Endometrial (Uterus) Cancer
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Endometrial cancer is a malignancy of the endometrium (the inner lining of the uterus, or womb) and is the most common gynaecological cancer, and accounts for 13% of all cancers in women. It is most frequently in women over age 50. A know risk factor is prior oestrogen-replacement therapy (however, oestrogen replacement also lowers risk of heart disease). Symptoms can include pelvic pain, and blood-soaked discharge - though these are also common symptoms related to menopausal changes.

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Information for Patients and the Public
Information for Health Professionals / Researchers
Latest Research Publications

Information Patients and the Public (10 links)

Information for Health Professionals / Researchers (10 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Tomica D, Ramić S, Danolić D, et al.
A correlation between the expression of estrogen receptors and progesterone receptors in cancer cells and in the myometrium and prognostic factors in endometrial cancer.
Coll Antropol. 2014; 38(1):129-34 [PubMed] Related Publications
Endometrial cancer is the most common gynecological malignancy in Croatia. The aim of this study was to determine the immunohistochemical expression of estrogen receptors (ER) and progesterone receptors (PGR) in cancer cells and in the myometrium and to correlate it with prognostic factors of endometrial carcinoma. ER positivity in carcinoma cell nuclei was found in 42 cases (73.7%) and PGR positivity was found in 39 cases (68.4%). Loss of ER in carcinoma cell nuclei correlated with larger tumor size (p = 0.041), poor carcinoma differentiation (p = 0.012), a more aggressive histological type (p < 0.001), lymphovascular space invasion (p = 0.002) and a higher surgical stage (p = 0.037). Loss of PGR in carcinoma cell nuclei correlated with an increased age in patients (p = 0.009), poor tumor differentiation (p = 0.002), a more aggressive histological type (p < 0.001), lymphovascular space invasion (p = 0.002) and a higher surgical stage (p < 0.001). The lower expression of both receptors did not correlate with the depth of myometrial invasion. Regarding the status of receptors in the myometrium, loss of PGR in the myometrium correlated with a more aggressive histological type (p = 0.005) and a lack of ER in the myometrium tended to correlate with tumor growth (p = 0.059). In conclusion, the loss of both hormone receptors in carcinoma cells and loss of PGR in the myometrium was a predictor of a more aggressive type of endometrial cancer and a poor prognosis.

Cruz-Galarza D, Pérez-Rodríguez O, Laboy-Torres J, Gutiérrez-Rivera S
An unusual case of a borderline Brenner tumor associated with bilateral serous cystadenoma and endometrial carcinoma.
Bol Asoc Med P R. 2014; 106(1):54-6 [PubMed] Related Publications
Brenner tumor accounts for 1.5 to 2.5% of ovarian tumors. Nearly all are benign and 1% malignant. Less than twenty-five cases of borderline Brenner tumor have been reported worldwide. Our case is the first one related to a bilateral ovarian serous cystadenofibroma and endometrioid adenocarcinoma. This unusual case increases the limited data for borderline Brenner tumors.

Related: Breast Cancer Ovarian Cancer

Popovic MD, Banicevic AC, Popovic B, et al.
Treatment of endometrial cancer in patient with malignant obesity.
Med Arch. 2014; 68(1):69-70 [PubMed] Related Publications
Our 60-year-old patient menarche in 13-year, two delivery, last menstruation in 53-year, without uterine bleeding or any kind of symptomatology. The gynecological transvaginal ultrasound examination showed hyperplasio endometrii (20 mm). After curettage, pathological examination was diagnostic polypus carcinomatoides. The patient with HTA and obesity was admitted to and operated on at the Gynecological Department due to endometrial carcinoma (FIGO stage IA1). Because of her giant obesity, BMI - 71.50 kg/m2, weight 219 kg and height 175 cm, surgery by the abdominal approach was very difficult to perform, so vaginal hysterectomy was carried out. The procedure was completed within 127 minutes without any intraoperative complications. Blood loss was less than 100 ml. The patient was discharged on postoperative day 7. The patient was followed up for 6 months after surgery. No complications or recurrence were reported during the 6-month follow up.

Masui K, Yoshida K, Takenaka T, et al.
A novel minimally invasive technique of high-dose rate image-based intracavitary brachytherapy for endometrial cancer using a single fine and soft, flexible applicator.
Anticancer Res. 2014; 34(5):2537-40 [PubMed] Related Publications
AIM: We report on a minimally invasive computed tomography (CT)/magnetic resonance imaging (MRI)-based image-guided intracavitary brachytherapy (ICBT) for an elder patient with endometrial cancer, who was unfit for anesthesia, using a fine and soft flexible applicator.
PATIENTS AND METHODS: The patient was an 82-year-old female. She was identified as having T1bN0M0 (stage IB) tumor, and histological findings revealed grade 2 adenocarcinoma. She was contraindicated for surgery because of advanced age and severe pulmonary emphysema; therefore, she was managed with CT/MRI-based ICBT alone. The total treatment dose was 26 Gy (6.5 Gy per fraction). The dose-volume histogram of the gross tumor volume, the clinical target volume, and organs at risk were calculated.
RESULTS: The patient safely completed the ICBT course without pre-medication. Tumor growth was controlled, with complete disappearance after 32 months. No acute or late adverse effects were observed. MRI-guided ICBT can visualize the gross tumor volume in the uterine body, which cannot be detected by CT.
CONCLUSION: We successfully and safely performed minimally invasive CT/MRI-based ICBT without pre-medication in a patient with endometrial cancer with high surgical risks, using a fine and soft, flexible applicator.

