). Compared to endometrial serous carcinomas (TCGA), ECCs less frequently harboured TP53 mutations. When a surrogate model for the molecular-based TCGA classification was used, all molecular subtypes previously identified in endometrial endometrioid and serous carcinomas were present in the ECCs studied, including POLE, MMR-deficient, copy-number high (serous-like)/p53 abnormal, and copy-number low (endometrioid)/p53 wild-type, which were significantly associated with disease-free survival in univariate analysis. These findings demonstrate that ECCs constitute a histologically and

  8. Obesity risk awareness in women with endometrial cancer.

    PubMed

    Connor, Elizabeth V; Raker, Christina A; Clark, Melissa A; Stuckey, Ashley R

    2017-04-01

    To assess whether women with endometrial cancer could accurately classify their weight and identify the association between obesity and risk of endometrial, breast, and colon cancers. This was an IRB-approved (Project No. 14-0075), survey-based cross-sectional study of women ages 18-80 years with a diagnosis of endometrial cancer. Patients were at least 6 months from hysterectomy and 3 months from chemotherapy or radiation. Statistical analysis was completed using Fisher's exact test, T test, ANOVA, Wilcoxon rank-sum test, or Kruskal-Wallis test. P values were two-tailed with P < 0.05 considered statistically significant. 140 women met inclusion criteria, and 133 questionnaires (95.0%) were completed. Mean age was 63.2 years (range 35-80), and mean BMI was 33.4 kg/m(2) (range 17.6-72.2). Patients were primarily Caucasian (88.7%) and reported education beyond high school (67.8%). Among women with BMI 30.0-34.99 kg/m(2), 12.9% perceived themselves as obese, compared to 32.0% of women with BMI 35.0-39.99 kg/m(2), and 72.7% of women with BMI >40.0 kg/m(2). Ability to correctly classify weight correlated significantly with education level (P = 0.02). Less than half of women identified obesity as a risk factor for breast (49.6%), colon (48.1%), and endometrial cancer (44.4%). 77% of all patients had discussed weight with their primary care doctor, and 38% had discussed weight with their oncologist (P < 0.001). The majority of obese women with endometrial cancer surveyed were unable to accurately classify their weight. Given the inconsistency between patient weight and perception of cancer risk, this represents an opportunity for gynecologic oncologists to educate their patients about weight control.

  9. Frequency of Adequate Endometrial Biopsy in Evaluation of Postmenopausal Women With Benign Endometrial Cells on Pap Test.

    PubMed

    Hastings, Jeffrey W; Alston, Meredith J; Mazzoni, Sara E; Stickrath, Elaine

    2017-10-01

    The aim of the study was to determine the frequency that endometrial biopsies (EMBs) performed on postmenopausal (PMP) women with benign endometrial cells (BECs) on Pap test are adequate for assessing malignancy or hyperplasia. This is a case series including all PMP women older than 55 years at a single academic institution between January 2008 and September 2015 with a Pap test result including BEC. Patients were identified via an internal cytology database. Patient data, the ability to obtain an EMB, and the result of the EMB were collected. An adequate EMB was defined as the presence of glands and stroma sufficient to assess for endometrial hyperplasia and/or malignancy. Descriptive statistics were performed, and then univariable and logistic regression analyses were used to evaluate associations of patient factors and adequacy of EMB. One hundred sixteen women met inclusion criteria. One hundred seven had an EMB scheduled (92%) and of those 91 EMBs were obtained (85%). Of the obtained biopsies, 63 were inadequate to rule out the diagnosis of hyperplasia and/or malignancy (69%). Of these, 19 patients underwent pelvic ultrasound (30%), 12 followed up with repeat Pap test (19%), and 4 underwent dilation and curettage (6%). Of the adequate biopsies, 5 had a diagnosis of hyperplasia (18%) and 5 with malignancy (18%). In PMP women with BEC on Pap test, adequate EMB was only obtained in 31% of patients. Most patients without an adequate biopsy had no further workup of their abnormal Pap test.

  10. [Clinical application of adult comorbidity evaluation-27 in endometrial cancer].

    PubMed

    Tian, W Y; Wang, Y M; Yan, Y; Gao, J P; Sun, D D; Jiang, S; Sheng, Y; Teng, F; Xue, F X

    2016-11-25

    Objective: To investigate the significant role of the clinical application of adult comorbidity evaluation-27 (ACE-27) in endometrial cancer (EC). Methods: A total of 847 EC patients were included during Jan. 1985 to Dec. 2015 from Tianjin Medical University General Hospital. The clinical data of the patients were collected and analyzed retrospectively. All of the patients were received operation with no chemotherapy and radiotherapy before operation. The average age was 57.6 years old (range from 25 to 85 years old). The average follow-up period was 59.0 months (range from 2 to 312 months). The comorbidity of the patients was evaluated by ACE-27. EC patients survival was analyzed by Kaplan-Meier survival curve. The relationship between the prognosis of EC and ACE-27, age, body mass index (BMI) , pathological characteristic were showed by Cox modeling. Results: (1) The patient number of score 0, 1, 2 and 3 of ACE-27 in EC patients were respectively 311 (36.7%), 263 (31.1%), 132 (15.6%) and 141 (16.6%) cases. (2) Kaplan-Meier survival curve analysis showed that overall survival time of EC patients was gradually decreased as increased score of ACE-27 (χ(2)=19.003, P=0.000) . In the patients of BMI<25 kg/m(2) and BMI 25-<30 kg/m(2), International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ, endometrial adenocarcinoma type and the overall survival time of those EC patients were gradually decreased as increased score of ACE-27 (P<0.05) . However, there was no statistically significant difference in overall survival time for patients with BMI ≥30 kg/m(2), FIGO stage with Ⅱ-Ⅳand non-endometrial adenocarcinoma type (P>0.05). Per unvariate logistic modeling showed that the risk of death in score 3 of ACE-27 was increased compared with score 0 of ACE-27 (OR=2.53, P=0.000) . The overall survival time in EC patients with aged 50-59, 60-69 and ≥70 years old, BMI 25-<30 kg/m(2) and ≥ 30 kg/m(2), G3, FIGO stage Ⅱ-Ⅳ and non-endometrial adenocarcinoma

  11. 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

  12. 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…

  13. 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.

  14. Controlled ovarian hyperstimulation for in vitro fertilization alters endometrial receptivity in humans: protocol effects.

    PubMed

    Haouzi, Delphine; Assou, Said; Dechanet, Clothilde; Anahory, Tal; Dechaud, Hervé; De Vos, John; Hamamah, Samir

    2010-04-01

    The impact of gonadotropin-releasing hormone (GnRH) agonist long compared with GnRH antagonist protocols, under in vitro fertilization conditions on endometrial receptivity, is still debated. Therefore, we compared the effect of both GnRH antagonist and agonist long protocols on the endometrial receptivity by analyzing, to our knowledge for the first time, the global gene expression profile shift during the prereceptive and receptive stages of stimulated cycles under the two GnRH analogue protocols compared with natural cycles in the same patients. For the same normal-responder patients, endometrial biopsies were collected on the day of oocyte retrieval and on the day of embryo transfer after human chorionic gonadotropin administration of a stimulated cycle with either GnRH agonist long or GnRH antagonist protocols and compared with the prereceptive and receptive stages of a natural cycle. Samples were analyzed using DNA microarrays. Gene expression profiles and biological pathways involved during the prereceptive stage to the receptive endometrial transition of stimulated and natural cycles were analyzed and compared for each patient. Both protocols affect endometrial receptivity in comparison with their natural cycle in the same patients. Major differences in endometrial chemokines and growth factors under stimulated cycles in comparison with natural cycles were observed. Such an effect has been associated with gene expression alterations of endometrial receptivity. However, the endometrial receptivity under the GnRH antagonist protocol was more similar to the natural cycle receptivity than that under the GnRH agonist protocol.

  15. 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…

  16. Expression of Ki-67 as proliferation biomarker in imprint smears of endometrial carcinoma.

    PubMed

    Konstantinos, Kosmas; Marios, Stamoulas; Anna, Marouga; Nikolaos, Kavantzas; Efstratios, Patsouris; Paulina, Athanassiadou

    2013-03-01

    The aims of this study were to determine the expression of Ki-67 in type I and type II endometrial adenocarcinomas as well as normal endometrium in imprint smears and to correlate the results with clinicopathologic parameters of primary untreated endometrial cancer patients. During a 29-month period, 255 patients were evaluated with entometrial imprint cytology. Endometrial samples freshly resected from women who underwent total abdominal hysterectomy were studied. One hundred twenty-six patients had endometrial carcinoma and 129 cases were diagnosed as normal endometrium. The expression of Ki-67 was assessed by immunocytochemistry. Positive staining was correlated with increased stage, grade and lymph node metastases. High expression was more frequent in type II than type I endometrial adenocarcinoma and high-grade endometrial carcinoma had higher proportions of Ki-67 positive immunostaining compared with low-grade carcinoma. Proliferative endometrium showed high Ki-67 expression level, even higher than those of grade 1 and type I. On the other hand, secretory endometrium Ki-67 positive cells were markedly diminished and even disappeared. Completely negative staining was found to be related to atrophic endometrium. Immunocytochemical findings from Ki-67 stain, in addition to cytomorphologic features, appeared to be useful for the diagnosis of endometrial carcinoma in endometrial cytology with imprint smears. High Ki-67 expression correlates with morphologic features of aggressiveness and the expression pattern of Ki-67 correspond to the expected cyclic/atrophic pattern in normal endometrium.

  17. Endometrial tubal metaplasia in a young puerperal woman after breast cancer

    PubMed Central

    Di Benedetto, Luisa; Giovanale, Valentina; Caserta, Donatella

    2015-01-01

    Introduction: Tamoxifen is the usual endocrine (anti-estrogen) therapy for hormone receptor-positive breast cancer in pre and post-menopausal women. Previous studies have suggested an increased prevalence of endometrial diseases after treatment with tamoxifen. Case presentation: The authors report a case of 38-year-old woman with diagnosis of endometrial polyp and tubal metaplasia, during puerperium and after micropapillary ductal breast cancer surgery, 5 years of tamoxifen treatment, spontaneous pregnancy without complications and full-term vaginal delivery. Conclusion: Tamoxifen is a safe and reliable treatment of breast cancer, but data suggest an association with endometrial polyps, hyperplasia, metaplasia and carcinoma. One of the most common types of endometrial metaplasia is ciliated tubal metaplasia. It is generally known that endometrial tubal metaplasia is a benign disease. However studies propose endometrial tubal metaplasia to be a potential premalignant endometrial lesion and its association with endometrial hyperplasia and well-differentiated endometrioid carcinoma. We propose close monitoring of patients taking tamoxifen and prompt evaluation of any uterine bleeding or pelvic complaint or abnormal TVUS images. PMID:26261678

  18. The prevalence of endometrial cancer in pre- and postmenopausal Chinese women.

    PubMed

    Gao, Yifei; Zhao, Min; Dai, Xujing; Tong, Mancy; Wei, Jia; Chen, Qi

    2016-08-01

    The incidence of endometrial cancer depends in part on the ethnicity and geographical area in which the woman resides. Menopause status is a well-known risk factor for endometrial cancer and most cases occur after menopause. It is, however, less clear how the menopause status is associated with endometrial cancer including its subtypes in Chinese women. Data on 1,746 women with endometrial cancer including age at diagnosis, age at menopause, and tumor histology from two large obstetrical and gynecological hospitals in China were analyzed. The median age of women at diagnosis was 50 years. Fifty-eight percent of women were diagnosed after menopause. Fifty-six percent of women with type 1 and 69% with type 2 were diagnosed after menopause. In addition, in both pre- and postmenopausal women, there was no difference in the age at diagnosis between type 1 (46 vs 46 y) and type 2 endometrial cancer (53 vs 52 y). Our data demonstrate that although both type 1 and type 2 endometrial cancers are more likely to occur in Chinese women after menopause than before, the total prevalence of endometrial cancer is lower in our study population than in previous reports from white women (80%). The age at diagnosis did not differ between type 1 and type 2 endometrial cancers regardless of the menopause status in our study population. Our results caution clinicians to be more aware of the importance of abnormal uterine bleeding in premenopausal Chinese women.

  19. Analysis of endometrial thickness measured by transvaginal ultrasonography in obese patients

    PubMed Central

    Barboza, Isabela Corrêa; Depes, Daniella de Batista; Vianna, Ilzo; Patriarca, Marisa Teresinha; Arruda, Raquel Martins; Martins, João Alfredo; Lopes, Reginaldo Guedes Coelho

    2014-01-01

    ABSTRACT Objective To compare the endometrial echo values obtained by transvaginal ultrasonography with the body mass index of postmenopausal patients; to verify if there is higher prevalence of endometrial thickening in women with body mass index ≥30. Methods This is an analytical and cross-sectional study that evaluated 294 patients. Postmenopausal women were included, and those on hormone therapy were excluded. The variables evaluated were body mass index (considering obesity if >30), number of pregnancies, years since menopause, and age. These variables were correlated with endometrial echography. Results There was a statistically significant correlation between overweight and obese patients and increased endometrial thickness (p=0.0236). The correlation between age and endometrial echo was negative and statistically significant, that is, the older the woman, the lower the endometrial thickness (p=0.0478). Pregnancies and years since menopause showed no statistical significance in relation to endometrial echo, with p=0.0614 and p=0.115, respectively. Conclusion There was positive and significant correlation between body mass index ≥30 and endometrial thickeness. PMID:25003920

  20. Recent Changes in Endometrial Cancer Trends Among Menopausal-Age US Women

    PubMed Central

    Wartko, Paige; Sherman, Mark E; Yang, Hannah P; Felix, Ashley S; Brinton, Louise A; Trabert, Britton

    2013-01-01

    Background Changes in endometrial cancer incidence rates after the precipitous decline in menopausal hormone therapy (MHT) use in 2002 have not been evaluated. Methods Using data from the Surveillance, Epidemiology, and End Results Program from 1992–2009 (SEER 13), we identified 63,428 incident endometrial cancer cases among women ages 20–74. We compared Annual Percent Change (APC) in endometrial cancer incidence rates from 1992–2002 to rates from 2003–2009. Results In contrast to the constant endometrial cancer rate pattern observed from 1992–2002 (APC 0.0%), rates increased after 2002 in women 50–74 years old (2.5%; PAPC comparison <0.01). Endometrial cancer incidence increased over the entire time period among women ages 20–49 (1992–2002: 1.1%; 2003–2009: 2.1%; PAPC comparison = 0.21). Post-2002 increases in incidence among women ages 50–74 were specific to Type I endometrial tumors (1992–2002: −0.6%; 2003–2009: 1.6%; PAPC comparison < 0.01). Discussion The increase in endometrial cancer incidence rates after 2002 may be related to the widespread decrease in estrogen plus progestin MHT use, which has been reported to lower endometrial cancer risk in overweight and obese women. PMID:23591011

  1. Endometrial carcinoma located in the right septate uterus cavity: a case report

    PubMed Central

    Boubess, Ikram; Mahdi, Youssef; Ramsiss, Hanan; Filali, Adib; Alami, Mohamad Hassan; El khannoussi, Basma; Hachi, Hafid

    2015-01-01

    Endometrial cancer in patients with uterine congenital malformations is exceptional and there are only a few rare cases published in the literature. We report the case of a 67 years-old patient with an endometrial cancer located in the right cavity of a complete septate uterus. PMID:26958135

  2. Overactive mTOR signaling leads to endometrial hyperplasia in aged women and mice.

    PubMed

    Bajwa, Preety; Nielsen, Sarah; Lombard, Janine M; Rassam, Loui; Nahar, Pravin; Rueda, Bo R; Wilkinson, J Erby; Miller, Richard A; Tanwar, Pradeep S

    2017-01-31

    During aging, uncontrolled epithelial cell proliferation in the uterus results in endometrial hyperplasia and/or cancer development. The mTOR signaling pathway is one of the major regulators of aging as suppression of this pathway prolongs lifespan in model organisms. Genetic alterations in this pathway via mutations and/or amplifications are often encountered in endometrial cancers. However, the exact contribution of mTOR signaling and uterine aging to endometrial pathologies is currently unclear. This study examined the role of mTOR signaling in uterine aging and its implications in the development of endometrial hyperplasia. The hyperplastic endometrium of both postmenopausal women and aged mice exhibited elevated mTOR activity as seen with increased expression of the pS6 protein. Analysis of uteri from Pten heterozygous and Pten overexpressing mice further confirmed that over-activation of mTOR signaling leads to endometrial hyperplasia. Pharmacological inhibition of mTOR signaling using rapamycin treatment suppressed endometrial hyperplasia in aged mice. Furthermore, treatment with mTOR inhibitors reduced colony size and proliferation of a PTEN negative endometrial cancer cell line in 3D culture. Collectively, this study suggests that hyperactivation of the mTOR pathway is involved in the development of endometrial hyperplasia in aged women and mice.