Related: Brachytherapy

Tinelli R, Litta P, Meir Y, et al.
Advantages of laparoscopy versus laparotomy in extremely obese women (BMI>35) with early-stage endometrial cancer: a multicenter study.
Anticancer Res. 2014; 34(5):2497-502 [PubMed] Related Publications
BACKGROUND: The aim of the present study was to demonstrate the advantages of laparoscopy versus laparotomy for treatment of extremely obese women with early-stage endometrial cancer.
MATERIALS AND METHODS: Seventy-five extremely obese patients with Body Mass Index >35 kg/m(2) and clinical stage I endometrial cancer underwent hysterectomy and bilateral salpingo-oophorectomy, and in all cases we performed systematic pelvic lymphadenectomy by laparoscopy (mean BMI of 38±7.3 kg/m(2)) or laparotomy (mean BMI of 39±8.1 kg/m(2)).
RESULTS: In two (4.4%) patients of the laparoscopy group we observed a port site haematoma that was resolved without a second surgery. In three patients of the laparotomy-group, we observed dehiscence of the abdominal suture with surgical site infection that was re-sutured.
CONCLUSION: Laparoscopy can be considered a safe and effective therapeutic procedure for managing early-stage endometrial cancer in extremely obese women with a lower complication rate, lower surgical site infection and postoperative hospitalization.

Nakao Y, Yamasaki F, Yokoyama M, et al.
Minimal deviation endometrioid adenocarcinoma of the endometrium and its MRI findings.
Eur J Gynaecol Oncol. 2014; 35(2):185-7 [PubMed] Related Publications
Minimal deviation endometrioid adenocarcinoma (MDA-E) of the endometrium is a rare pathological entity, and its radiological features are rarely documented. A 73-year-old Japanese woman was referred to the authors when an endometrial biopsy revealed moderately differentiated endometrioid adenocarcinoma. Preoperative radiological examinations, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) showed no evidence of cancer nests. In the hysterectomy specimen, mildly atypical glands were scattered throughout the entire depth of the myometrium, without stromal desmoplastic reaction, and a tiny focus of typical, ruptured, endometrioid adenocarcinoma glands was found in the atrophic endometrium. MRI had not been able to identify this unusual, scattered, myometrial invasion. It should be kept in mind that in cases showing Stage IA endometrial carcinoma without endometrial thickening on MRI, this rare form of invasion may be present.

Toptas T, Tasova-Yildirim G, Karaveli S, Simsek T
Malignant mixed Müllerian tumor with small cell neuroendocrine differentiation: a case report and review of the literature.
Eur J Gynaecol Oncol. 2014; 35(2):180-4 [PubMed] Related Publications
INTRODUCTION: Small cell neuroendocrine differentiation (NE) in malignant mixed Müllerian tumors (MMMTs) is a rare and unusual occurrence with very few previously reported cases. There is no consensus regarding its diagnosis, classification, and optimal treatment options.
CASE: The authors report a patient with endometrial MMMT and NE differentiation who initially received comprehensive surgery followed by adjuvant chemotherapy containing cisplatin and etoposide. She further underwent metastasectomy and received carboplatin and paclitaxel for the relapse. She is still alive 12 months after the diagnosis. The authors performed a review of literature in order to characterize the clinical phenotype. These patients have a very aggressive disease. Median life expectancy seems to be less than a year.
CONCLUSIONS: It is reasonable to perform comprehensive staging surgery followed by adjuvant chemotherapy irrespective to stage of the disease.

Goiri Little C, Ruiz Sautua R, Martínez Gallardo L, et al.
Chylous ascites after retroperitoneal aortocava lymphadenectomy for endometrial cancer: a case report.
Eur J Gynaecol Oncol. 2014; 35(2):178-9 [PubMed] Related Publications
This is a case report of chylous ascites after retroperitoneal aortocava lymphadenectomy for endometrial cancer. There are few reports of chylous ascites in gynecologic surgery. Treatment is primarily conservative. The present case was resolved with a low fat diet with medium-chain triglyceride (MCT) supplements and somatostatin IV.

Wong LF, Wahab NA, Gleeson N
Appendectomy with cytoreductive surgery for ovarian and type 2 endometrial carcinoma.
Eur J Gynaecol Oncol. 2014; 35(2):143-8 [PubMed] Related Publications
UNLABELLED: There is considerable variation within and between cancer centers in the practice of appendectomy as part of cytoreductive surgery for ovarian carcinoma and in the surgical staging of endometrial carcinoma. The purpose of this study was to determine the prevalence and the type of appendiceal pathology, the morbidity associated with appendectomy in gynaecologic cancer surgery.
MATERIALS AND METHODS: This is a retrospective review of all cytoreductive surgery for ovarian carcinoma and surgical staging for endometrial carcinoma with appendectomy over a four year period.
RESULTS: Two hundred and fifty-one patients (38 patients for endometrial carcinoma surgery and 213 patients for ovarian cytoreduction) had an appendectomy performed. Metastases to the appendix was present in 46 (23.2%) of primary ovarian carcinoma and one (2.6%) primary endometrial carcinosarcoma. The appendix was more likely to be involved in advanced stage ovarian cancer with positive peritoneal washings, omental deposits, grade 3 differentiation, and papillary serous histology. Sixteen (6.4%) co-incidental primary appendiceal tumours were detected. No postoperative morbidity specific to appendectomy was identified. One case of ovarian carcinoma was upstaged from IC to IIIA by the appendiceal metastases. There was no upstaging of disease in the endometrial carcinoma group.
DISCUSSION: Appendectomy is an integral part of ovarian cytoreductive surgery but the authors found it did not upstage the disease in a clinically significant manner. The incidence of co-incidental appendiceal primary tumours was high in this series and may add value to the procedure in preventing further surgeries. The absence of procedure related morbidity is reassuring. The authors recommend appendectomy for all ovarian staging surgery and its consideration in type 2 endometrial cancer.