  3. Endometrial carcinoma located in the right septate uterus cavity: a case report.

    PubMed

    Boubess, Ikram; Mahdi, Youssef; Ramsiss, Hanan; Filali, Adib; Alami, Mohamad Hassan; El Khannoussi, Basma; Hachi, Hafid

    2015-01-01

    Endometrial cancer in patients with uterine congenital malformations is exceptional and there are only a few rare cases published in the literature. We report the case of a 67 years-old patient with an endometrial cancer located in the right cavity of a complete septate uterus.

  4. 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

    2017-01-31

    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

  5. P53 and Murine Double Mimute 2 (MDM2) Expression Changes and Significance in Different Types of Endometrial Lesions

    PubMed Central

    Jiang, Zhongyong; Xu, Wanqing; Dan, Gang; Liu, Yuan; Xiong, Jie

    2016-01-01

    Background Endometrial lesions are common in obstetrics and gynecology, including endometrial polyps, uterine adenomyosis, and malignant endometrial adenocarcinoma. Endometrial lesions seriously affect women’s health, fertility, quality of life, and life safety. As a pro-apoptosis gene, p53 is considered to be closely related with human tumors. Murine double mimute 2 (MDM2) is an oncogene that can promote tumor occurrence and development. P53 and MDM2 expression and significance in different types of endometrial lesions have not been fully elucidated. Material/Methods Normal endometrium, endometrial polyps, uterine adenomyosis, and endometrial adenocarcinoma tissue samples were collected. Real-time PCR was used to detect p53 and MDM2 mRNA expression. Immunohistochemical staining and Western blot analysis were applied to test p53 and MDM2 protein expression. Their correlation with clinical staging of endometrial adenocarcinoma was analyzed. Results P53 and MDM2 mRNA and protein expression were significantly elevated in the endometrial polyps group and the endometrial adenocarcinoma group compared with the normal control group (P<0.05). Their levels increased more obviously in endometrial adenocarcinoma compared with endometrial polyps (P<0.05). P53 and MDM2 mRNA and protein expression were slightly enhanced in uterine adenomyosis compared with normal controls, but this difference lacked statistical significance (P>0.05). P53 and MDM2 mRNA and protein level showed a positive correlation. Significantly higher expression of p53 or MDM2 was observed in patients with stage III compared to those in patients with stage II. Higher expression was also observed in patients with stage II than in patients with stage I. Conclusions P53 and MDM2 mRNA and protein were elevated in endometrial polyps and endometrial adenocarcinoma and their expressions were correlated with clinical staging of endometrial adenocarcinoma. They can promote cancer occurrence and development, and can

  6. Comparison of Pipelle sampler with conventional dilatation and curettage (D&C) for Chinese endometrial biopsy.

    PubMed

    Liu, H; Wang, F-L; Zhao, Y-M; Yao, Y-Q; Li, Y-L

    2015-01-01

    The aim of this study is to investigate the accuracy and adequacy of the Pipelle endometrial sampler for endometrial biopsy as compared with those of conventional dilatation and curettage (D&C). A total of 245 patients subject to endometrial biopsy were included in this study. We have shown that the failure rates with D&C and Pipelle were 7.75% and 8.98%, respectively, without statistical difference. Additionally, the obtained specimen quality and accurate diagnosis of various diseases using the two methods had no significant statistical differences. Furthermore, patients experienced less pain when Pipelle sampler was used than D&C. Therefore, Pipelle sampler is effective in obtaining adequate endometrial tissue for histodiagnosis, and is applicable in most of the cases for Chinese endometrial biopsy.

  7. Immunohistochemical analysis of ras oncogene product p21 in human endometrial carcinoma.

    PubMed

    Yaginuma, Y; Fujita, M; Saitoh, S; Hayakawa, K; Kuzumaki, N; Ishikawa, M

    1993-09-01

    Monoclonal antibody rp-28 directed against the ras gene product p21 has been used to evaluate ras p21 expression in endometrial lesions. Endometrial cancer showed a variable reactivity according to histological type: in well differentiated adenocarcinoma 63% were positive (12/19); in moderately differentiated adenocarcinoma 53% were positive (8/15); in poorly differentiated adenocarcinoma 40% were positive (2/5). The staining intensity of ras p21 seemed to be stronger in the more differentiated types of endometrial carcinoma. In endometrial carcinoma with premenopausal women, 27% were positive (3/11), and with postmenopausal women 71% were positive (20/28). The difference between premenopausal and postmenopausal groups was statistically significant (Mantel-Haenszel procedure, M-H chi 2 = 6.765, P < 0.01). The results suggest the existence of different carcinogenetic mechanisms in these two groups of endometrial cancer.

  8. Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment.

    PubMed

    Onstad, Michaela A; Schmandt, Rosemarie E; Lu, Karen H

    2016-12-10

    In sharp contrast to many other cancer types, the incidence and mortality of endometrial cancer continue to grow. This unfortunate trend is, in no small part, a result of the worldwide obesity epidemic. More than half of endometrial cancers are currently attributable to obesity, which is recognized as an independent risk factor for this disease. In this review, we identify the molecular mechanisms by which obesity and adipose tissue contribute to the pathogenesis of endometrial cancer. We further discuss the impact of obesity on the clinical management of the disease and examine the development of rational behavioral and pharmaceutical interventions aimed at reducing endometrial cancer risk, improving cancer outcomes, and preserving fertility in an increasingly younger population of patients with endometrial cancer.

  9. 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.

  10. Addressing the Role of Obesity in Endometrial Cancer Risk, Prevention, and Treatment

    PubMed Central

    Onstad, Michaela A.; Schmandt, Rosemarie E.

    2016-01-01

    In sharp contrast to many other cancer types, the incidence and mortality of endometrial cancer continue to grow. This unfortunate trend is, in no small part, a result of the worldwide obesity epidemic. More than half of endometrial cancers are currently attributable to obesity, which is recognized as an independent risk factor for this disease. In this review, we identify the molecular mechanisms by which obesity and adipose tissue contribute to the pathogenesis of endometrial cancer. We further discuss the impact of obesity on the clinical management of the disease and examine the development of rational behavioral and pharmaceutical interventions aimed at reducing endometrial cancer risk, improving cancer outcomes, and preserving fertility in an increasingly younger population of patients with endometrial cancer. PMID:27903150

  11. 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

  12. A study of the influence of a gestodene-containing triphasic oral contraceptive on endometrial morphology.

    PubMed

    Rabe, T; Leppien, G; Fossman, W G; Hessing, C; Vladescú, E; Runnebaum, B

    1997-09-01

    The objective of the study was to investigate histological changes in the endometrium in 20 volunteers treated with a low-dose, gestodene-containing triphasic oral contraceptive. Endometrial biopsy specimens were taken before, during a 6-month period of oral contraceptive use and in a post-treatment period. These specimens were evaluated using light microscopy, scanning and transmission electron microscopy. In addition, ultrasound examinations of the uterus, endometrial thickness and ovaries were performed. The low-dose, gestodene-containing triphasic oral contraceptive had no adverse effects on the endometrium (e.g. no proliferation, no polyps, no inflammatory processes), was well tolerated and showed a low side-effect profile. The inhibition of endometrial transformation was demonstrated both by endometrial morphology as well as by endometrial thickness, as measured by transvaginal ultrasound examination.

  13. Critical tumor suppressor function mediated by epithelial Mig-6 in endometrial cancer.

    PubMed

    Kim, Tae Hoon; Lee, Dong-Kee; Cho, Sung-Nam; Orvis, Grant D; Behringer, Richard R; Lydon, John P; Ku, Bon Jeong; McCampbell, Adrienne S; Broaddus, Russell R; Jeong, Jae-Wook

    2013-08-15

    Endometrial cancer is preceded by endometrial hyperplasia, unopposed estrogen exposure, and genetic alterations, but the precise causes of endometrial cancer remain uncertain. Mig-6, mainly known as a negative regulator of the EGF receptor, is an important mediator of progesterone signaling in the uterus, where it mediates tumor suppression by modulating endometrial stromal-epithelial communications. In this study, we investigated the function of Mig-6 in the uterine epithelium using a tissue-specific gene knockout strategy, in which floxed Mig-6 (Mig-6(f/f)) mice were crossed to Wnt7a-Cre mice (Wnt7a(cre+)Mig-6(f/f)). Wnt7a(cre+)Mig-6(f/f) mice developed endometrial hyperplasia and estrogen-dependent endometrial cancer, exhibiting increased proliferation in epithelial cells as well as apoptosis in subepithelial stromal cells. We documented increased expression of NOTCH1 and BIRC3 in epithelial cells of Wnt7a(cre+)Mig-6(f/f) mice and decreased expression of the progesterone receptor (PR) in stromal cells. Progesterone therapy controls endometrial growth and prevents endometrial cancer, but the effectiveness of progesterone as a treatment for women with endometrial cancer is less clear. We noted that the hyperplasic phenotype of Wnt7a(cre+)Mig-6(f/f) mice was prevented by progesterone treatment, whereas this treatment had no effect in PR(cre/+)Mig-6(f/f) mice where Mig-6 was deleted in both the epithelial and stromal compartments of the uterus. In contrast, activation of progesterone signaling in the stroma regulated proliferation and apoptosis in the epithelium via suppression of ERα signaling. In summary, our results establish that epithelial Mig-6 functions as a critical tumor suppressor that mediates the ability of progesterone to prevent the development of endometrial cancer.

  14. Critical tumor suppressor function mediated by epithelial Mig-6 in endometrial cancer

    PubMed Central

    Kim, Tae Hoon; Lee, Dong-Kee; Cho, Sung-Nam; Orvis, Grant D.; Behringer, Richard R.; Lydon, John P.; Ku, Bon Jeong; McCampbell, Adrienne S.; Broaddus, Russell R.; Jeong, Jae-Wook

    2013-01-01

    Endometrial cancer is preceded by endometrial hyperplasia, unopposed estrogen exposure and genetic alterations, but the precise causes of endometrial cancer remain uncertain. Mig-6, mainly known as a negative regulator of the EGF receptor, is an important mediator of progesterone signaling in the uterus, where it mediates tumor suppression by modulating endometrial stromal-epithelial communications. In this study, we investigated the function of Mig-6 in the uterine epithelium using a tissue-specific gene knockout strategy, in which floxed Mig-6 (Mig-6f/f) mice were crossed to Wnt7a-Cre mice (Wnt7acre+ Mig-6f/f). Wnt7acre+ Mig-6f/f mice developed endometrial hyperplasia and estrogen-dependent endometrial cancer, exhibiting increased proliferation in epithelial cells as well as apoptosis in sub-epithelial stromal cells. We documented increased expression of NOTCH1 and BIRC3 in epithelial cells of Wnt7acre+ Mig-6f/f mice and decreased expression of the progesterone receptor (PR) in stromal cells. Progesterone therapy controls endometrial growth and prevents endometrial cancer, but the effectiveness of progesterone as a treatment for women with endometrial cancer is less clear. We noted that the hyperplasic phenotype of Wnt7acre+ Mig-6f/f mice was prevented by progesterone treatment, whereas this treatment had no effect in PRcre/+ Mig-6f/f mice where Mig-6 was deleted in both the epithelial and stromal compartments of the uterus. In contrast, activation of progesterone signaling in the stroma regulated proliferation and apoptosis in the epithelium via suppression of ERα signaling there. In summary, our results establish that epithelial Mig-6 functions as a critical tumor suppressor that mediates the ability of progesterone to prevent the development of endometrial cancer. PMID:23811943

  15. Angiotensin II type I receptor and miR-155 in endometrial cancers: synergistic antiproliferative effects of anti-miR-155 and losartan on endometrial cancer cells.

    PubMed

    Choi, Chel Hun; Park, Young-Ae; Choi, Jung-Joo; Song, Taejong; Song, Sang Yong; Lee, Yoo-Young; Lee, Jeong-Won; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

    2012-07-01

    MicroRNA-155 (miR-155) is one of the micro RNAs (miRNA) most consistently involved in neoplastic diseases, and it is known to repress the angiotensin II type 1 receptor (AGTR1). The aim of the present study was to evaluate the expressions of miR-155 and AGTR1, and to clarify the potential efficacy of anti-miR-155, alone and in combination with AGTR1 blocker losartan in endometrial cancers. Expressions of miR-155 and AGTR1 were evaluated using real-time PCR and immunohistochemistry. And the MTT assay was performed in endometrial cancer cells following anti-miR-155 and AGTR1 blocker (losartan) treatment, alone and in combination. miR-155 was over-expressed and AGTR1 was underexpressed in endometrial carcinoma tissues. AGTR1 immunoreactivity was found in six of ten (60.0%) normal endometrium, 11 of 14 (78.6%) endometrial hyperplasia, and 27 of 62 (43.5%) endometrial carcinoma tissues (P=0.051), and patients with AGTR1 expression showed trend towards improved survival after multivariate analysis (P=0.08). We checked that abolishing the function of miR-155 and AGTR1 by anti-miR-155 or losartan inhibited cell survival of endometrial carcinoma cells, respectively, and furthermore, combined treatment showed synergistic effects. In this study, we characterized the expressions of miR-155 and AGTR1 in endometrial tissues. The combined treatment with anti-miR-155 and losartan has a synergistic antiproliferative effect and an improved understanding is required to clarify whether miR-155 and AGTR1 can be used as a novel therapeutic target in endometrial cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. 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

  17. 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.

  18. Endometrial receptivity: expression of alpha3beta1, alpha4beta1 and alphaVbeta1 endometrial integrins in women with impaired fertility.

    PubMed

    Skrzypczak, J; Mikołajczyk, M; Szymanowski, K

    2001-11-01

    Advances in immunohistochemical methods with the specificity of poly- and monoclonal antibodies allow the description of the endometrial receptivity, which is characterized by the ability of secretion of phase specific proteins and glikoproteins by epithelial and stromal cells. We studied the differences in the expression of alpha3beta1, alpha4beta1 and alphaVbeta1 integrins in endometrium of women with recurrent miscarriages and women with unexplained infertility. The endometrial tissue was collected during hysteroscopy performed between 7th and 9th day after ovulation. The immunohistochemical evaluation of alpha3beta1, alpha4beta1 and alphaVbeta1 integrin expression was determined in all endometrial biopsies. Staining intensity of alpha3beta1 in glandular epithelium and endometrial stroma was similar in both groups. In women with recurrent miscarriages we noted a lower concentrations of the alpha4beta1 and alphaVbeta1 integrins during the midluteal phase than in women with unexplained infertility. Moreover, integrins alpha4beta1 and alphaVbeta1 were expressed more frequently in glandular epithelium and endometrial stroma of women with unexplained infertility than those of women with recurrent miscarriages. However, alphaV(2)1 staining in endometrial stroma was stronger than that of alpha4beta1. It can be concluded, that these integrins may play an important role in the implantation process.

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

    PubMed Central

    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

    2016-01-01

    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. PMID:27754426

  20. Adjuvant hormonal therapy for stage I endometrial cancer.

    PubMed

    Gien, L; Kwon, J; Oliver, T K; Fung-Kee-Fung, M

    2008-06-01

    What is the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer? There is little consensus on the role of adjuvant treatment for patients with stage i endometrial cancer. Although the use of hormonal therapy has been established in advanced disease, less agreement has emerged concerning the benefits of adjuvant hormonal therapy for patients with early-stage disease. The objective of the present evidence series was to review the existing literature on the role of hormonal therapy as adjuvant therapy in patients with stage i endometrial cancer. REPORTS WERE SOUGHT THAT INCLUDED AT LEAST ONE OF THE FOLLOWING OUTCOMES: overall survival, disease-free survival, recurrence (local, or distant, or both), adverse effects, and quality of life. Because of the potential for long-term adverse effects with adjuvant hormonal treatment in this patient population, especially with regard to thromboembolic or cardiovascular events, the rates of non-cancer-related death were also of interest. The medline, embase, and Cochrane Library databases were systematically searched for randomized controlled trials, practice guidelines, systematic reviews, and meta-analyses. The resulting evidence informed the development of the clinical practice guideline. The systematic review with meta-analyses and practice guideline were approved by the Report Approval Panel of the Program in Evidence-Based Care, and by the Gynecology Cancer Disease Site Group (DSG). Nine randomized trials and one published meta-analysis comparing adjuvant hormonal therapy with no adjuvant therapy in women with stage i endometrial cancer constituted the evidence base. One trial reported a statistically significant survival benefit with adjuvant progestogen as compared with no further treatment (97% vs. 69%, p < 0.001). In that trial, the treatment group had a higher number of patients with less myometrial invasion, and a lower number of patients with advanced-stage disease. These

  1. Endometrial cancer survival after breast cancer in relation to tamoxifen treatment: Pooled results from three countries

    PubMed Central

    2012-01-01

    Introduction Tamoxifen is an effective treatment for breast cancer but an undesirable side-effect is an increased risk of endometrial cancer, particularly rare tumor types associated with poor prognosis. We investigated whether tamoxifen therapy increases mortality among breast cancer patients subsequently diagnosed with endometrial cancer. Methods We pooled case-patient data from the three largest case-control studies of tamoxifen in relation to endometrial cancer after breast cancer (1,875 patients: Netherlands, 765; United Kingdom, 786; United States, 324) and collected follow-up information on vital status. Breast cancers were diagnosed in 1972 to 2005 with endometrial cancers diagnosed in 1978 to 2006. We used Cox proportional hazards survival analysis to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results A total of 1,104 deaths occurred during, on average, 5.8 years following endometrial cancer (32% attributed to breast cancer, 25% to endometrial cancer). Mortality from endometrial cancer increased significantly with unfavorable non-endometrioid morphologies (P < 0.0001), International Federation of Gynaecology and Obstetrics staging system for gynecological malignancy (FIGO) stage (P < 0.0001) and age (P < 0.0001). No overall association was observed between tamoxifen treatment and endometrial cancer mortality (HR = 1.17 (95% CI: (0.89 to 1.55)). Tamoxifen use for at least five years was associated with increased endometrial cancer mortality (HR = 1.59 (1.13 to 2.25)). This association appeared to be due primarily to the excess of unfavorable histologies and advanced stage in women using tamoxifen for five or more years since the association with mortality was no longer significant after adjustment for morphological type and FIGO stage (HR = 1.37 (0.97 to 1.93)). Those patients with endometrioid tumors, who stopped tamoxifen use at least five years before their endometrial cancer diagnosis, had a greater mortality risk from endometrial

  2. 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.

  3. Distribution of estrogen and progesterone receptors isoforms in endometrial cancer

    PubMed Central

    2014-01-01

    Background 70–80% of sporadic endometrial carcinomas are defined as endometrioid carcinoma (EC). Early-stage, well differentiated endometrial carcinomas usually retain expression of estrogen and progesterone receptors (ER and PR, respectively), as advanced stage, poorly differentiated tumors often lack one or both of these receptors. Well-described EC prognosis includes tumor characteristics, such as depth of myometrial invasion. Therefore, in the current study, we evaluated the expression profile of ER and PR isoforms, including ER-α, PR-A and PR–B, in correlation to EC tumor histological depth. Methods Using immunohistochemistry and image analysis software, the expression of ER-α, PR-A, PR–B and Ki67 was assessed in endometrial stroma and epithelial glands of superficial, deep and extra-tumoral sections of 15 paraffin embedded EC specimens, and compared to 5 biopsies of non-malignant endometrium. Results Expression of PR-A and ER-α was found to be lower in EC compared to nonmalignant tissue, as the stromal expression was dramatically reduced compared to epithelial cells. Expression ratios of both receptors were significantly high in superficial and deep portions of EC; in non-tumoral portion of EC were close to the ratios of nonmalignant endometrium. PR-B expression was low in epithelial glands of EC superficial and deep portions, and high in the extra-tumoral region. Elevated PR-B expression was found in stroma of EC, as well. Conclusions The ratio of ER-α and PR-A expression in the epithelial glands and the stroma of EC biopsies may serve as an additional parameter in the histological evaluation of EC tumor. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1155060506119016 PMID:24684970

  4. Photoaffinity labeling of the progesterone receptor from human endometrial carcinoma

    SciTech Connect

    Clarke, C.L.; Satyaswaroop, P.G.

    1985-11-01

    A nude mouse model for the growth of human endometrial carcinoma and hormonal modulation of the progesterone receptor (PR) was established previously. This study describes the effect of 17 beta-estradiol and tamoxifen (TAM) on growth rate and PR concentration in a hormonally responsive human endometrial tumor (EnCa 101) grown in this experimental system and presents the first characterization of human endometrial carcinoma PR. EnCa 101 was transplanted subcutaneously into ovariectomized, BALB/c, nu/nu athymic mice and grown under 17 beta-estradiol-stimulated, TAM-stimulated, and control conditions. Both 17 beta-estradiol and TAM increased the growth rate of EnCa 101 in nude mice, and a parallel increase in the cytosol PR concentration was observed. PR was partially purified by phosphocellulose and DEAE cellulose chromatography, and the DEAE eluate was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and photoaffinity labeling with (17 alpha-methyl-TH)promegestone ((TH)R5020). Two PR-negative tumors (EnCa K and EnCa V) were also examined in parallel. Photolabeling and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of EnCa 101 grown in the presence of 17 beta-estradiol or TAM revealed incorporation of (3H)R5020 into proteins of molecular weight approximately 116,000 and 85,000. Labeled proteins of molecular weight 66,000, 45,000, and 35,000 were also observed. No incorporation of (TH)R5020 was observed in EnCa 101 grown in the absence of estrogen, nor was any observed in EnCa K or EnCa V.

  5. Rac1 Regulates Endometrial Secretory Function to Control Placental Development

    PubMed Central

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

    2015-01-01

    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

  6. Lymphovascular space invasion in robotic surgery for endometrial cancer.

    PubMed

    Hopkins, Mark R; Richmond, Abby M; Cheng, Georgina; Davidson, Susan; Spillman, Monique A; Sheeder, Jeanelle; Post, Miriam D; Guntupalli, Saketh R

    2014-01-01

    Minimally invasive surgery has become a standard treatment for endometrial cancer and offers significant benefits over abdominal approaches. There are discrepant data regarding lymphovascular space invasion (LVSI) and positive peritoneal cytology with the use of a uterine manipulator, with previous small-scale studies demonstrating an increased incidence of these prognostically important events. We sought to determine if there was a higher incidence of LVSI in patients who underwent robot-assisted surgery for endometrial cancer. We performed a single-institution review of medical records for patients who underwent open abdominal or robot-assisted hysterectomy for endometrial cancer over a 24-month period. The following data were abstracted: age, tumor grade and stage, size, depth of invasion, LVSI, and peritoneal cytology. For patients with LVSI, slides were reviewed by 2 pathologists for confirmation of LVSI. Of 104 patients identified, LVSI was reported in 39 (37.5%) and positive peritoneal cytology in 6 (4.8%). Rates of peritoneal cytology were not significantly different between the 2 groups (odds ratio, 0.55; 95% confidence interval, 0.10-3.17; P=.50). LVSI was reported in significantly fewer robot-assisted hysterectomies than open procedures (odds ratio, 0.39; 95% confidence interval, 0.17-0.92; P=.03). In subgroup analyses restricted to early-stage disease (stage≤II), there was no significant difference in LVSI between open and robot-assisted hysterectomies (odds ratio, 0.64; 95% confidence interval, 0.22-1.85; P=.43). In this retrospective study, we found that use of a uterine manipulator in robot-assisted surgery did not increase the incidence of LVSI.

  7. Odds ratio analysis in women with endometrial cancer

    PubMed Central

    Żak, Ewa; Pięta, Beata

    2016-01-01

    Introduction Despite the progress in diagnosis and treatment of malignant tumours, the effects of treatment are insufficient. Reduction of the risk of cervical, ovarian, and endometrial cancer is possible by introducing preventative actions. Aim of the study The aim of the thesis is the analysis of selected risk factors that may affect the increase or decrease in the odds ratio of developing endometrial cancer. Material and methods The study was conducted among patients of the Gynaecology and Obstetrics Hospital of Poznań University of Medical Sciences in the years 2011-2013. The research included a total of 548 female respondents aged between 40 and 84 years. Women responded to questions assessing elements of lifestyle such as consumption of alcohol, smoking, and eating certain groups of foods. Results The respondents consuming fruits and vegetables several times a week have a reduced risk of odds ratio and the OR is 0.85; 95% CI: 0.18-4.09, compared to the women who rarely consume vegetables and fruits. Consumption of whole-wheat bread several times a week reduces the risk of developing the cancer, OR = 0.59; 95% CI: 0.14-2.47, compared to women not consuming wholegrain bread at all. Respondents who consumed red meat, such as veal, pork, and lamb in the amount of 101-200 g per day have an increased risk of developing the disease: OR = 2.16; 95% CI: 1.09-4.28, compared to women not consuming red meat at all. Conclusions A diet rich in fruit and vegetables, onions, garlic, whole grains, and beans should be introduced in order to reduce the risk of endometrial cancer. The consumption of red meat and white pasta should be reduced or even eliminated. PMID:27095953

  8. Endometrial Stromal Decidualization Responds Reversibly to Hormone Stimulation and Withdrawal

    PubMed Central

    Yu, Jie; Berga, Sarah L.; Johnston-MacAnanny, Erika B.; Sidell, Neil; Bagchi, Indrani C.; Bagchi, Milan K.

    2016-01-01

    Human endometrial stromal decidualization is required for embryo receptivity, angiogenesis, and placentation. Previous studies from our laboratories established that connexin (Cx)-43 critically regulates endometrial stromal cell (ESC) differentiation, whereas gap junction blockade prevents it. The current study evaluated the plasticity of ESC morphology and Cx43 expression, as well as other biochemical markers of cell differentiation, in response to decidualizing hormones. Primary human ESC cultures were exposed to 10 nM estradiol, 100 nM progesterone, and 0.5 mM cAMP for up to 14 days, followed by hormone withdrawal for 14 days, mimicking a biphasic ovulatory cycle. Reversible differentiation was documented by characteristic changes in cell shape. Cx43 was reversibly up- and down-regulated after the estradiol, progesterone, and cAMP treatment and withdrawal, respectively, paralleled by fluctuations in prolactin, vascular endothelial growth factor, IL-11, and glycodelin secretion. Markers of mesenchymal-epithelial transition (MET), and its counterpart epithelial-mesenchymal transition, followed reciprocal patterns corresponding to the morphological changes. Incubation in the presence of 18α-glycyrrhetinic acid, an inhibitor of gap junctions, partially reversed the expression of decidualization and MET markers. In the absence of hormones, Cx43 overexpression promoted increases in vascular endothelial growth factor and IL-11 secretion, up-regulated MET markers, and reduced N-cadherin, an epithelial-mesenchymal transition marker. The combined results support the hypothesis that Cx43-containing gap junctions and endocrine factors cooperate to regulate selected biomarkers of stromal decidualization and MET and suggest roles for both phenomena in endometrial preparation for embryonic receptivity. PMID:27035651

  9. Methylation profiles of endometrioid and serous endometrial cancers.

    PubMed

    Seeber, Laura M S; Zweemer, Ronald P; Marchionni, Luigi; Massuger, Leon F A G; Smit, Vincent T H B M; van Baal, W Marchien; Verheijen, René H M; van Diest, Paul J

    2010-09-01

    Promoter methylation is a gene- and cancer type-specific epigenetic event that plays an important role in tumour development. As endometrioid (endometrioid endometrial carcinoma, EEC) and serous endometrial cancers (uterine papillary serous carcinoma, UPSC) exhibit different clinical, histological and molecular genetic characteristics, we hypothesized that these differences may be reflected in epigenetic phenomena as well. Identification of a panel of methylation biomarkers could be helpful in a correct histological classification of these two subtypes, which solely on the basis of morphology is not always easy. Methylation-specific multiplex ligation-dependent probe amplification was used to assess the extent of promoter methylation of different tumour suppressor genes in EEC and UPSC. Methylation results were correlated with histology and survival. The median cumulative methylation index of all genes was significantly higher in EEC (124) than in UPSC (93) (P<0.001). Promoter methylation of CDH13 and MLH1 was more frequently present in EEC, while CDKN2B and TP73 were more frequently methylated in UPSC. Almost 90% of EEC and 70% of UPSC could be predicted by CDH13 and TP73. In EEC, methylation of MLH1 was associated with a shorter disease-free survival (DFS; P<0.0001) and overall survival (OS; P=0.005). In a multivariate model, MLH1 methylation emerged as an additional prognostic factor to stage for DFS (P=0.002). In conclusion, promoter methylation is more common in EEC than UPSC. A panel of methylation biomarkers could be useful to distinguish between the two histological subtypes of endometrial cancer. Furthermore, methylation of MLH1 may have prognostic value in EEC.

  10. Postoperative Lower Extremity Edema in Patients with Primary Endometrial Cancer.

    PubMed

    Bae, Hyo Sook; Lim, Myong Cheol; Lee, Jeong Seon; Lee, Yumi; Nam, Byung Ho; Seo, Sang-Soo; Kang, Sokbom; Chung, Seung Hyun; Kim, Joo-Young; Park, Sang-Yoon

    2016-01-01

    The goal of this study was to investigate clinical manifestations of lower extremity edema (LEE) after lymph node dissection in patients with primary endometrial cancer. Women with primary endometrial cancer who underwent staging surgery between November 2001 and March 2011 were included in the study. Medical records and/or responses to the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) were used for LEE evaluation. All 154 patients underwent pelvic lymph node dissection, and 126 patients (81.8 %) underwent paraaortic LN dissection. The median age of the patients was 52 years, the majority had stage I cancer (78.6 %), and most had endometrioid histology (90.9 %). The most frequent GCLQ responses were "experienced swelling" (35.7 %), "experienced numbness" (30.5 %), "experienced heaviness" (29.9 %), and "experienced aching" (29.9 %). Sixty-four patients (41.6 %) had previous (9/64, 14.1 %) and/or current (55/64, 85.9 %) patient-reported LEE. Most patients developed LEE within 12 months after surgery (39/56, 69.6 %), and LEE lasted for more than 12 months in most patients (45/56, 80.4 %). Three patients reported recurrent LEE after recovery. Multivariate logistic regression identified the number of dissected pelvic lymph node (≥21) as a risk factor for LEE [odds ratio (OR) 3.28; 95 % confidence interval (CI) 1.058-10.136] and postoperative radiotherapy (OR 3.81, 95 % CI 1.67-8.69). LEE developed in more than one-third of patients with endometrial cancer after surgery, and LEE lasted for more than 12 months in most patients. A high number of dissected pelvic lymph nodes and postoperative radiotherapy is associated with LEE.