Related: Gastrointestinal Carcinoid Tumours Ovarian Cancer

Taskiran C, Erdem O, Onan A, et al.
Maspin expression in endometrial hyperplasia and carcinoma, and its relation with angiogenesis.
Eur J Gynaecol Oncol. 2014; 35(2):134-9 [PubMed] Related Publications
AIM: The purpose of this study was to evaluate the maspin expression in endometrial hyperplasia and cancer, and also to investigate its relation with angiogenesis.
MATERIALS AND METHODS: A total of 19 women with complex atypical hyperplasia, 44 patients with simple hyperplasia without atypia, and 67 patients with endometrial carcinoma were included. Maspin expression was assessed by immunohistochemistry (IHC), and tested for possible significant relation with age, FIGO stage, histologic type, grade, depth of myometrial invasion (MI), lymphovascular space involvement (LVSI), lymph node metastasis, and overall survival (OS). Angiogenesis was determined by vascular endothelial growth factor (VEGF) staining.
RESULTS: Maspin expression was detected in only three patients with endometrial hyperplasia (5%). In patients with endometrial cancer, cytoplasmic and nuclear maspin expressions were detected in 36 (53.7%) and 18 (26.9%) patients, respectively. No significant relation was noted between staining localizations and prognostic variables. The five-year OS rate for patients with cytoplasmic staining was 91%, compared to 87% for patients without staining (p = 0.31). These values for nuclear expression were 100% and 87%, respectively (p = 0.16). The cytoplasmic and nuclear maspin expressions were found to be significantly correlated with VEGF (r = 0.278, p = 0.02 and r = 0.295, p = 0.01, respectively).
DISCUSSION: This is the first study to demonstrate the relation between maspin expression and angiogenesis in endometrial cancer. Although no survival difference was noted for cytoplasmic or nuclear maspin expressions, a tendency was detected for nuclear staining. Further series will clarify the exact prognostic role of maspin expression in gynecological malignancies including endometrial cancer.

Related: Angiogenesis and Cancer VEGFA SERPINB5

Koh YV, Tang JI, Choo BA, et al.
Adjuvant radiotherapy for endometrial cancer--a comparative review of radiotherapy technique with acute toxicity.
Eur J Gynaecol Oncol. 2014; 35(2):128-33 [PubMed] Related Publications
OBJECTIVES: The addition of pelvic radiotherapy to brachytherapy (EBRT-BT) in early-stage endometrial cancer is controversial and may cause unnecessary toxicity. The incidence of acute toxicity of EBRT-BT will have an impact on clinical decision and patient compliance but is currently poorly understood. This study compares the acute toxicities of EBRT-BT versus BT alone.
MATERIALS AND METHODS: Seventy-nine patients with FIGO Stage IA-II endometrial cancer who underwent adjuvant radiotherapy, (EBRT-BT or BT alone) from 2001 to 2011 were included in the study. Medical records of these patients were reviewed retrospectively and toxicity graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Patients were followed up for at least three months post-treatment to assess resolution of toxicity.
RESULTS: The mean age of the study group was 60.6 years. Median follow-up was four years. Forty patients received EBRT-BT. There was a 37% increase in Grade 1-3 diarrhea with the addition of pelvic radiotherapy (OR 18.67, p < 0.0005) and a 34% increase in lethargy (p < 0.0005). There was also an increased occurrence of genitourinary and skin toxicities. Two patients in the EBRT-BT group required hospitalisation for severe diarrhea and three patients were unable to complete the treatment. All acute toxicities had resolved by three months post treatment.
CONCLUSION: EBRT-BT causes significantly more acute toxicities compared to BT alone. Patients should be informed of this during counselling.

Related: Brachytherapy

Prakansamut N, Sirayapiwat P, Triratanachat S
The percentages of endometrial hyperplasia and endometrial cancer among polycystic ovary syndrome (PCOS) patients presenting with abnormal menstrual pattern.
J Med Assoc Thai. 2014; 97(2):159-64 [PubMed] Related Publications
OBJECTIVE: Assess the occurrence of endometrial hyperplasia and endometrial cancer among PCOS patients having abnormal menstrual pattern. Endometrial thickness and other clinical characteristics associated with endometrial hyperplasia and endometrial cancer were also evaluated
MATERIAL AND METHOD: Women with PCOS and abnormal menstrual pattern were enrolled into this cross-sectional study. Endometrial thicknesses were evaluated using transvaginal sonography. Endometrial aspiration was performed with endometrial aspirator and sent for pathology.
RESULTS: Out of 52 PCOS patients with abnormal menstrual pattern, nine (17.3%) and one (1.9%) had endometrial hyperplasia and endometrial cancer, respectively. There was no significant difference in mean endometrial thickness between those who had abnormal and normal endometrium (8.19 +/- 2.58 mm and 7.76 +/- 4.03 mm, respectively). However BMI and age of patients with abnormal endometrium were significantly higher and older than those with normal endometrium (p = 0.031 and p = 0.009, respectively).
CONCLUSION: Nineteen point two percent (19.2%) of patients with PCOS and abnormal menstrual pattern had endometrial hyperplasia or endometrial cancer Endometrial thickness was not different between those with abnormal and normal endometrium.