  11. Karyometry in atypical endometrial hyperplasia: a Gynecologic Oncology Group study.

    PubMed

    Bartels, Peter H; Garcia, Francisco A R; Trimble, Cornelia L; Kauderer, James; Curtin, John; Lim, Peter C; Hess, Lisa M; Silverberg, Steven; Zaino, Richard J; Yozwiak, Michael; Bartels, Hubert G; Alberts, David S

    2012-04-01

    Treatment for atypical endometrial hyperplasia (AEH) is based on pathologic diagnosis. About 40% of AEH is found to be carcinoma at surgery. This study's objective is to derive an objective characterization of nuclei from cases diagnosed as AEH or superficially invasive endometrial cancer (SIEC). Cases from GOG study 167A were classified by a central pathology committee as AEH (n=39) or SIEC (n=39). High resolution digitized images of cell nuclei were recorded. Features of the nuclear chromatin pattern were computed. Classification rules were derived by discriminant analysis. Nuclei from cases of AEH and SIEC occupy the same range on a progression curve for endometrial lesions. Cases of AEH and SIEC both comprise nuclei of two phenotypes: hyperplastic characteristics and premalignant/neoplastic characteristics. The principal difference between AEH and SIEC is the percentage of premalignant/neoplastic nuclei. When this percentage approaches 50-60% superficial invasion is likely. SIEC may develop already from lesions at the low end of the progression curve. AEH comprises cases which may constitute a low risk group involving <40% of AEH cases. These cases hold a percentage of <20% of nuclei of a preneoplastic phenotype. AEH cases from the central and high end of progression have >40% of nuclei of preneoplastic phenotype. Nuclei of the preneoplastic phenotype in AEH lesions are almost indistinguishable from nuclei in SIEC, where this percentage exceeds 60%. The percentage of nuclei of the preneoplastic phenotype in AEH esions might serve as criterion for assessment of risk for the development of invasive disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Karyometry in atypical endometrial hyperplasia: A Gynecologic Oncology Group study

    PubMed Central

    Bartels, Peter H; Garcia, Francisco AR; Trimble, Cornelia L; Kauderer, James; Curtin, John; Lim, Peter C; Hess, Lisa M; Silverberg, Steven; Zaino, Richard J; Yozwiak, Michael; Bartels, Hubert G; Alberts, David S

    2014-01-01

    Objectives Treatment for atypical endometrial hyperplasia (AEH) is based on pathologic diagnosis. About 40% of AEH is found to be carcinoma at surgery. This study's objective is to derive an objective characterization of nuclei from cases diagnosed as AEH or superficially invasive endometrial cancer (SIEC). Methods Cases from GOG study 167A were classified by a central pathology committee as AEH (n=39) or SIEC (n=39). High resolution digitized images of cell nuclei were recorded. Features of the nuclear chromatin pattern were computed. Classification rules were derived by discriminant analysis. Results Nuclei from cases of AEH and SIEC occupy the same range on a progression curve for endometrial lesions. Cases of AEH and SIEC both comprise nuclei of two phenotypes: hyperplastic characteristics and premalignant/neoplastic characteristics. The principal difference between AEH and SIEC is percentage of premalignant/neoplastic nuclei. When this percentage approaches 50-60% superficial invasion is likely. SIEC may develop already from lesions at the low end of the progression curve. Conclusions AEH comprises cases which may constitute a low risk group involving <40% of AEH cases. These cases hold a percentage of <20% of nuclei of a preneoplastic phenotype. AEH cases from the central and high end of progression have >40 % of nuclei of preneoplastic phenotype. Nuclei of the preneoplastic phenotype in AEH lesions are almost indistinguishable from nuclei in SIEC, where this percentage exceeds 60%. The percentage of nuclei of the preneoplastic phenotype in AEH lesions might serve as criterion for assessment of risk for the development of invasive disease. PMID:22155796

  13. 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

  14. TP53 Mutational Spectrum in Endometrioid and Serous Endometrial Cancers.

    PubMed

    Schultheis, Anne M; Martelotto, Luciano G; De Filippo, Maria R; Piscuglio, Salvatore; Ng, Charlotte K Y; Hussein, Yaser R; Reis-Filho, Jorge S; Soslow, Robert A; Weigelt, Britta

    2016-07-01

    Endometrial carcinomas (ECs) are heterogeneous at the genetic level. Although TP53 mutations are highly recurrent in serous endometrial carcinomas (SECs), these are also present in a subset of endometrioid endometrial carcinomas (EECs). Here, we sought to define the frequency, pattern, distribution, and type of TP53 somatic mutations in ECs by performing a reanalysis of the publicly available data from The Cancer Genome Atlas (TCGA). A total of 228 EECs (n=186) and SECs (n=42) from the TCGA data set, for which an integrated genomic characterization was performed, were interrogated for the presence and type of TP53 mutations, and for mutations in genes frequently mutated in ECs. TP53 mutations were found in 15% of EECs and 88% of SECs, and in 91% of copy-number-high and 35% of polymerase (DNA directed), epsilon, catalytic subunit (POLE) integrative genomic subtypes. In addition to differences in prevalence, variations in the type and pattern of TP53 mutations were observed between histologic types and between integrative genomic subtypes. TP53 hotspot mutations were significantly more frequently found in SECs (46%) than in EECs (15%). TP53-mutant EECs significantly more frequently harbored a co-occurring PTEN mutation than TP53-mutant SECs. Finally, a subset of TP53-mutant ECs (22%) was found to harbor frameshift or nonsense mutations. Given that nonsense and frameshift TP53 mutations result in distinct p53 immunohistochemical results that require careful interpretation, and that EECs and SECs display different patterns, types, and distributions of TP53 mutations, the use of the TP53/p53 status alone for the differential diagnosis of EECs and SECs may not be sufficient.

  15. 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

  16. Treatment of Endometrial Cancer in Association with Pelvic Organ Prolapse

    PubMed Central

    Vanichtantikul, Asama; Tharavichitkul, Ekkasit; Chitapanarux, Imjai

    2017-01-01

    Background. Uterine malignancy coexistent with pelvic organ prolapse (POP) is uncommon and standardized treatment is not established. The objective of this case study was to highlight the management of endometrial cancer in association with pelvic organ prolapse. Case Report. An 87-year-old woman presented with POP Stage IV combined with endometrioid adenocarcinoma of the uterus: clinical Stage IV B. She had multiple medical conditions including stroke, deep vein thrombosis, and pulmonary embolism. She was treated with radiotherapy and pessary was placed. Conclusion. Genital prolapse with abnormal uterine bleeding requires proper evaluation and management. Concurrent adenocarcinoma and POP can be a difficult clinical situation to treat, and optimum management is controversial.

  17. [Current strategies in radiotherapy for cervical and endometrial carcinoma].

    PubMed

    Titova, V A; Kharchenko, N V; Dobrovol'skaia, N Iu; Kreĭnina, Iu M

    2009-01-01

    We used combinations of taxan-based neoadjuvant and adjuvant full-dose chemotherapy and aggressive combined radiotherapy including clinical target volume extension, increased total dosage, hyperthermia, cryo- and local chemotherapy as radiosensitizers, for treatment of invasive and locally-advanced breast cancer or endometrial carcinoma with poor prognosis. 3D-ultrasound/CT/MRI--based designing of radiotherapy and monitoring of dynamic definition of target volume and "high risk volume" in organs at risk in cases of tumor progression was an indispensable measure. As a result, no local recurrence was reported in 73% for 36 months.

  18. Xanthogranulomatous appendicitis causing an endometrial abscess: radiological findings.

    PubMed

    Altay, Canan; Yavuz, Esra; Egeli, Tufan; Canda, Emre Aras; Sarioglu, Sulen; Secil, Mustafa

    2015-12-01

    Xanthogranulomatous inflammation (XGI) is a rare chronic inflammatory condition most commonly involving the kidneys and gallbladder. The condition is histopathologically characterized by the presence of foamy histiocytes, lymphocytes, and plasma cells. A few reports describing appendicitis caused by XGI have appeared in the English-language literature. However, no study has yet focused on the imaging features of xanthogranulomatous appendicitis (XGA). We present a pathologically confirmed case of XGA with an endometrial abscess; the patient underwent ultrasonography, computed tomography, and magnetic resonance imaging. To the best of our knowledge, this is the first case of XGA with uterine and right adnexal involvement presenting as a complicated pelvic abscess on radiological imaging.

  19. Carcinoma of the cervix with extensive endometrial and myometrial involvement.

    PubMed

    de Jesus, M; Tang, W; Sadjadi, M; Belmonte, A H; Poon, T P

    1990-02-01

    Verrucous carcinoma is a rare variant of epidermoid carcinoma with distinct clinical and histopathologic features. To date, 31 cases have been reported in the cervix. They are typically slow-growing, locally invasive tumors with low potential for lymphatic metastasis and appear to be radioresistant. We report a case which is unusual in having endometrial and deep myometrial invasion. Electron microscopy, immunohistochemical stains, and DNA in situ hybridization studies failed to detect human papilloma virus particles but the oncogenic potential of the virus is not excluded.

  20. The oncofetal protein IMP3: a novel biomarker for endometrial serous carcinoma.

    PubMed

    Zheng, Wenxin; Yi, Xiaofang; Fadare, Oluwole; Liang, Sharon X; Martel, Maritza; Schwartz, Peter E; Jiang, Zhong

    2008-02-01

    Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein highly expressed in fetal tissue and malignant tumors but rarely found in adult benign tissues. The aim of this study is to determine the expression of IMP3 in benign endometrium, endometrial cancer, and its precursor lesions, trying to see whether IMP3 has any diagnostic usage. Two hundred ninety-eight endometrial samples were examined for IMP3 expression by immunohistochemistry. These included benign endometrium (n=68), atypical hyperplasia or endometrial intraepithelial neoplasia (n=35), endometrial glandular dysplasia (n=21), endometrial intraepithelial carcinoma (n=18), endometrioid carcinoma (n=70), mucinous carcinoma (n=8), serous carcinoma (n=51), clear cell carcinoma (n=12), and other malignancies (n=15). Maturational patterns in the 68 benign endometrial samples included atrophic (n=12), proliferative (n=18), secretory (n=14), menstrual (n=8), and gestational (n=16). Most of the carcinomas were histologically pure; where mixed, the second component constituted <10% of the total tumor volume. The extent and intensity of IMP3 expression was semiquantitatively determined and scored for all samples. A renal cell carcinoma with known IMP3 expression was used as positive control for each immunohistochemistry run. Among the malignant cases, IMP3 expression was predominantly found in endometrial serous carcinoma and its putative precursor lesions, with 3 (14%) of 21 endometrial glandular dysplasia, 16 (89%) of 18 serous endometrial intraepithelial carcinoma, and 48 (94%) of 51 serous carcinomas (P<0.001). In contrast, the frequency of IMP3 expression was significantly lesser in nonserous malignancies with 0 (0%) of 35, 5 (7%) of 70, 0 (0%) of 8, 3 (25%) of 12, and 5 (33%) of 15 positive expression rates in atypical hyperplasia or endometrial intraepithelial neoplasia, endometrioid, mucinous, clear cell carcinomas, and other malignancies, respectively. The IMP3 staining was

  1. 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

  2. Mig-6 modulates uterine steroid hormone responsiveness and exhibits altered expression in endometrial disease.

    PubMed

    Jeong, Jae-Wook; Lee, Hee Sun; Lee, Kevin Y; White, Lisa D; Broaddus, Russell R; Zhang, Yu-Wen; Vande Woude, George F; Giudice, Linda C; Young, Steven L; Lessey, Bruce A; Tsai, Sophia Y; Lydon, John P; DeMayo, Francesco J

    2009-05-26

    Normal endometrial function requires a balance of progesterone (P4) and estrogen (E2) effects. An imbalance caused by increased E2 action and/or decreased P4 action can result in abnormal endometrial proliferation and, ultimately, endometrial adenocarcinoma, the fourth most common cancer in women. We have identified mitogen-inducible gene 6 (Mig-6) as a downstream target of progesterone receptor (PR) and steroid receptor coactivator (SRC-1) action in the uterus. Here, we demonstrate that absence of Mig-6 in mice results in the inability of P4 to inhibit E2-induced uterine weight gain and E2-responsive target genes expression. At 5 months of age, the absence of Mig-6 results in endometrial hyperplasia. Ovariectomized Mig-6(d/d) mice exhibit this hyperplastic phenotype in the presence of E2 and P4 but not without ovarian hormone. Ovariectomized Mig-6(d/d) mice treated with E2 developed invasive endometrioid-type endometrial adenocarcinoma. Importantly, the observation that endometrial carcinomas from women have a significant reduction in MIG-6 expression provides compelling support for an important growth regulatory role for Mig-6 in the uterus of both humans and mice. This demonstrates the Mig-6 is a critical regulator of the response of the endometrium to E2 in regulating tissue homeostasis. Since Mig-6 is regulated by both PR and SRC-1, this identifies a PR, SRC-1, Mig-6 regulatory pathway that is critical in the suppression of endometrial cancer.

  3. A comparison between the effects of metformin and megestrol on simple endometrial hyperplasia.

    PubMed

    Sharifzadeh, Fatemeh; Aminimoghaddam, Soheila; Kashanian, Maryam; Fazaeli, Masoomeh; Sheikhansari, Narges

    2017-02-01

    Endometrial hyperplasia is one of the most serious causes of severe abnormal bleeding and also can be a precursor of endometrial carcinoma. The purpose of the present study was to compare the effects of metformin and megestrol on the endometrial hyperplasia. The study was performed as a randomized clinical trial on 42 cases of histopathologically confirmed simple endometrial hyperplasia without atypia. The eligible women were randomly assigned into two groups. In metformin group, metformin was prescribed, 500 mg twice a day (1000 mg daily), for a duration of 4 weeks, and then, followed by 1500 mg daily, for 8 more weeks. In the megestrol group, megestrol was prescribed 40 mg daily for 12 weeks. At the end of the duration of the treatment, endometrial sampling was performed and the results were compared between the two groups. The women of the two groups did not have significant difference according to age, BMI and gravidity, parity and history of abortion. Overall, 18 women (81.8%) in metformin group and 12 women (60%) in the megestrol group had normal endometrial histology, after 12 weeks of treatment (p = 0.11). Metformin is comparable with megestrol for the treatment of simple endometrial hyperplasia.

  4. Primary sources of pelvic serous cancer in patients with endometrial intraepithelial carcinoma.

    PubMed

    Jia, Lin; Yuan, Zeng; Wang, Yiying; Cragun, Janiel M; Kong, Beihua; Zheng, Wenxin

    2015-01-01

    Serous endometrial intraepithelial carcinoma is often associated with extrauterine disease. It is currently unclear where does the extrauterine disease come from. This study addressed this issue. A total of 135 samples from 21 serous endometrial intraepithelial carcinoma patients were studied. Cellular lineage relationships between intrauterine and extrauterine serous carcinomas were determined by TP53-mutation analysis and correlated to the clinicopathologic features. There were three conditions contributing the extrauterine disease: metastasis from serous endometrial intraepithelial carcinoma (n=10) showed identical TP53 mutation between intrauterine lesions and extrauterine disease, cases of adnexal origin (n=5) had discordant TP53 mutations, and the mixed cellular origin cases (n=6) with both identical and discordant mutation status. Patients with extrauterine disease from serous endometrial intraepithelial carcinoma metastasis typically had small tumor masses (<2 cm) in extrauterine sites and without finding of serous tubal intraepithelial carcinoma, while extrauterine disease with adnexal or tubal origin commonly had larger tumor masses in extrauterine sites including ovary and omentum and serous tubal intraepithelial carcinoma. The majority of extrauterine diseases associated with serous endometrial intraepithelial carcinoma are metastasized from the endometrium. Serous endometrial intraepithelial carcinoma is frequently associated with serous cancers of adnexal or tubal origin, indicating that endometrial and adnexal or tubal serous cancers may share similar etiologies. TP53-mutation analysis provides a strong linkage for cellular lineage analysis. Tumor size in extrauterine disease and presence of serous tubal intraepithelial carcinoma or not are useful clinicopathologic features to determine primary cancer site, which helps in clinical management.

  5. Dietary fat intake and endometrial cancer risk: A dose response meta-analysis.

    PubMed

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

    2016-07-01

    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.

  6. Median Survival Time of Endometrial Cancer Patients with Lymphovascular Invasion at the Hospital Universiti Sains Malaysia.

    PubMed

    Asyikeen, Wan Adnan Wan Nor; Siti-Azrin, Ab Hamid; Jalil, Nur Asyilla Che; Zin, Anani Aila Mat; Othman, Nor Hayati

    2016-11-01

    Endometrial cancer is the most common gynaecologic malignancy among females worldwide. The purpose of this study was to determine the median survival time of endometrial cancer patients at the Hospital Universiti Sains Malaysia (USM). A list of 121 endometrial cancer cases registered at Hospital USM between 2000 until 2011 was retrospectively reviewed. The survival time of the endometrial cancer patients was estimated by Kaplan-Meier survival analysis. Log-rank tests were performed to compare the survival of the patients based on socio-demographics and clinical presentation. Only 108 patients, 87.0%, were included who were of Malay ethnicity. Previous history included menopause in 67.6% of patients and diabetes mellitus in 39.8% of patients; additionally, 63.4% of patients were nulliparous. Tumour staging was as follows: 24.5% stage I, 10.8% stage II, 26.5% stage III and 38.2% stage IV. The overall median survival time of the endometrial cancer patients was 70.20 months (95% confidence interval (CI): 51.79, 88.61). The significant factors were age, the presence of lymphovascular invasion and treatment received. The overall survival of endometrial cancer was low. A prospective study needs to be carried out to discover more effective and accurate tests for the early detection of endometrial cancer.

  7. Factors Influencing the Recurrence Potential of Benign Endometrial Polyps after Hysteroscopic Polypectomy.

    PubMed

    Yang, Jehn-Hsiahn; Chen, Chin-Der; Chen, Shee-Uan; Yang, Yu-Shih; Chen, Mei-Jou

    2015-01-01

    An endometrial polyp is a frequently encountered gynecologic disease with abnormal uterine bleeding and infertility being the two common presenting problems, and hysteroscopic polypectomy is an effective method to remove them. The postoperative polyp recurrence might result in reappearance of abnormal uterine bleeding or infertility, whereas factors influencing the postoperative recurrence potential have limited data. This case-series report included 168 premenopausal women who suffered from endometrial polyps and underwent hysteroscopic polypectomy. All of them were awaiting a future pregnancy. Office hysteroscopy was done before and after hysteroscopic polypectomy, in which preoperative hysteroscopy examined the number, type, and location of endometrial polyps, and postoperative hysteroscopy checked the polyp recurrence. Surgical indications, either infertility or the presentation of abnormal uterine bleeding, and follow-up duration were recorded. Seventy-three out of 168 (43%) women had polyp recurrence after hysteroscopic polypectomy. Multivariate logistic regression analysis revealed that more endometrial polyps (P = 0.015) and longer duration of follow-up (P = 0.004) were significantly associated with an increased risk of postoperative polyp recurrence. The type of endometrial polyps was not correlated with polyp recurrence potential, whereas pedunculated type endometrial polyps were closely related to the presentation of abnormal uterine bleeding (P = 0.001). A higher number of endometrial polyps and longer follow-up duration are associated with a greater potential of polyp recurrence after hysteroscopic polypectomy.

  8. Use of levonorgestrel-releasing intrauterine system in the prevention and treatment of endometrial hyperplasia.

    PubMed

    Ewies, Ayman A A; Alfhaily, Fadi

    2012-11-01

    Endometrial hyperplasia is a commonly seen gynecological condition that affects women of all age groups. Whereas hysterectomy is the most preferred treatment option for complex endometrial hyperplasia with atypia, there is no consensus regarding the first-line management of women with hyperplasia without cytological atypia. Oral progestogen therapy was used with some success. Nonetheless, it may be plausible to argue that women with endometrial hyperplasia need continuous treatment and high level of compliance to ensure complete regression, which may not be guaranteed with oral therapy. Observational studies suggested that levonorgestrel-releasing intrauterine system (LNG-IUS) has been successfully used to treat endometrial hyperplasia without cytological atypia and selected cases of atypical endometrial hyperplasia. Furthermore, there is strong evidence from randomized controlled trials that LNG-IUS prevents the development of endometrial hyperplasia in exogenous estrogen users; however, its protective role and safety in tamoxifen-treated breast cancer survivors remain uncertain. This article evaluates the current evidence for the use of LNG-IUS, releasing 20 μg of LNG per day, in the prevention and treatment of endometrial hyperplasia.

  9. Cyto-histologic evaluation of the endometrium in climacteric women at risk for endometrial carcinoma.

    PubMed

    de Aloysio, D; Rocca, G; Miliffi, L

    1986-08-31

    The authors evaluated the diagnostic effectiveness of a triple specimen technique (cyto-histologic) performed by the Perma device. The incidence of endometrial hyperplasia (according to Dallenbach-Hellweg's classification) was estimated in 254 climacteric women selected from outpatients who come spontaneously to the Menopause Clinic of the Obstetrics and Gynecology Department (Bologna University). The selection criterion was the evidence of risk factors for endometrial carcinoma, climacteric bleedings (obesity, late menopause, high blood pressure, diabetes), or endometriotropic estrogen therapy in the postmenopause. Results showed that the cyto-histologic sampling is most useful for diagnosing endometrial hyperplasia and early carcinoma (diagnostic effectiveness: 89.0-93.8%). Also, endometrial hyperplasia was found to have a significant incidence in the group we examined. This incidence was highest in women with climacteric bleedings, secondly in women using high-dose estrogens, and thirdly in women with risk factors for endometrial carcinoma. When evaluating the different kinds of endometrial hyperplasia, we never found adenomatous hyperplasia in women on estrogen therapy. Affinity between histologic and cytologic classes was around 50% in endometrial hyperplasia and 100% in early carcinoma. This emphasizes that both samplings are needed to perform an accurate diagnosis.

  10. Tubal ligation and risk of endometrial cancer: Findings from the Women’s Health Initiative

    PubMed Central

    Winer, Ira; Lehman, Amy; Wactawski-Wende, Jean; Robinson, Randall; Simon, Michael; Cote, Michele

    2015-01-01

    Objective Bilateral tubal ligation (BTL) is a common form of birth control in the United States. There is limited, contradictory data examining BTL and the risk of endometrial cancer and none examining type I and type II cancers separately. We investigated the association between BTL and endometrial cancer risk utilizing the Women’s Health Initiative (WHI) Observational (OS) and Dietary Modification (DM) Studies. Methods Demographic information and history of BTL were obtained from the baseline questionnaires from 76,483 WHI participants in the OS and DM. Univariable and multivariable models were used to examine the association of BTL with type I and type II endometrial cancers. Results 1,137 women were diagnosed with incident endometrial cancer (972 type I and 128 type II) over a mean follow-up of 11.3 years. Overall, 14,499 women (19%) had undergone BTL. There were no statistically significant associations noted between BTL or age at BTL for type I or type II cancers. Conclusion We examined the largest patient cohort to date in an effort to determine the impact of BTL on endometrial cancer risk. In the WHI trial we observed no overall effect of BTL on the risk of type I or type II endometrial cancer, suggesting that patients undergoing this popular birth-control method likely do not have an associated change in their baseline risk for endometrial cancer. PMID:26825831

  11. Tubal Ligation and Risk of Endometrial Cancer: Findings From the Women's Health Initiative.

    PubMed

    Winer, Ira; Lehman, Amy; Wactawski-Wende, Jean; Robinson, Randal; Simon, Michael; Cote, Michele

    2016-03-01

    Bilateral tubal ligation (BTL) is a common form of birth control in the United States. There are limited, contradictory data examining BTL and the risk of endometrial cancer and none examining type I and type II cancers separately. We investigated the association between BTL and endometrial cancer risk using the Women's Health Initiative (WHI) Observational and Dietary Modification Studies. Demographic information and history of BTL were obtained from the baseline questionnaires from 76,483 WHI participants in the Observational and Dietary Modification Studies. Univariable and multivariable models were used to examine the association of BTL with type I and type II endometrial cancers. A total of 1137 women were diagnosed with incident endometrial cancer (972 type I and 128 type II) during a mean follow-up of 11.3 years. Overall, 14,499 (19%) women had undergone BTL. There were no statistically significant associations noted between BTL and age at BTL for type I or type II cancers. We examined the largest patient cohort to date in an effort to determine the impact of BTL on endometrial cancer risk. In the WHI trial, we observed no overall effect of BTL on the risk of type I or type II endometrial cancer, suggesting that patients undergoing this popular birth control method likely do not have an associated change in their baseline risk for endometrial cancer.

  12. Median Survival Time of Endometrial Cancer Patients with Lymphovascular Invasion at the Hospital Universiti Sains Malaysia

    PubMed Central

    Asyikeen, Wan Adnan Wan Nor; Siti-Azrin, Ab Hamid; Jalil, Nur Asyilla Che; Zin, Anani Aila Mat; Othman, Nor Hayati

    2016-01-01

    Background Endometrial cancer is the most common gynaecologic malignancy among females worldwide. The purpose of this study was to determine the median survival time of endometrial cancer patients at the Hospital Universiti Sains Malaysia (USM). Methods A list of 121 endometrial cancer cases registered at Hospital USM between 2000 until 2011 was retrospectively reviewed. The survival time of the endometrial cancer patients was estimated by Kaplan-Meier survival analysis. Log-rank tests were performed to compare the survival of the patients based on socio-demographics and clinical presentation. Results Only 108 patients, 87.0%, were included who were of Malay ethnicity. Previous history included menopause in 67.6% of patients and diabetes mellitus in 39.8% of patients; additionally, 63.4% of patients were nulliparous. Tumour staging was as follows: 24.5% stage I, 10.8% stage II, 26.5% stage III and 38.2% stage IV. The overall median survival time of the endometrial cancer patients was 70.20 months (95% confidence interval (CI): 51.79, 88.61). The significant factors were age, the presence of lymphovascular invasion and treatment received. Conclusion The overall survival of endometrial cancer was low. A prospective study needs to be carried out to discover more effective and accurate tests for the early detection of endometrial cancer. PMID:28090178

  13. Tumor budding and E-Cadherin expression in endometrial carcinoma: are they prognostic factors in endometrial cancer?

    PubMed

    Koyuncuoglu, Meral; Okyay, Emre; Saatli, Bahadir; Olgan, Safak; Akin, Mustafa; Saygili, Ugur

    2012-04-01

    To evaluate the prognostic value of tumor budding (TB) in endometrioid (EEC) and non-endometrioid endometrial cancers (NEEC) and to determine its correlation with expression of E-cadherin. Ninety-five patients with primary endometrial carcinoma were examined statistically. All patients were diagnosed, treated, and given follow-up care at Dokuz Eylul University Faculty of Medicine. Tumor budding detected by either H&E-stained sections and anticytokeratin-staining C11. The tissue block with the largest invasive front was chosen for budding counting and immunostaining. E-cadherin expression was examined by immunohistochemistry using the primary antibodies against to it. Tumor budding was low-grade in 73 and high-grade in 22 cases. E-cadherin expression loss was identified in 48 patients. The high-grade TB was significantly higher in patients with advanced stage and deep myometrial invasion (p=0.032 and 0.018, respectively). E-Cadherin expression was significantly lower in NEECs than EECs (p=0.032). The negative expression of E-cadherin was associated with advanced stage and poor differentiation (p=0.001 and p=0.024, respectively). We determined that tumor budding adversely correlated with the presence of E-cadherin expression but not statistically significant. Based on the results of multivariate analysis, TB has an independent impact on cumulative overall survival. We found no statistically significant difference between E-cadherin expression and survival. TB is associated with undifferentiated tumor, advanced stage and decreased postoperative survival in endometrial cancer. It might be a valuable prognostic clinicopathologic factor which can be applicable in routine examination. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Expression of MIF and c-erbB-2 in endometrial cancer.

    PubMed

    Xiao, Wei; Dong, Xiujuan; Zhao, Honghui; Han, Shiyu; Nie, Ruixue; Zhang, Xiahua; An, Ruifang

    2016-05-01

    The aim of the present study was to investigate the expression of c-erbB-2 and macrophage migration inhibitory factor (MIF) in endometrial cancer and to elucidate the significance of the early diagnosis and prognosis of endometrial cancer. The gene copy number of c‑erbB‑2 and MIF was characterized by reverse transcription quantitative polymerase chain reaction and the reactivity was assessed by immunohistochemistry in 70 patients using a polyclonal antibody, and evaluated semiquantitatively according to the percentage of cells demonstrating membranous or diffuse cytoplasmic staining. A correlation between age, tumor stage, grade, myometrial invasion and lymph node metastasis was observed. The mRNA expression of c‑erbB‑2 and MIF was high in endometrial carcinoma. The positive expression rate of MIF protein in normal endometrium, atypical hyperplasia and endometrial carcinoma significantly increased along with the degree of aggravation of the disease by 20 (3/15), 45 (9/20) and 70% (35/50), respectively. The positive expression of MIF and c‑erbB‑2 was highest in endometrial cancer and a significantly higher level of protein was observed in tumors at stage I, stage G1, with a depth of myometrial invasion <0.4 cm and no lymph node metastasis. The protein expression of c‑erbB‑2 in endometrial cancer was higher in tumors at the G2‑3 phase, clinical stage III‑IV, lymph node metastasis, and had no association with the depth of myometrial invasion and age. MIF and c‑erbB‑2 were correlated with the occurrence and the development of endometrial cancer, and thus can be used for the early diagnosis and prognosis of endometrial cancer. The present study laid the foundation for identifying new treatments for endometrial cancer.

  15. Analysis of methylation profiling data of hyperplasia and primary and metastatic endometrial cancers.

    PubMed

    Wu, Xihai; Miao, Jilan; Jiang, Jingyan; Liu, Fangmei

    2017-10-01

    Endometrial cancer is a prevalent cancer, and its metastasis causes low survival rate. This study aims to utilize DNA methylation data to investigate the mechanism of the development and metastasis of endometrial cancer. Methylation profiling data were down-loaded from Gene Expression Omnibus, including 8 hyperplasias, 33 primary and 53 metastatic endometrial cancers. COHCAP package and annotation files were utilized to identify differentially methylated genes (DMGs) and CpG islands between the three different endometrial diseases. STRING database and Cytoscape were used to analyze and visualize protein-protein interactions (PPIs) between DMGs. CytoNCA plugin was utilized to identify key nodes in PPI network. A total of 610, 1076, and 501 DMGs were identified between primary endometrial cancer and hyperplasia, metastatic endometrial cancer and hyperplasia, as well as metastatic and primary endometrial cancers, respectively. For the three DMG sets, 53 common hypermethylated DMGs (e.g. PAX6 and INSR) and 6 common hypomethylated DMGs (e.g. PRDM8, KLHL14, and DUSP6) were found. For primary-hyperplasia DMG set and metastasis-hyperplasia DMG set, 527 common DMGs were found. For these common DMGs, a PPI network involving 692 PPIs was constructed. For DMGs between metastatic and primary endometrial cancers, a PPI network involving 673 PPIs was established, with PAX6 and INSR in the top 20 DMGs in both networks. PRDM8, KLHL14, and DUSP6 had hypomethylated CpG islands. DMGs comparison, PPI network analysis, and analysis of differentially methylated CpG islands indicated that PAX6, INSR, PRDM8, KLHL14, and DUSP6 might participate in the development and metastasis of endometrial cancer. Copyright © 2017. Published by Elsevier B.V.