Related: Thailand

Mozos A, Catasús L, D'Angelo E, et al.
The FOXO1-miR27 tandem regulates myometrial invasion in endometrioid endometrial adenocarcinoma.
Hum Pathol. 2014; 45(5):942-51 [PubMed] Related Publications
Micro-RNA (miRNA) signatures influence the prognosis of cancer, but little is known about their role in myometrial invasion in endometrioid endometrial adenocarcinoma (EEC). We studied miRNA expression signatures in noninvasive and invasive EEC focusing on the alteration of miR-27 and its main target, FOXO1 as well as their relationship with the clinicopathological parameters and other genetic alterations such as PIK3CA mutations. In 25 tumors and 5 normal endometria, unsupervised hierarchical clustering analysis showed that normal endometria and noninvasive EEC were grouped together and separately from invasive and advanced stage tumors. Of the 20 miRNAs differentially expressed in noninvasive (stage IA) and myoinvasive adenocarcinomas (stage IB and IC), miR27 was overexpressed in invasive adenocarcinomas, and its expression increased linearly according to stage. Results were validated by quantitative real-time reverse transcription polymerase chain reaction in an independent series of 44 EEC. By in situ hybridization, miR-27 expression was limited to the stroma. Using quantitative real-time reverse transcription polymerase chain reaction, the expression of proapoptotic transcription factor FOXO1 was down-regulated in invasive compared with noninvasive tumors. Furthermore, we found that the expression of active caspase 3 was higher in noninvasive than invasive EEC. When stratified by PIK3CA mutations, all invasive tumors down-regulated FOXO1, but only nonmutated adenocarcinomas showed miR-27 overexpression. In conclusion, we propose that the miR27-FOXO1 tandem inhibits apoptosis and represents an alternative pathway for tumor cell survival in PIK3CA-nonmutated EEC.

Căpîlna ME, Rusu SC, Szabo B, Marian C
Three synchronous primary pelvic cancers--a case report.
Rev Med Chir Soc Med Nat Iasi. 2014 Jan-Mar; 118(1):107-10 [PubMed] Related Publications
The occurrence of synchronous primary gynaecologic malignancies is a relatively common event. However, the occurrence of three different pelvic cancers is very rare. In this report, we describe the clinical, surgical and pathological findings of a patient with synchronous primary malignancies of the fallopian tube, endometrium and sigmoid colon. To our knowledge, it is the first case described in the literature with such an association of primary synchronous cancers.

Related: Carboplatin Fallopian Tube Cancer Ovarian Cancer

Sasamoto N, Ueda Y, Amemiya K, et al.
Endometrial adenocarcinoma arising in a Turner's syndrome patient with spontaneous menstruation: a case report.
J Reprod Med. 2014 Mar-Apr; 59(3-4):177-80 [PubMed] Related Publications
BACKGROUND: Women with Turner's syndrome exhibit anovulation, and the majority do not spontaneously menstruate. We present an unusual case of endometrial adenocarcinoma developing in a Turner's syndrome patient who was exhibiting spontaneous menstruation while not receiving regular hormone therapy.
CASE: The patient's karyotype from blood lymphocytes was a mosaic of 45,XO/ 46,XX. Menarche and sexual development were normal. Her menstrual cycle had been regular for one year, but then became noticeably irregular. At age 26 she was referred to our hospital after bleeding for almost 1 year. An endometrial adenocarcinoma was detected during performance of diagnostic endometrial curettage. A total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy was conducted. The final histological diagnosis was endometrial adenocarcinoma, Grade 1, pT1a N0 M0. Fluorescence in situ hybridization analysis of the right and left ovaries revealed a mosaic karyotype of 45,XO/ CONCLUSION: Previous reports regarding Turner's syndrome detected spontaneous menstruation in only 16% of patients; however, spontaneous menstruation was observed in 8 of 10 (80%) Turner's syndrome cases that developed endometrial carcinoma without receiving regular hormone therapy (p < 0.0001). Hormone therapy may be indicated for an irregular menstrual cycle in Turner's syndrome patients.

Bevis KS, Kilgore LC, Alvarez RD, et al.
Combination therapy with paclitaxel, carboplatin and megestrol acetate for the management of advanced stage or recurrent carcinoma of the endometrium: a phase II study.
J Reprod Med. 2014 Mar-Apr; 59(3-4):113-20 [PubMed] Related Publications
OBJECTIVE: To determine overall survival (OS), progression-free interval (PFI), and toxicity in patients with advanced stage or recurrent endometrial cancer (EMCA) treated with combination paclitaxel, carboplatin and megestrol acetate.
STUDY DESIGN: Patients with stage III/IV or recurrent EMCA were enrolled between October 2004 and April 2008 and received paclitaxel (175 mg/m2) and carboplatin (AUC 6) every 21 days for 6 cycles and megestrol acetate 40 mg orally 4 times daily for up to 5 years. Dose reductions were based on grade 3/4 hematologic toxicity. Survival was calculated from time of study enrollment.
RESULTS: A total of 28 patients were evaluable: 21 (75%) patients with stage III/IV disease and 7 (25%) with recurrent disease. Three patients with recurrence received prior radiation. Mean PFI was 40.2 months (29.7-50.6). Mean OS was 50.1 months (41.5-58.7). After a median 40.4 months (range, 5.6-68.4) of follow-up, 13 patients (46%) had no evidence of disease, 4 were alive with disease, and 10 were dead of disease. One patient died without evidence of disease. Twenty-three patients (82%) completed 6 cycles of chemotherapy. Ten patients experienced a dose reduction. Myelosuppression was common, with 22 patients (78%) experiencing grade 3/4 neutropenia and 6 patients (21%) experiencing grade 3/4 anemia. Three patients had a deep vein thrombosis. One patient experienced a pulmonary thromboembolus.
CONCLUSION: Combination therapy with paclitaxel, carboplatin and megestrol acetate demonstrates activity. Myelosuppression is common but can be managed with colony-stimulating factors. The addition of hormonal therapy to cytotoxic chemotherapy may improve survival.

Related: Carboplatin Paclitaxel

Shim SH, Lee SJ, Kim SN
Effects of hormone replacement therapy on the rate of recurrence in endometrial cancer survivors: a meta-analysis.
Eur J Cancer. 2014; 50(9):1628-37 [PubMed] Related Publications
BACKGROUND: To quantify the effect of hormone replacement therapy (HRT) on the recurrence in endometrial cancer (EC) survivors through a meta-analysis.
METHODS: A systematic literature review was conducted through October 2013 and included studies reporting estimates of effect size for the relationship between HRT use and the risk of EC recurrence. Study design features that may affect the selection of participants, the detection of EC recurrence and manuscript publication were assessed. If there was no significant statistical heterogeneity across studies, then a fixed effects model was used to obtain pooled estimates for the effect of HRT use on EC recurrence by combining study-specific estimates of the odds ratio (OR).
RESULTS: One randomised trial and five observational studies included 896 EC survivors who used HRT and 1079 non-users. Over the combined study period, 19 of the 896 HRT users experienced recurrence, whereas 64 of the 1079 controls did. The meta-analysis based on the fixed effects model indicates no significant increase in the risk of recurrence in EC survivors using HRT relative to the control group (OR: 0.53; 95% confidence interval: 0.30-0.96, I(2)=49.0). This pattern was also observed in the subgroup analysis for the stage and type of HRT. There was no evidence of any publication bias.
CONCLUSIONS: Although based mainly on observational studies, the literature does not provide support for a positive relationship between HRT use and the risk of EC recurrence. Future research should verify this relationship through randomised controlled trials over a longer term.

Lubián López DM, Orihuela López F, García-Berbel Molina L, et al.
Endometrial polyps in obese asymptomatic pre and postmenopausal patients with breast cancer: is screening necessary?
Gynecol Oncol. 2014; 133(1):56-62 [PubMed] Related Publications
OBJECTIVE: To evaluate the prevalence of endometrial polyps in obese asymptomatic pre and postmenopausal patients with breast cancer and to know if a baseline pretamoxifen endometrial assessment should be taken into consideration in these women at high risk.
METHODS: A cross-sectional study was carried out with 201 women with breast cancer. A diagnostic hysteroscopy was performed in all women. All formations suspected as polyps were removed. The prevalence of endometrial polyps was analyzed in all patients (n=182) and in premenopausal (n=49) and postmenopausal (n=118) women with estrogen receptor (ER) positive breast cancer (BC) according to their body mass index (BMI) and other risk factors.
RESULTS: Hysteroscopic evaluation was possible in 182 cases (90.5%). Of the total of women, 160 (87.9%) were ER(+)BC patients, 133 (73.1%) postmenopausal women and 41.5% were obese (BMI≥30kg/m(2)). Endometrial polyps were found in 52 cases (28.5%) (3 cases of simple hyperplasia harbored within a polyp). In premenopausal patients with ER(+)BC, there were no statistical differences in endometrial polyps according to their BMI (22.3% in non-obese women vs 31.7% in obese) while in all patients (26.4% in non-obese vs 44.0% in obese) and in postmenopausal women with ER(+)BC (25.9% in non-obese vs 48.6% in obese) there were statistical differences. In all women the relative risk (RR) of endometrial polyps in obese patients was 2.24 (1.01-4.83), in obese postmenopausal women with ER(+)BC was 2.75 (1.01-7.40) and in obese premenopausal patients with ER(+)BC was 1.42 (0.80-3.29).
CONCLUSIONS: Asymptomatic women with breast cancer have a high prevalence of baseline subclinical endometrial polyps and it is very high in obese postmenopausal patients with estrogen receptor positive breast cancer. Therefore, there may be a future role for baseline pretamoxifen screening of some sort for the obese asymptomatic postmenopausal patient, especially if they are elderly and ER positive.

Related: Breast Cancer Breast Cancer Screening

Basen-Engquist K, Carmack C, Brown J, et al.
Response to an exercise intervention after endometrial cancer: differences between obese and non-obese survivors.
Gynecol Oncol. 2014; 133(1):48-55 [PubMed] Article available free on PMC after 01/04/2015 Related Publications
OBJECTIVE: The objective of this paper is to describe baseline differences between obese and non-obese endometrial cancer survivor in anthropometrics, exercise behavior, fitness, heart rate and blood pressure, and quality of life, and to analyze whether the effect of a home-based exercise intervention on these outcomes differed for obese and non-obese participants.
METHODS: One hundred post-treatment Stage I-IIIa endometrial cancer survivors participated in a single arm 6month study in which they received a home-based exercise intervention. Cardiorespiratory fitness, anthropometrics, and exercise behavior were measured every two months, and quality of life (QOL) and psychological distress were measured at baseline and 6months.
RESULTS: Adjusting for potential confounders, at baseline obese survivors had poorer cardiorespiratory fitness (p=.002), higher systolic blood pressure (p=.018), and lower physical functioning (p<.001) and ratings of general health (p=.002), and more pain (p=.037) and somatization (.002). Significant improvements were seen in exercise behavior, resting heart rate, systolic blood pressure, and multiple QOL domains over the course of the intervention. Obese survivors had less improvement in exercise behavior and cardiorespiratory fitness than non-obese survivors, but there were no differences with regard to improvements in QOL and stress.
CONCLUSIONS: Home based exercise interventions are beneficial to endometrial cancer survivors, including those whose BMI is in the obese range. While obese survivors have lower levels of physical activity and fitness, they experienced similar activity, fitness, quality of life and mental health benefits. Exercise should be encouraged in endometrial cancer survivors, including those who are obese.