  16. Dietary acrylamide intake and risk of endometrial cancer in prospective cohort studies.

    PubMed

    Je, Youjin

    2015-06-01

    Acrylamide has been associated with carcinogenicity in experimental animals, but potential health risks of dietary acrylamide intake and endometrial cancer in human are inconclusive. Thus, a meta-analysis of prospective cohort studies was conducted to provide a quantitative assessment of the association between dietary acrylamide intake and endometrial cancer risk. PubMed database was used to identify prospective cohort studies on dietary acrylamide intake and endometrial cancer risk published up to June 2014. Since smoking is an important source of acrylamide and is inversely associated with endometrial cancer risk, the association was examined in women who never smoked as well. Multivariable relative risks (RR) adjusting for potential confounders were combined using random effects models. Four large prospective cohort studies were identified, which included 453,355 female participants and 2,019 endometrial cancer cases. There was no association between dietary acrylamide intake and endometrial cancer risk overall [pooled RR for high vs. low intake = 1.10; 95% confidence interval (CI) 0.91-1.34]. High acrylamide intake, however, was significantly associated with increased risk of endometrial cancer among women who never smoked (pooled RR for high vs. low intake = 1.39; 95% CI 1.09-1.77). In dose-response analyses, pooled RRs for an increase of 10 µg/day were 1.04 (95% CI 0.97-1.11) among all women and 1.11 (95% CI 1.04-1.19) among never-smoking women. Endometrial cancer risk was not associated with dietary acrylamide intake overall. Among women who never smoked, however, there was a significantly increased endometrial cancer risk in women who consumed high dietary acrylamide.

  17. Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis

    PubMed Central

    Nead, Kevin T.; Sharp, Stephen J.; Thompson, Deborah J.; Painter, Jodie N.; Savage, David B.; Semple, Robert K.; Barker, Adam; Perry, John R. B.; Attia, John; Dunning, Alison M.; Easton, Douglas F.; Holliday, Elizabeth; Lotta, Luca A.; O’Mara, Tracy; McEvoy, Mark; Pharoah, Paul D. P.; Scott, Rodney J.; Spurdle, Amanda B.; Langenberg, Claudia; Wareham, Nicholas J.

    2015-01-01

    Background: Insulinemia and type 2 diabetes (T2D) have been associated with endometrial cancer risk in numerous observational studies. However, the causality of these associations is uncertain. Here we use a Mendelian randomization (MR) approach to assess whether insulinemia and T2D are causally associated with endometrial cancer. Methods: We used single nucleotide polymorphisms (SNPs) associated with T2D (49 variants), fasting glucose (36 variants), fasting insulin (18 variants), early insulin secretion (17 variants), and body mass index (BMI) (32 variants) as instrumental variables in MR analyses. We calculated MR estimates for each risk factor with endometrial cancer using an inverse-variance weighted method with SNP-endometrial cancer associations from 1287 case patients and 8273 control participants. Results: Genetically predicted higher fasting insulin levels were associated with greater risk of endometrial cancer (odds ratio [OR] per standard deviation = 2.34, 95% confidence internal [CI] = 1.06 to 5.14, P = .03). Consistently, genetically predicted higher 30-minute postchallenge insulin levels were also associated with endometrial cancer risk (OR = 1.40, 95% CI = 1.12 to 1.76, P = .003). We observed no associations between genetic risk of type 2 diabetes (OR = 0.91, 95% CI = 0.79 to 1.04, P = .16) or higher fasting glucose (OR = 1.00, 95% CI = 0.67 to 1.50, P = .99) and endometrial cancer. In contrast, endometrial cancer risk was higher in individuals with genetically predicted higher BMI (OR = 3.86, 95% CI = 2.24 to 6.64, P = 1.2x10-6). Conclusion: This study provides evidence to support a causal association of higher insulin levels, independently of BMI, with endometrial cancer risk. PMID:26134033

  18. Evidence of a Causal Association Between Insulinemia and Endometrial Cancer: A Mendelian Randomization Analysis.

    PubMed

    Nead, Kevin T; Sharp, Stephen J; Thompson, Deborah J; Painter, Jodie N; Savage, David B; Semple, Robert K; Barker, Adam; Perry, John R B; Attia, John; Dunning, Alison M; Easton, Douglas F; Holliday, Elizabeth; Lotta, Luca A; O'Mara, Tracy; McEvoy, Mark; Pharoah, Paul D P; Scott, Rodney J; Spurdle, Amanda B; Langenberg, Claudia; Wareham, Nicholas J; Scott, Robert A

    2015-09-01

    Insulinemia and type 2 diabetes (T2D) have been associated with endometrial cancer risk in numerous observational studies. However, the causality of these associations is uncertain. Here we use a Mendelian randomization (MR) approach to assess whether insulinemia and T2D are causally associated with endometrial cancer. We used single nucleotide polymorphisms (SNPs) associated with T2D (49 variants), fasting glucose (36 variants), fasting insulin (18 variants), early insulin secretion (17 variants), and body mass index (BMI) (32 variants) as instrumental variables in MR analyses. We calculated MR estimates for each risk factor with endometrial cancer using an inverse-variance weighted method with SNP-endometrial cancer associations from 1287 case patients and 8273 control participants. Genetically predicted higher fasting insulin levels were associated with greater risk of endometrial cancer (odds ratio [OR] per standard deviation = 2.34, 95% confidence internal [CI] = 1.06 to 5.14, P = .03). Consistently, genetically predicted higher 30-minute postchallenge insulin levels were also associated with endometrial cancer risk (OR = 1.40, 95% CI = 1.12 to 1.76, P = .003). We observed no associations between genetic risk of type 2 diabetes (OR = 0.91, 95% CI = 0.79 to 1.04, P = .16) or higher fasting glucose (OR = 1.00, 95% CI = 0.67 to 1.50, P = .99) and endometrial cancer. In contrast, endometrial cancer risk was higher in individuals with genetically predicted higher BMI (OR = 3.86, 95% CI = 2.24 to 6.64, P = 1.2x10(-6)). This study provides evidence to support a causal association of higher insulin levels, independently of BMI, with endometrial cancer risk. © The Author 2015. Published by Oxford University Press.

  19. Estrogen receptor α wields treatment-specific enhancers between morphologically similar endometrial tumors

    PubMed Central

    Droog, Marjolein; Nevedomskaya, Ekaterina; Dackus, Gwen M.; Fles, Renske; Kim, Yongsoo; Hollema, Harry; Mourits, Marian; Nederlof, Petra M.; van Boven, Hester H.; Linn, Sabine C.; van Leeuwen, Flora E.; Wessels, Lodewyk F. A.; Zwart, Wilbert

    2017-01-01

    The DNA-binding sites of estrogen receptor α (ERα) show great plasticity under the control of hormones and endocrine therapy. Tamoxifen is a widely applied therapy in breast cancer that affects ERα interactions with coregulators and shifts the DNA-binding signature of ERα upon prolonged exposure in breast cancer. Although tamoxifen inhibits the progression of breast cancer, it increases the risk of endometrial cancer in postmenopausal women. We therefore asked whether the DNA-binding signature of ERα differs between endometrial tumors that arise in the presence or absence of tamoxifen, indicating divergent enhancer activity for tumors that develop in different endocrine milieus. Using ChIP sequencing (ChIP-seq), we compared the ERα profiles of 10 endometrial tumors from tamoxifen users with those of six endometrial tumors from nonusers and integrated these results with the transcriptomic data of 47 endometrial tumors from tamoxifen users and 64 endometrial tumors from nonusers. The ERα-binding sites in tamoxifen-associated endometrial tumors differed from those in the tumors from nonusers and had distinct underlying DNA sequences and divergent enhancer activity as marked by histone 3 containing the acetylated lysine 27 (H3K27ac). Because tamoxifen acts as an agonist in the postmenopausal endometrium, similar to estrogen in the breast, we compared ERα sites in tamoxifen-associated endometrial cancers with publicly available ERα ChIP-seq data in breast tumors and found a striking resemblance in the ERα patterns of the two tissue types. Our study highlights the divergence between endometrial tumors that arise in different hormonal conditions and shows that ERα enhancer use in human cancer differs in the presence of nonphysiological endocrine stimuli. PMID:28167798

  20. Perineal powder use and risk of endometrial cancer in postmenopausal women.

    PubMed

    Crawford, Lori; Reeves, Katherine W; Luisi, Nicole; Balasubramanian, Raji; Sturgeon, Susan R

    2012-10-01

    Most known endometrial cancer risk factors involve genetics or exposure to unopposed estrogens; less is known about risk due to environmental exposures. While several studies have found an increased risk of ovarian cancer associated with perineal powder use, only two studies have addressed perineal powder use and endometrial cancer risk. We used Cox proportional hazards regression to examine the association between perineal powder use and endometrial cancer risk using the Women's Health Initiative Observational Study Research Materials obtained from the National Heart, Lung, and Blood Institute Biological Specimen and Data Repository Coordinating Center. Of the 48,526 women in our primary analysis, 25,181 (52 %) reported ever use of perineal powder. During 364,134 person-years of follow-up, 447 participants were diagnosed with endometrial cancer. Ever use of perineal powder was not associated with increased risk of endometrial cancer (multivariable-adjusted hazard ratio, 1.06; 95 % confidence interval, 0.87-1.28). External use of powder on the genitals and/or on sanitary napkins was also not significantly associated with risk of endometrial cancer. However, use of powder on a diaphragm for twenty or more years was associated with a threefold increase in risk of endometrial cancer compared to women who never used perineal powder (multivariable-adjusted hazard ratio, 3.06; 95 % CI, 2.00-4.70). Any duration of external use of perineal powder was not associated with increased risk of endometrial cancer; however, long-term use of powder on a diaphragm may increase the risk of endometrial cancer.

  1. Endometrial cytopathology. An image analysis approach using the Ki-67 biomarker.

    PubMed

    Apostolou, G; Apostolou, N; Moulos, P; Chatzipantelis, P

    2017-10-01

    To investigate the different identity and biological behaviour of endometrial benign epithelial and endometrial adenocarcinoma cell categories. For this study, the imprint smears from three groups, 10 cases of disordered proliferative/benign hyperplastic endometrium, 21 cases of low-grade and eight cases of high-grade endometrial adenocarcinoma, were examined using image analysis and the Ki-67 biomarker. The plastic stem cell model was also applied. Among the examined groups, the nuclear area major axis ranged statistically different in the digitally measured Ki-67 positive endometrial epithelial and adenocarcinoma cells (P<.0001). Moreover, higher values of the cycling nuclear area major axis were observed in high-grade, as compared with the low-grade endometrial adenocarcinomas (P<.0001) and the cases of disordered/benign hyperplastic endometrium (P<.0001). Additionally, a Ki-67 increase pathway was observed in the benign endometrial lesions, and a relatively stable pathway was noticed in low- and high-grade endometrial adenocarcinomas. The different range of the nuclear area major axis among cycling endometrial epithelial and adenocarcinoma cells may correlate with their specific identity and biological behaviour. The different values of the cycling nuclear area major dimension may also be connected with the biological behaviour of the three examined groups. Moreover, the endometrial epithelial cells may follow a Ki-67 increase pathway, instead of the relatively stable pathway which the rapidly proliferating adenocarcinoma cells may use. Finally, the studied cell categories may exhibit different biology, because their stem cells may reside in different states of stemness. © 2017 John Wiley & Sons Ltd.

  2. ATM may be a protective factor in endometrial carcinogenesis with the progesterone pathway.

    PubMed

    Shan, Weiwei; Wang, Chao; Zhang, Zhenbo; Luo, Xuezhen; Ning, Chengcheng; Yu, Yinhua; Feng, Youji; Gu, Chao; Chen, Xiaojun

    2015-03-01

    The purpose of the study was to explore the role and mechanism of ataxia-telangiectasia mutated (ATM) protein in endometrial carcinogenesis. A reverse-phase protein array (RPPA) was used to analyze the expression of ATM signal pathway proteins in Ishikawa and progesterone-insensitive Ishikawa. ATM expression was detected in endometrium specimens by immunohistochemistry, including 8 cases with proliferative endometrium, 6 cases with secretory endometrium, 10 cases with simple hyperplasia (SH), 13 cases of complex hyperplasia (CH), 11 cases of endometrial atypical hyperplasia (EAH), and 83 cases with type I endometrial cancer. The relationship between ATM expression and other clinicopathological indicators was also examined in type I endometrial cancer patients. The mechanisms of ATM were explored in vitro with the endometrial cell lines Ishikawa and RL95-2. A cell counting kit-8 (CCK-8) test and Western blot analysis were performed to test proliferation and protein expression. Statistical analysis was performed with SPSS19.0. The significance level was set at 0.05. ATM was increased with medroxyprogesterone acetate (MPA) stimulation in Ishikawa in RPPA. ATM expression gradually decreased in endometrial hyperplasic lesions compared with the normal proliferative and secretory endometrium and was the lowest in type I endometrial cancer. ATM expression was negatively correlated with pathological grades in type I endometrial cancer. In vitro, ATM silencing retarded proliferation inhibition in Ishikawa and RL95-2 treated with MPA. ATM silencing could down-regulate the MPA-stimulated signal proteins, including Chk2, P53, and caspase-3 in vitro. MPA might exert its role through activating the ATM-associated pathway, ATM-Chk2-P53-caspase-3 (active), preserving normal endometrium and protecting it from malignancies. ATM might be a promising indicator for endometrial hyperplasia and cancer.

  3. RNASeq analysis reveals biological processes governing the clinical behaviour of endometrioid and serous endometrial cancers.