Cote ML, Ruterbusch JJ, Ahmed Q, et al.
Endometrial cancer in morbidly obese women: do racial disparities affect surgical or survival outcomes?
Gynecol Oncol. 2014; 133(1):38-42 [PubMed] Related Publications
OBJECTIVE: Endometrial cancer mortality disproportionately affects black women and whether greater prevalence of obesity plays a role in this disparity is unknown. We examine the effect of race on post-surgical complications, length of stay, and mortality specifically in a morbidly obese population.
METHODS: Black and white women with endometrial cancer diagnosed from 1996 to 2012 were identified from the University Pathology Group database in Detroit, Michigan, and records were retrospectively reviewed to obtain clinicopathological, demographic, and surgical information. Analysis was limited to those with a body mass index of 40kg/m(2) or greater. Differences in the distribution of variables by race were assessed by chi-squared tests and t-tests. Kaplan-Meier and Cox regression analyses were performed to examine factors associated with mortality.
RESULTS: 97 white and 89 black morbidly obese women were included in this analysis. Black women were more likely to have type II tumors (33.7% versus 15.5% of white women, p-value=0.003). Hypertension was more prevalent in black women (76.4% versus 58.8%, p-value=0.009), and they had longer hospital stays after surgery despite similar rates of open vs minimally invasive procedures and lymph node dissection (mean days=5.4) compared to whites (mean days=3.5, p-value=0.036). Wound infection was the most common complication (16.5% in whites and 14.4% in blacks, p-value=0.888). Blacks were more likely to suffer other complications, but overall the proportions did not differ by race. In univariate analyses, black women had higher risk of endometrial cancer-related death (p-value=0.090). No racial differences were noted in adjusted survival analyses.
CONCLUSION: A more complete investigation, incorporating socio-demographic factors, is warranted to understand the effects of morbid obesity and race on endometrial cancer.

Gonthier C, Walker F, Luton D, et al.
Impact of obesity on the results of fertility-sparing management for atypical hyperplasia and grade 1 endometrial cancer.
Gynecol Oncol. 2014; 133(1):33-7 [PubMed] Related Publications
OBJECTIVES: The aim of the present study was to evaluate the impact of obesity on reproductive and oncologic outcomes on the success of fertility-sparing management.
METHODS: This retrospective multicenter cohort study included women treated conservatively for atypical hyperplasia (AH) and endometrial cancer (EC) to preserve fertility. Five inclusion criteria were defined: (i) the presence of AH or grade 1 EC confirmed by two pathologists; (ii) adequate radiological examination before conservative management; (iii) available body mass index (BMI) at the beginning of treatment; and (iv) a minimum follow-up time of six months.
RESULTS: Forty patients fulfilled the inclusion criteria (17 had EC, and 23 had AH), mean age and BMI were 33 years and 29kg/m(2) respectively. Among the 15 obese patients, after medical treatment, 10 patients responded (67%) and three relapsed, whereas in the 25 non-obese patients, 19 responded (76%) and three relapsed (p=0.72). The overall pregnancy rate and follow-up time were 35% and 35 months respectively. Among the 15 obese patients, after medical treatment, two patients became pregnant, whereas in the 25 non-obese patients, 12 became pregnant (p=0.04).
CONCLUSION: Despite similar response and recurrence rates, our results suggest that fertility-sparing management for AH and EC is associated with a lower probability of pregnancy in obese patients.

Ko EM, Walter P, Clark L, et al.
The complex triad of obesity, diabetes and race in Type I and II endometrial cancers: prevalence and prognostic significance.
Gynecol Oncol. 2014; 133(1):28-32 [PubMed] Related Publications
BACKGROUND: We examined the distribution of obesity, diabetes, and race in Type I and Type II endometrial cancers (EC) and their associations with clinical outcomes.
METHODS: A multi-institutional retrospective analysis of Type I and II EC cases from January 2005 to December 2010 was conducted. Type I (endometrioid), Type II (serous and clear cell), low grade (LG) (grade 1 and 2 endometrioid), and high grade (HG) (grade 3 endometrioid, serous, clear cell) cohorts were compared. Univariate and multivariate analyses were used to determine time-to-recurrence (TTR), recurrence-free survival (RFS), and overall survival (OS).
RESULTS: Type I EC patients were more frequently obese than Type II (66% versus 51%, p<0.0001) and had similar rates of diabetes (25% versus 23%, p=0.69). African-Americans (AA) had higher median BMI than Caucasians in both Type I (p<0.001) and II (p<0.001) ECs, and were twice as likely to have diabetes (p<0.001). In Type I EC, DM was associated with worse RFS and OS in unadjusted and adjusted models (RFS HR 1.38, 95%CI 1.01-1.89; OS HR 1.86, 95%CI 1.30-2.67), but not with TTR. BMI was associated with improved TTR in the adjusted analysis for Type I EC (HR 0.98, 95%CI 0.95-1.0), but not with RFS or OS. There was no association between DM or BMI and outcomes in Type II or HG EC. AA race was not associated with RFS or OS on adjusted analyses in any group.
CONCLUSIONS: Obesity and diabetes are highly prevalent in Type I and II ECs, especially in AA. DM was associated with worse RFS and OS in Type I EC. Neither DM nor BMI was associated with outcomes in Type II or HG EC.

Owings RA, Quick CM
Endometrial intraepithelial neoplasia.
Arch Pathol Lab Med. 2014; 138(4):484-91 [PubMed] Related Publications
CONTEXT: Developed in conjunction with molecular and progression data, the sequence classification schema for endometrial intraepithelial neoplasia (EIN)/benign hyperplasia (BH) provides an easy to adopt and reproducible method for classification of endometrial biopsies.
OBJECTIVE: To review current data supporting the use of BH/EIN to classify endometrial biopsies, and to discuss the hormone-driven endometrial sequence from anovulation/disordered proliferative endometrium through BH and EIN and their diagnostic difficulty.
DATA SOURCES: A comprehensive review of EIN literature based on literature indexed by PubMed (National Library of Medicine) and Google Scholar.
CONCLUSIONS: The BH/EIN schema is gaining wider acceptance among pathologist and clinicians. The research leading to the EIN criteria is based on molecular and progression data. The BH/EIN schema has better reproducibility among pathologists, is intuitively easy to use, and requires understanding of endometrial physiology and neoplasia.