    PubMed

    Lemetre, Christophe; Vieites, Begoña; Ng, Charlotte K Y; Piscuoglio, Salvatore; Schultheis, Anne M; Marchiò, Caterina; Murali, Rajmohan; Lopez-García, Maria A; Palacios, Jose C; Jungbluth, Achim A; Terracciano, Luigi M; Reis-Filho, Jorge S; Weigelt, Britta

    2016-09-01

    Endometrial carcinoma comprises a group of tumours with distinct histologic and molecular features and clinical behaviour. Here, we sought to define the biological processes that govern the clinical behaviour of endometrial cancers. Sixteen prototype genes representative of different biological processes that would likely play a role in endometrial and other hormone-driven cancers were defined. RNA-sequencing gene expression data from 323 endometrial cancers from The Cancer Genome Atlas (TCGA) were used to determine the transcription module of each prototype gene. The expression of prototype genes and modules and their association with outcome was assessed in univariate and multivariate survival analyses. The association of MSH6 expression with outcome was validated in an independent cohort of 243 primary endometrial cancers using immunohistochemistry. We observed that the clinical behaviour of endometrial cancers as a group was associated with hormone receptor signalling, PI3K pathway signalling and DNA mismatch repair processes. When analysed separately, in endometrioid carcinomas, hormone receptor, PI3K and DNA mismatch repair modules were significantly associated with outcome in univariate analysis, whereas the clinical behaviour of serous cancers was likely governed by apoptosis and Wnt signalling. Multivariate survival analysis revealed that MSH6 gene expression was associated with outcome of endometrial cancer patients independently from traditional prognostic clinicopathologic parameters, which was confirmed in an independent cohort at the protein level. Endometrioid and serous endometrial cancers are underpinned by distinct molecular pathways. MSH6 expression levels may be associated with outcome in endometrial cancers as a group. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Presence of HHV-6A in Endometrial Epithelial Cells from Women with Primary Unexplained Infertility

    PubMed Central

    Bortolotti, Daria; Lo Monte, Giuseppe; Caselli, Elisabetta; Bolzani, Silvia; Rotola, Antonella; Di Luca, Dario; Rizzo, Roberta

    2016-01-01

    To elucidate the roles of human herpesvirus (HHV)-6 primary unexplained infertile women, a prospective randomized study was conducted on a cohort of primary unexplained infertile women and a cohort of control women, with at least one successful pregnancy. HHV-6 DNA was analyzed and the percentage and immune-phenotype of resident endometrial Natural Killer (NK) cells, as the first line of defense towards viral infections, was evaluated in endometrial biopsies. Cytokine levels in uterine flushing samples were analyzed. HHV-6A DNA was found in 43% of endometrial biopsies from primary unexplained infertile women, but not in control women. On the contrary, HHV-6B DNA was absent in endometrial biopsies, but present in PBMCs of both cohorts. Endometrial NK cells presented a different distribution in infertile women with HHV6-A infection compared with infertile women without HHV6-A infection. Notably, we observed a lower percentage of endometrial specific CD56brightCD16- NK cells. We observed an enhanced HHV-6A-specific endometrial NK cell response in HHV-6A positive infertile women, with a marked increase in the number of endometrial NK cells activating towards HHV-6A infected cells. The analysis of uterine flushing samples showed an increase in IL-10 levels and a decrease of IFN-gamma concentrations in infertile women with HHV6-A infection. Our study indicates, for the first time, that HHV-6A infection might be an important factor in female unexplained infertility development, with a possible role in modifying endometrial NK cells immune profile and ability to sustain a successful pregnancy. PMID:27367597

  5. Biomarkers of progestin therapy resistance and endometrial hyperplasia progression

    PubMed Central

    Upson, Kristen; Allison, Kimberly H.; Reed, Susan D.; Jordan, Carolyn D.; Newton, Katherine M.; Swisher, Elizabeth M.; Doherty, Jennifer A.; Garcia, Rochelle L.

    2012-01-01

    Objective To identify biomarkers associated with progestin therapy resistance and persistence/progression of endometrial hyperplasia. Study Design We performed a nested case-control study among women with complex (n=73) and atypical (n=41) hyperplasia treated with oral progestin, followed 2–6 months for persistence/progression. We evaluated index endometrial protein expression for progesterone receptors A (PRA) and B (PRB), PTEN, Pax-2 and Bcl-2. Odds ratios and 95% confidence intervals were estimated. Results Among women with atypical hyperplasia, high PRB expression was associated with 90% decreased risk of persistence/progression (95% CI: 0.01–0.8). High expression of PRA and PRB suggested decreased risk of persistence/ progression (OR=0.1, 95% CI: 0.02–1.0). These findings were not observed among women with complex hyperplasia. No associations were found with PTEN, Pax-2, and Bcl-2 protein expression. Conclusions PRB expression shows promise as a biomarker of progestin response. Further research is warranted to understand how PRB expression may guide treatment decisions. PMID:22727345

  6. Unexpected locations of sentinel lymph nodes in endometrial cancer.

    PubMed

    How, Jeffrey; Boldeanu, Irina; Lau, Susie; Salvador, Shannon; How, Emily; Gotlieb, Raphael; Abitbol, Jeremie; Halder, Ajay; Amajoud, Zainab; Probst, Stephan; Brin, Sonya; Gotlieb, Walter

    2017-10-01

    To evaluate the anatomical location of sentinel lymph nodes (SLN) following intra-operative cervical injection in endometrial cancer. All consecutive patients with endometrial cancer undergoing sentinel lymph node mapping were included in this prospective study following intra-operative cervical injection of tracers. Areas of SLN detection distribution were mapped. Among 436 patients undergoing SLN mapping, there were 1095 SLNs removed, and 7.9% of these SLNs found in 13.1% of patients, were detected in areas not routinely harvested during a standard lymph node dissection. These included the internal iliac vein, parametrial, and pre-sacral areas. The SLN was the only positive node in 46.1% (15/36) of cases with successful mapping and completion lymphadenectomy, including 3 cases where the sentinel node in the atypical location was the only node with metastatic disease. SLN mapping using intra-operative cervical injection is capable to map out areas not typically included in a standard lymphadenectomy. The sentinel node is the most relevant lymph node to analyze and may enable to discover metastatic disease in unusual areas. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Endometrial ablation using SideFire laser fiber

    NASA Astrophysics Data System (ADS)

    Everett, Royice B.

    1996-05-01

    The first successful report using the neodymium:yttrium-aluminum-garnet (Nd:YAG) Laser to control hypermenorrhea was reported in 1981. Variations on the treatment technique have been attempted to improve the amenorrhea rate. Reports using the Nd:YAG laser with the blanching or non-touch technique seem to result in a better outcome and higher rate of total amenorrhea than using the dragging technique. Due to the report of improved rates of amenorrhea when using the blanching technique and the Nd:YAG laser, a fiber was developed to direct the laser energy at right angles to the axis of the fiber, therefore allowing a total treatment of the entire uterus in a perpendicular fashion. The theoretic benefit of this would be a more complete and predictable destruction of the endometrial lining, avoiding fluid overload by coagulating and sealing of the vessels and lymphatic. After a follow-up of 12 to 36 months, 56 of the 60 patients (93%) who underwent complete endometrial ablation with the SideFireTM technique had excellent results. Total absolute amenorrhea resulted in 50 patients (83%). Contrary to earlier reports, using the rollerball electrode, this procedure technique resulted in no decrease in results in younger patients. In conclusion, this seems to be a reasonable alternative which offers improved results when compared to previously available methods using electrosurgery or the Nd:YAG laser without the use of the SideFireTM device.

  8. Targeted endometrial cancer therapy as a future prospect.

    PubMed

    Thanapprapasr, Duangmani; Cheewakriangkrai, Chalong; Likittanasombut, Puchong; Thanapprapasr, Kamolrat; Mutch, David G

    2013-03-01

    Among female-specific cancers worldwide, endometrial cancer is the third most common after breast cancer and cervical cancer. In addition, it is the most common gynecological cancer in the USA and Europe. The incidence of this disease appears to be increasing. The cause of this increase is multifactorial, but a few possible factors involved are increasing obesity, an aging population leading to more postmenopausal women and greater tamoxifen use. Surgery is generally the primary treatment of this disease and postoperative radiation therapy in some patients with high or intermediate risk may prevent locoregional recurrences. Adjuvant chemotherapy improves progression-free survival in advanced or recurrent cancer. However, overall survival in patients with advanced disease is poor. Hence, better therapy is needed and targeted molecular therapies are emerging as possible treatment candidates. These include molecules that target VEGF, mTOR, tyrosine kinases, human EGF receptors and FGF receptors. Therapies targeting specific molecular features should be evaluated in future strategies in the treatment of endometrial cancer.

  9. Expression of epigenetic effectors in decidualizing human endometrial stromal cells.

    PubMed

    Grimaldi, Giulia; Christian, Mark; Quenby, Siobhan; Brosens, Jan J

    2012-09-01

    Cyclic differentiation of human endometrial stromal cells (HESCs) into decidual cells is a highly coordinated process essential for embryo implantation and pregnancy. This differentiation process is closely recapitulated in culture upon exposure of purified HESCs to cyclic AMP and progesterone signaling. Mining of gene expression data revealed that HESCs express 147 genes coding for epigenetic effectors, 33 (22%) of which are significantly regulated (P < 0.05) upon decidualization. Among these are genes encoding for histone-modifying proteins and their cofactors, histone-binding proteins, histone variants, CpG-binding proteins and DNA methyltransferases (DNMTs). Interestingly, more than two-thirds of differentially expressed chromatin-modifying genes are down-regulated upon the transition from a proliferative to a differentiated HESC phenotype. Despite the strong regulation of DNMTs, colorimetric and long interspersed nuclear element 1 methylation assays did not show global changes in DNA methylation levels upon differentiation of HESCs. Taken together, the coordinated regulation of diverse effector molecules suggests that complex epigenetic modification at specific loci underpins the acquisition of a decidual endometrial phenotype.

  10. STAT1 drives tumor progression in serous papillary endometrial cancer.

    PubMed

    Kharma, Budiman; Baba, Tsukasa; Matsumura, Noriomi; Kang, Hyun Sook; Hamanishi, Junzo; Murakami, Ryusuke; McConechy, Melissa M; Leung, Samuel; Yamaguchi, Ken; Hosoe, Yuko; Yoshioka, Yumiko; Murphy, Susan K; Mandai, Masaki; Hunstman, David G; Konishi, Ikuo

    2014-11-15

    Recent studies of the interferon-induced transcription factor STAT1 have associated its dysregulation with poor prognosis in some cancers, but its mechanistic contributions are not well defined. In this study, we report that the STAT1 pathway is constitutively upregulated in type II endometrial cancers. STAT1 pathway alteration was especially prominent in serous papillary endometrial cancers (SPEC) that are refractive to therapy. Our results defined a "SPEC signature" as a molecular definition of its malignant features and poor prognosis. Specifically, we found that STAT1 regulated MYC as well as ICAM1, PD-L1, and SMAD7, as well as the capacity for proliferation, adhesion, migration, invasion, and in vivo tumorigenecity in cells with a high SPEC signature. Together, our results define STAT1 as a driver oncogene in SPEC that modulates disease progression. We propose that STAT1 functions as a prosurvival gene in SPEC, in a manner important to tumor progression, and that STAT1 may be a novel target for molecular therapy in this disease.

  11. Aberrant promoter hypermethylation of p16 gene in endometrial carcinoma.

    PubMed

    Hu, Zhuo-ying; Tang, Liang-dan; Zhou, Qin; Xiao, Lin; Cao, Yi

    2015-03-01

    Previous studies demonstrated that the loss of function of the p16INK4A gene is mainly caused by the hypermethylation of p16 gene promoter; however, whether or not it is associated with the incidence of endometrial carcinoma (EC) remains unclear. In the current study, we conducted a meta-analysis to investigate the effects of p16 gene promoter hypermethylation on the incidence of EC. Detailed research publications were searched from Embase, PubMed, and ISI Web of Knowledge for composition in English or Chinese. The pooled data were collected and analyzed by Review Manager 5.2. Odds ratios (ORs) were calculated and summarized respectively. Six eligible studies, including 261 patients were selected and analyzed. The pooled OR was 0.42, test for overall effect, Z = 10.19, P < 0.0001, indicating that p16 gene promoter hypermethylation was significantly correlated with the EC patients. The results of our study strongly suggest that p16 gene promoter hypermethylation is correlated with an increased risk of EC. P16 gene promoter hypermethylation plays a critical role in endometrial carcinogenesis.

  12. Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding.

    PubMed

    Fergusson, Rosalie J; Lethaby, Anne; Shepperd, Sasha; Farquhar, Cindy

    2013-11-29

    Heavy menstrual bleeding (HMB), which includes both menorrhagia and metrorrhagia, is an important cause of ill health in women. Surgical treatment of HMB often follows failed or ineffective medical therapy. The definitive treatment is hysterectomy, but this is a major surgical procedure with significant physical and emotional complications, as well as social and economic costs. Several less invasive surgical techniques (e.g. transcervical resection of the endometrium (TCRE), laser approaches) and various methods of endometrial ablation have been developed with the purpose of improving menstrual symptoms by removing or ablating the entire thickness of the endometrium. The objective of this review is to compare the effectiveness, acceptability and safety of techniques of endometrial destruction by any means versus hysterectomy by any means for the treatment of heavy menstrual bleeding. Electronic searches for relevant randomised controlled trials (RCTs) targeted but were not limited to the following: the Cochrane Menstrual Disorders and Subfertility Group Register of Trials, MEDLINE, EMBASE, PsycINFO and the Cochrane CENTRAL register of trials. Attempts were made to identify trials by examining citation lists of review articles and guidelines and by performing handsearching. Searches were performed in 2007, 2008 and 2013. Included in the review were any RCTs that compared techniques of endometrial destruction by any means with hysterectomy by any means for the treatment of heavy menstrual bleeding in premenopausal women. Two review authors independently searched for studies, extracted data and assessed risk of bias. Risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes were estimated from the data. Outcomes analysed included improvement in menstrual blood loss, satisfaction, change in quality of life, duration of surgery and hospital stay, time to return to work, adverse events and requirements for repeat surgery due to failure

  13. Endometrial cancer. Prevention, detection, management, and follow up.

    PubMed Central

    Elit, L.

    2000-01-01

    OBJECTIVE: To review risk factors for uterine cancer; to discuss strategies for detecting uterine cancer; to outline prognostic factors and treatment; and to review the role of follow up for patients who have completed primary therapy. QUALITY OF EVIDENCE: MEDLINE was searched from January 1996 to June 1998 using the terms endometrial neoplasms, estrogen replacement therapy, hormone replacement therapy, tamoxifen, and screening. Only English language articles were reviewed. Study types included reviews. Bibliographies of articles found were searched for further relevant titles. Causation literature is available from well conducted cohort trials. Treatment recommendations are based in part on prognostic information and a few randomized controlled trials. MAIN MESSAGE: Risk factors, both intrinsic and extrinsic, are associated with uterine cancer. Family physicians have a role in preventing disease by ensuring that all women with uteri in situ using hormone replacement therapy (HRT) have progesterone therapy as part of the HRT regimen. Detection is crucial; abnormal uterine bleeding or undiagnosed postmenopausal bleeding warrants investigation with endometrial biopsy. The goal of surgery is to remove the uterus and ovaries and identify factors that make the disease at high risk of recurrence. Although adjuvant radiation therapy does not prolong survival, it does alter the pattern of disease recurrence. The goal of follow up after primary therapy is to identify recurrent disease while it is still curable. CONCLUSIONS: Family physicians play an important role in preventing uterine cancer, initiating early diagnosis of disease, and in the future, might be more actively involved in caring for patients following primary therapy. PMID:10790821

  14. Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study.

    PubMed

    Castrillon, Diego H; Lee, Kenneth R; Nucci, Marisa R

    2002-01-01

    We investigated the possibility of distinguishing between primary endometrial and endocervical adenocarcinomas by using a panel of immunohistochemical stains, which included vimentin (VIM), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratins 7 and 20 (CK7 and CK20). Twenty-nine endocervical adenocarcinomas (CCAs) and 30 endometrial adenocarcinomas (EMCAs) including cases with overlapping histologic features (CCAs with endometrioid differentiation [15/29] and EMCAs with mucinous differentiation [16/30]) were evaluated. Most EMCAs (29/30, 97%) were VIM positive, whereas only 2/29 (7%) CCAs were VIM positive. The great majority of EMCAs (28/30) and all 29 CCAs were CK7 positive, whereas all 30 EMCAs and 27/29 CCAs were negative for CK20. CEA positivity was more common in CCAs (18/29, 62%) than in EMCAs (8/30, 27%). EMA positivity was present in all 30 EMCAs and in 26 of 29 (90%) CCAs. We conclude that VIM and CEA are useful immunohistochemical markers in distinguishing EMCAs and CCAs, but CK7, CK20, and EMA are not useful in this distinction.

  15. Antioxidants block proteasome inhibitor function in endometrial carcinoma cells.

    PubMed

    Llobet, David; Eritja, Nuria; Encinas, Mario; Sorolla, Anabel; Yeramian, Andree; Schoenenberger, Joan Antoni; Llombart-Cussac, Antonio; Marti, Rosa M; Matias-Guiu, Xavier; Dolcet, Xavier

    2008-02-01

    We have recently demonstrated that proteasome inhibitors can be effective in inducing apoptotic cell death in endometrial carcinoma cell lines and primary culture explants. Increasing evidence suggests that reactive oxygen species are responsible for proteasome inhibitor-induced cell killing. Antioxidants can thus block apoptosis (cell death) triggered by proteasome inhibition. Here, we have evaluated the effects of different antioxidants (edaravone and tiron) on endometrial carcinoma cells treated with aldehyde proteasome inhibitors (MG-132 or ALLN), the boronic acid-based proteasome inhibitor (bortezomib) and the epoxyketone, epoxomicin. We show that tiron specifically inhibited the cytotoxic effects of bortezomib, whereas edaravone inhibited cell death caused by aldehyde-based proteasome inhibitors. We have, however, found that edaravone completely inhibited accumulation of ubiquitin and proteasome activity decrease caused by MG-132 or ALLN, but not by bortezomib. Conversely, tiron inhibited the ubiquitin accumulation and proteasome activity decrease caused by bortezomib. These results suggest that edaravone and tiron rescue cells of proteasome inhibitors from cell death, by inhibiting blockade of proteasome caused by MG-132 and ALLN or bortezomib, respectively. We also tested other antioxidants, and we found that vitamin C inhibited bortezomib-induced cell death. Similar to tiron, vitamin C inhibited cell death by blocking the ability of bortezomib to inhibit the proteasome. Until now, all the antioxidants that blocked proteasome inhibitor-induced cell death also blocked the proteasome inhibitor mechanism of action.

  16. Assessing endometrial hyperplasia and carcinoma treated with progestin therapy.

    PubMed

    Mentrikoski, Mark J; Shah, Akeesha A; Hanley, Krisztina Z; Atkins, Kristen A

    2012-10-01

    The effects of increased amounts of progesterone on the endometrium, including such features as eosinophilic cytoplasmic metaplasia, glandular atrophy, and decidualized stroma, are well-known among surgical pathologists. These changes are typically seen as secondary effects of pregnancy or exogenous hormone therapy for birth control purposes or abnormal bleeding. Treatment with progesterone has become a viable alternative to hysterectomy in some patients with complex atypical hyperplasia (CAH) and well-differentiated endometrial carcinoma (WDC), especially those who are poor surgical candidates or those wishing to preserve fertility. To date, only 1 study has specifically examined the effects of progestin therapy on patients with a previous diagnosis of CAH or WDC. That study proposed a classification scheme for the assessment of treated CAH and WDC. The authors concluded that after 6 months of treatment, endometrial biopsy findings of persistent cytologic atypia and architectural abnormalities were associated with treatment failure. This current study aims to assess the previously proposed criteria in a cohort of 30 patients (18 with a diagnosis of CAH and 12 with a diagnosis of WDC), and determine the usefulness of these criteria in clinical practice. Our study confirms that cytologic atypia after 6 months of therapy is strongly associated with treatment failure, and should be an indication to pursue definitive surgical treatment in these patients.

  17. Glycan profiling of endometrial cancers using lectin microarray.

    PubMed

    Nishijima, Yoshihiro; Toyoda, Masashi; Yamazaki-Inoue, Mayu; Sugiyama, Taro; Miyazawa, Masaki; Muramatsu, Toshinari; Nakamura, Kyoko; Narimatsu, Hisashi; Umezawa, Akihiro; Mikami, Mikio

    2012-10-01

    Cell surface glycans change during the process of malignant transformation. To characterize and distinguish endometrial cancer and endometrium, we performed glycan profiling using an emerging modern technology, lectin microarray analysis. The three cell lines, two from endometrial cancers [well-differentiated type (G1) and poorly differentiated type (G3)] and one from normal endometrium, were successfully categorized into three independent groups by 45 lectins. Furthermore, in cancer cells, a clear difference between G1 and G3 type was observed for the glycans recognized with six lectins, Ulex europaeus agglutinin I (UEA-I), Sambucus sieboldiana agglutinin (SSA), Sambucus nigra agglutinin (SNA), Trichosanthes japonica agglutinin I (TJA-I), Amaranthus caudatus agglutinin (ACA), and Bauhinia purpurea lectin (BPL). The lectin microarray analysis using G3 type tissues demonstrated that stage I and stage III or IV were distinguished depending on signal pattern of three lectins, Dolichos biflorus agglutinin (DBA), BPL, and ACA. In addition, the analysis of the glycans on the ovarian cancer cells showed that only anticancer drug-sensitive cell lines had almost no activities to specific three lectins. Glycan profiling by the lectin microarray may be used to assess the characteristics of tumors and potentially to predict the success of chemotherapy treatment.

  18. Polymorphisms in cyclooxygenase-2 gene in endometrial cancer patients.

    PubMed

    Torricelli, Federica; Mandato, Vincenzo Dario; Farnetti, Enrico; Abrate, Martino; Casali, Bruno; Ciarlini, Gino; Pirillo, Debora; Gelli, Maria Carolina; Costagliola, Luigi; Nicoli, Davide; Palomba, Stefano; La Sala, Giovanni Battista

    2015-09-01

    The enzyme cyclooxygenase 2 is an inducible enzyme expressed at sites of inflammation and in a variety of malignant solid tumors such as endometrial cancer (EC). In EC patients, its over-expression is correlated with progressive disease and poor prognosis. The expression is encoded by a polymorphic gene, called PTGS2. The aim of the current study was to test the hypothesis that rs5275 polymorphism of PTGS2 influence the prognosis of EC patients. This paper is a retrospective cohort study. Clinical and pathological data were extrapolated and genotypes were assessed on formalin-fixed and paraffin-embedded non-tumor tissues. A total of 159 type I EC patients were included in the final analysis. Univariate analysis indicated that patients with rs5275 genotype CC have a lower risk to develop a grade (G) 2-3 endometrial cancer. rs5275 effect on EC grading was confirmed by multivariate analysis also after data adjusting for age, BMI, parity, hypertension, and diabetes. Adjusted odds ratio (OR) confirmed that patients with rs5275 genotype CC have a risk 80 % lower (OR = 0.20, P = 0.009) to develop a G2 and/or G3 EC in comparison with patients with TT or TC genotype. Differentiation of the type 1 EC is significantly and independently influenced by rs5275 polymorphism. rs5275 CC patients have a lower risk to present a G2-G3 EC.

  19. Chemoresistance and targeted therapies in ovarian and endometrial cancers

    PubMed Central

    Brasseur, Kevin; Gévry, Nicolas; Asselin, Eric

    2017-01-01

    Gynecological cancers are known for being very aggressive at their advanced stages. Indeed, the survival rate of both ovarian and endometrial cancers is very low when diagnosed lately and the success rate of current chemotherapy regimens is not very efficient. One of the main reasons for this low success rate is the acquired chemoresistance of these cancers during their progression. The mechanisms responsible for this acquired chemoresistance are numerous, including efflux pumps, repair mechanisms, survival pathways (PI3K/AKT, MAPK, EGFR, mTOR, estrogen signaling) and tumor suppressors (P53 and Par-4). To overcome these resistances, a new type of therapy has emerged named targeted therapy. The principle of targeted therapy is simple, taking advantage of changes acquired in malignant cancer cells (receptors, proteins, mechanisms) by using compounds specifically targeting these, thus limiting their action on healthy cells. Targeted therapies are emerging and many clinical trials targeting these pathways, frequently involved in chemoresistance, have been tested on gynecological cancers. Despite some targets being less efficient than expected as mono-therapies, the combination of compounds seems to be the promising avenue. For instance, we demonstrate using ChIP-seq analysis that estrogen downregulate tumor suppressor Par-4 in hormone-dependent cells by directly binding to its DNA regulatory elements and inhibiting estrogen signaling could reinstate Par-4 apoptosis-inducing abilities. This review will focus on the chemoresistance mechanisms and the clinical trials of targeted therapies associated with these, specifically for endometrial and ovarian cancers. PMID:28008141

  20. Uterine leiomyomas: effects on architectural, cellular, and molecular determinants of endometrial receptivity.

    PubMed

    Makker, Annu; Goel, Madhu Mati

    2013-06-01

    Impaired endometrial receptivity is an important contributing factor to implantation failure. Uterine leiomyomas are widely prevalent steroid hormone-dependent benign tumors that act as a restraint to conception and successful outcome of pregnancies. Reports are available, which suggest that leiomyomas have negative influence on endometrial receptivity to blastocyst implantation. The aim of the present review is to provide a comprehensive picture of the current knowledge of the effect of uterine leiomyomas on the architectural, cellular, and molecular determinants of endometrial receptivity. Understanding the potential role of these factors will provide insight into the underlying mechanisms of leiomyoma-associated infertility and provide new areas for basic and translational research.

  1. Association between diabetes, diabetes treatment and risk of developing endometrial cancer.

    PubMed

    Luo, J; Beresford, S; Chen, C; Chlebowski, R; Garcia, L; Kuller, L; Regier, M; Wactawski-Wende, J; Margolis, K L

    2014-09-23

    A growing body of evidence suggests that diabetes is a risk factor for endometrial cancer incidence. However, most of these studies used case-control study designs and did not adjust for obesity, an established risk factor for endometrial cancer. In addition, few epidemiological studies have examined the association between diabetes treatment and endometrial cancer risk. The objective of this study was to assess the relationships among diabetes, diabetes treatment and endometrial cancer risk in postmenopausal women participating in the Women's Health Initiative (WHI). A total of 88 107 postmenopausal women aged 50-79 years who were free of cancer and had no hysterectomy at baseline were followed until date of endometrial cancer diagnosis, death, hysterectomy or loss to follow-up, whichever came first. Endometrial cancers were confirmed by central medical record and pathology report review. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios (HRs) (95% confidence interval (CI)) for diagnosis of diabetes and metformin treatment as risk factors for endometrial cancer. Over a mean of 11 years of follow-up, 1241 endometrial cancers developed. In the primary analysis that focused on prevalent diabetes at enrolment, compared with women without diabetes, women with self-reported diabetes, and the subset of women with treated diabetes, had significantly higher risk of endometrial cancer without adjusting for BMI (HR=1.44, 95% CI: 1.13-1.85 for diabetes, HR=1.57, 95% CI: 1.19-2.07 for treated diabetes). However after adjusting for BMI, the associations between diabetes, diabetes treatment, diabetes duration and the risk of endometrial cancer became non-significant. Elevated risk was noted when considering combining diabetes diagnosed at baseline and during follow-up as time-dependent exposure (HR=1.31, 95% CI: 1.08-1.59) even after adjusting for BMI. No significant association was observed between metformin use and endometrial cancer

  2. Single-cell transcriptome analysis of endometrial tissue.

    PubMed

    Krjutškov, K; Katayama, S; Saare, M; Vera-Rodriguez, M; Lubenets, D; Samuel, K; Laisk-Podar, T; Teder, H; Einarsdottir, E; Salumets, A; Kere, J

    2016-04-01

    How can we study the full transcriptome of endometrial stromal and epithelial cells at the single-cell level? By compiling and developing novel analytical tools for biopsy, tissue cryopreservation and disaggregation, single-cell sorting, library preparation, RNA sequencing (RNA-seq) and statistical data analysis. Although single-cell transcriptome analyses from various biopsied tissues have been published recently, corresponding protocols for human endometrium have not been described. The frozen-thawed endometrial biopsies were fluorescence-activated cell sorted (FACS) to distinguish CD13-positive stromal and CD9-positive epithelial cells and single-cell transcriptome analysis performed from biopsied tissues without culturing the cells. We studied gene transcription, applying a modern and efficient RNA-seq protocol. In parallel, endometrial stromal cells were cultured and global expression profiles were compared with uncultured cells. For method validation, we used two endometrial biopsies, one from mid-secretory phase (Day 21, LH+8) and another from late-secretory phase (Day 25). The samples underwent single-cell FACS sorting, single-cell RNA-seq library preparation and Illumina sequencing. Here we present a complete pipeline for single-cell gene-expression studies, from clinical sampling to statistical data analysis. Tissue manipulation, starting from disaggregation and cell-type-specific labelling and ending with single-cell automated sorting, is managed within 90 min at low temperature to minimize changes in the gene expression profile. The single living stromal and epithelial cells were sorted using CD13- and CD9-specific antibodies, respectively. Of the 8622 detected genes, 2661 were more active in cultured stromal cells than in biopsy cells. In the comparison of biopsy versus cultured cells, 5603 commonly expressed genes were detected, with 241 significantly differentially expressed genes. Of these, 231 genes were up- and 10 down-regulated in cultured cells

  3. Single-cell transcriptome analysis of endometrial tissue

    PubMed Central

    Krjutškov, K.; Katayama, S.; Saare, M.; Vera-Rodriguez, M.; Lubenets, D.; Samuel, K.; Laisk-Podar, T.; Teder, H.; Einarsdottir, E.; Salumets, A.; Kere, J.

    2016-01-01

    STUDY QUESTION How can we study the full transcriptome of endometrial stromal and epithelial cells at the single-cell level? SUMMARY ANSWER By compiling and developing novel analytical tools for biopsy, tissue cryopreservation and disaggregation, single-cell sorting, library preparation, RNA sequencing (RNA-seq) and statistical data analysis. WHAT IS KNOWN ALREADY Although single-cell transcriptome analyses from various biopsied tissues have been published recently, corresponding protocols for human endometrium have not been described. STUDY DESIGN, SIZE, DURATION The frozen-thawed endometrial biopsies were fluorescence-activated cell sorted (FACS) to distinguish CD13-positive stromal and CD9-positive epithelial cells and single-cell transcriptome analysis performed from biopsied tissues without culturing the cells. We studied gene transcription, applying a modern and efficient RNA-seq protocol. In parallel, endometrial stromal cells were cultured and global expression profiles were compared with uncultured cells. PARTICIPANTS/MATERIALS, SETTING, METHODS For method validation, we used two endometrial biopsies, one from mid-secretory phase (Day 21, LH+8) and another from late-secretory phase (Day 25). The samples underwent single-cell FACS sorting, single-cell RNA-seq library preparation and Illumina sequencing. MAIN RESULTS AND THE ROLE OF CHANCE Here we present a complete pipeline for single-cell gene-expression studies, from clinical sampling to statistical data analysis. Tissue manipulation, starting from disaggregation and cell-type-specific labelling and ending with single-cell automated sorting, is managed within 90 min at low temperature to minimize changes in the gene expression profile. The single living stromal and epithelial cells were sorted using CD13- and CD9-specific antibodies, respectively. Of the 8622 detected genes, 2661 were more active in cultured stromal cells than in biopsy cells. In the comparison of biopsy versus cultured cells, 5603

  4. The levels of the sex hormones are not different between type 1 and type 2 endometrial cancer.

    PubMed

    Wan, Jiayi; Gao, Yifei; Zeng, Ke; Yin, Yongxiang; Zhao, Min; Wei, Jia; Chen, Qi

    2016-12-21

    The involvement of hormonal factors in developing endometrial cancer is well documented. In particular, excess or unopposed estrogen is a major risk factor. Endometrial cancer is divided into estrogen-dependent and estrogen-independent types. Studies suggested that the subtypes of endometrial cancer share many common risk factors. Whether the levels of sex hormones differ between types 1 and 2 endometrial cancer has not been investigated. In this study, levels of estrogen, progesterone, testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) were investigated between type 1 and type 2 endometrial cancer taking into account menopausal status and parity. The sex hormones levels and estrogen and progesterone receptors were measured in 187 women with endometrial cancer. The levels of estradiol (E2), progesterone, testosterone, FSH and LH were not different between the subtypes of endometrial cancer regardless of menopausal status. In addition, the sex hormones were not different between patients of different party regardless of the menopausal status. The majority of type 1 (96%) and type 2 (82%) endometrial cancers were estrogen and progesterone receptor positive. Our data suggest that type 2 endometrial cancer is not completely estrogen independent, and type 1 and type 2 endometrial cancers may have a similar pathogenesis.