Related: PTEN

Nikolaou M, Kourea HP, Tzelepi V, et al.
The prognostic role of preoperative serum CA 125 levels in patients with endometrial carcinoma.
J BUON. 2014 Jan-Mar; 19(1):198-202 [PubMed] Related Publications
PURPOSE: Previous studies have shown that elevated preoperative serum CA 125 levels strongly correlate with various clinical and pathological variables and prognosis of patients with endometrial carcinoma (EC). The aim of the present study was to evaluate the clinical significance of preoperative serum CA 125 levels in patients with EC.
METHODS: A retrospective study of all EC patients treated at our institution between 1995 and 2010 with available follow-up was conducted. The preoperative serum level of CA 125 was measured in 99 patients and evaluated in relation to various clinical and pathological variables and outcome. We used the cut-off level of 20 U/ml for CA 125 on chi-square test for categorical variables. Survival analysis was performed with the use of Kaplan Meier method, the log rank test and Cox proportional hazards regression analysis.
RESULTS: In the early stages of disease the mean values of CA 125 were 35 U/ml (SD±70) for stages IA-IB and 21 U/ml (SD±29) for stage IC (Mann-Whitney test for continuous variables). In advanced stages of disease (III-IV), the values of preoperative serum CA 125 levels were statistically increased, with mean value 54 U/ml (SD±44), in comparison to stages IA-IB (p=0.02) and IC (p=0.007). According to the multivariate analysis, elevated preoperative serum CA 125 level (p=0.043) and histological tumor type (p=0.004) were independent prognostic factors for disease free survival (DFS) and overall survival (OS) of patients with EC.
CONCLUSION: The current study suggests that measurement of preoperative serum CA 125 is a useful clinical tool in the prognosis of patients with EC.

Zhao Q, Bian AP, Zhang Y, et al.
Expression of budding uninhibited by benzimidazoles-1 and mitotic arrest deficient-2 in endometrial carcinoma and its significance.
Eur J Gynaecol Oncol. 2014; 35(1):44-7 [PubMed] Related Publications
OBJECTIVE: The aim of this study was to explore the expression of budding uninhibited by benzimidazoles-1 (Bub1) and mitotic arrest deficient-2 (Mad2) in endometrial carcinoma and its significance.
MATERIALS AND METHODS: The expression of Bub 1 and Mad2 in 30 human normal endometrial tissues (group A), 30 complexly-hyperplastic endometrial tissues (group B), and 63 endometrial carcinoma tissues (group C) was observed using immunohistochemistry (the streptavidin-peroxidase method).
RESULTS: The positive expression rates of Bub1 in groups A, B, and C were 86.67%, 56.67%, and 28.57%, respectively. The positive rate of Bub1 protein was correlated with the differentiation degree and clinical stage of endometrial carcinoma (p < 0.05) other than lymph node metastasis (p > 0.05): A higher differentiation degree and a more advanced stage of endometrial carcinoma indicated a higher positive rate of Bub1 protein. The positive rates of Mad2 protein in groups A, B, and C were 23.33%, 56.67%, and 85.71%, respectively. The positive rate of Mad2 protein was correlated with the differentiation degree of endometrial carcinoma (p < 0.05) other than its clinical stage and lymph node metastasis (p > 0.05): A lower differentiation degree indicated a higher positive rate of Mad2 protein. Bub1 and Mad2 proteins were negatively correlated in the endometrial carcinoma tissues (r = - 0.719, p < 0.001).
CONCLUSION: Bub1 and Mad2 proteins interact with each other. They may play an important role in the initiation and development of endometrial carcinoma.

Kataoka H, Mori T, Yamamoto T, et al.
Outcome of fertility-sparing treatment with medroxyprogesterone acetate for atypical hyperplasia and endometrial carcinoma in young Japanese women.
Eur J Gynaecol Oncol. 2014; 35(1):11-5 [PubMed] Related Publications
PURPOSE: To review the outcome in patients with atypical endometrial hyperplasia (AEH) and endometrial cancer (EC) who received MPA treatment in the present hospital.
MATERIALS AND METHODS: Patients with AEH or EC were administered MPA for 12 weeks followed by endometrial curettage. The rates of effect, recurrence, pregnancy, and complications were evaluated. The changes in progesterone receptors and FOXO-1, known as a target of MPA treatment, were examined by immunostaining.
RESULTS: Four of seven patients with endometrial cancer and three of three patients with AH had complete response. Four of seven patients had recurred within one year after the treatment and had to undergo hysterectomy. None of the patients showed changes in progesterone receptors. Although six of seven patients were negative for FOXO-1 before and after treatment, all the patients showed increased developments of FOXO-1 during MPA treatment.
CONCLUSION: Progestin as a fertility-preserving treatment is expected to be effective for endometrial cancer, but judicious use might be required because it shows high rate of recurrence. Further studies regarding the mechanism may be necessary to achieve high efficacy.

Dewdney SB, Jiao Z, Roma AA, et al.
The prognostic significance of lymphovascular space invasion in laparoscopic versus abdominal hysterectomy for endometrioid endometrial cancer.
Eur J Gynaecol Oncol. 2014; 35(1):7-10 [PubMed] Related Publications
INTRODUCTION: Recent reports have suggested that uterine manipulators can induce lymphovascular space involvement (LVSI) by endometrial cancer in laparoscopic hysterectomy specimens. The prognostic significance of this phenomenon known as "vascular pseudo invasion" remains elusive.
MATERIALS AND METHODS: The authors conducted a retrospective, single institution study of patients who underwent initial surgery for grade 1 and grade 2 endometrioid endometrial cancers with LVSI. Cases were stratified by surgical approach (laparoscopy vs laparotomy). Clinicopathologic and procedure characteristics as well as outcome data were analyzed. Univariate and multivariate analyses were performed. Disease-free survival (DFS) was analyzed using the Kaplan-Meier product limit method.
RESULTS: A total of 104 cases (20 laparoscopic, 84 laparotomy) were analyzed. Mean age (65 vs 64 years, respectively), stage distribution, mean number of lymph nodes sampled (18 vs 21, respectively) and use of adjuvant therapy was similar for both groups (p > 0.05). Mean body mass index (BMI) was 30 vs 35 kg/m2, respectively (p = 0.002). Mean follow up was 24 months (range 0.1-102). Univariate analysis demonstrated that LVSI in the laparoscopic setting was associated with worse DFS (p = 0.002). After adjusting for grade the risk of recurrence remained higher for laparoscopic cases (HR: 15.7, 95% CI 1.7-140.0, p = 0.014).
CONCLUSIONS: Adjusted risk of recurrence associated with LVSI is higher in cases approached laparoscopically arguing against the concept of "vascular pseudo invasion" associated with the use of uterine manipulators and balloons. LVSI should be regarded as a serious risk factor and taken into account for triage to adjuvant therapies, even in laparoscopically treated early-stage endometrial cancer.

Aristizabal P, Graesslin O, Barranger E, et al.
A suggested modification to FIGO stage I endometrial cancer.
Gynecol Oncol. 2014; 133(2):192-6 [PubMed] Related Publications
OBJECTIVE: FIGO stage I endometrial cancers are divided into two substages, regardless of the presence or absence of lymphovascular space invasion (LVSI). The aim of this study was to investigate whether stratification based on the LVSI status would better predict mortality.
METHODS: Using a multicentric database, we identified patients who underwent endometrial cancer operations between 2000 and 2010. The staging performance was quantified with respect to discrimination.
RESULTS: The study cohort included 508 patients (198 with LVSI-positive tumors and 310 with LVSI-negative tumors). The survival difference between the stage I patients with LVSI-positive and LVSI-negative tumors was highly significant (81% and 97%, respectively P=.009), whereas the difference between the stage I patients with tumors invading greater or less than half of the myometrium was not (87% and 96%, respectively P=0.09). The 5-year OS rates for the patients with LVSI-negative tumors invading less than half of the myometrium, with LVSI-negative tumors invading more than half of the myometrium and with LVSI-positive invading more than or less than half of the myometrium were 98%, 95%, and 81%, respectively (P=.03). Separating the LVSI-negative and LVSI-positive tumors would improve discrimination (concordance index, 77% vs. 75%, respectively, using the actual staging system).
CONCLUSION: A LVSI-positive status has a significantly worse prognosis. In this study, the distinction by LVSI status appears to be more relevant than the distinction between stages IA and IB for predicting survival in stage I endometrial cancer. This difference in prognosis would favor restaging these two entities.

Rowlands IJ, Beesley VL, Janda M, et al.
Quality of life of women with lower limb swelling or lymphedema 3-5 years following endometrial cancer.
Gynecol Oncol. 2014; 133(2):314-8 [PubMed] Related Publications
OBJECTIVE: To quantitatively assess and compare the quality of life (QoL) of women with a self-reported diagnosis of lower limb lymphedema (LLL), to women with lower limb swelling (LLS), and to women without LLL or LLS following treatment for endometrial cancer.
METHODS: 1399 participants in the Australian National Endometrial Cancer Study were sent a follow-up questionnaire 3-5 years after diagnosis. Women were asked if they had experienced swelling in the lower limbs and, if so, whether they had received a diagnosis of lymphedema by a health professional. The 639 women who responded were categorized as: Women with LLL (n=68), women with LLS (n=177) and women without LLL or LLS (n=394). Multivariable-adjusted generalized linear models were used to compare women's physical and mental QoL by LLL status.
RESULTS: On average, women were 65 years of age and 4 years after diagnosis. Women with LLL had clinically lower physical QoL (M=41.8, SE=1.4) than women without LLL or LLS (M=45.1, SE=0.8, p=.07), however, their mental QoL was within the normative range (M=49.6; SE=1.1 p=1.0). Women with LLS had significantly lower physical (M=41.0, SE=1.0, p=.003) and mental QoL (M=46.8; SE=0.8, p<.0001) than women without LLL or LLS (Mental QoL: M=50.6, SE=0.8).
CONCLUSION: Although LLL was associated with reductions in physical QoL, LLS was related to reductions in both physical and mental QoL 3-5 years after cancer treatment. Early referral to evidence-based lymphedema programs may prevent long-term impairments to women's QoL.

Related: Australia

Bharati R, Jenkins MA, Lindor NM, et al.
Does risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair gene depend on family history of endometrial cancer or colorectal cancer?
Gynecol Oncol. 2014; 133(2):287-92 [PubMed] Article available free on PMC after 01/05/2015 Related Publications
OBJECTIVE: To determine whether risk of endometrial cancer for women without a germline mutation in a DNA mismatch repair (MMR) gene depends on family history of endometrial or colorectal cancer.
METHODS: We retrospectively followed a cohort of 79,166 women who were recruited to the Colon Cancer Family Registry, after exclusion of women who were relatives of a carrier of a MMR gene mutation. The Kaplan-Meier failure method was used to estimate the cumulative risk of endometrial cancer. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for association between family history of endometrial or colorectal cancer and risk of endometrial cancer.
RESULTS: A total of 628 endometrial cancer cases were observed, with mean age at diagnosis of 54.4 (standard deviation: 15.7) years. The cumulative risk of endometrial cancer to age 70 years was estimated to be 0.94% (95% CI 0.83-1.05) for women with no family history of endometrial cancer, and 3.80% (95% CI 2.75-4.98) for women with at least one first- or second-degree relative with endometrial cancer. Compared with women without family history, we found an increased risk of endometrial cancer for women with at least one first- or second-degree relative with endometrial cancer (HR 3.66, 95% CI 2.63-5.08), and for women with one first-degree relative with colorectal cancer diagnosed at age <50 years (HR 1.48, 95% CI 1.15-1.91).
CONCLUSION: An increased risk of endometrial cancer is associated with a family history of endometrial cancer or early-onset colorectal cancer for women without a MMR gene mutation, indicating for potential underlying genetic and environmental factors shared by colorectal and endometrial cancers other than caused by MMR gene mutations.

Related: Colorectal (Bowel) Cancer

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