Hypermethylation of E-cadherin in endometrial carcinoma

Objective

Hypermethylation of CpG island is a common mechanism for the inactivation of tumor suppressor genes. Hypermethylation of the E-cadherin promoter region has been rarely studied in endometrial carcinoma of Korean women. The purpose of this study is to investigate methylation status of E-cadherin promoter region in endometrial carcinomas and endometrial hyperplasias, and analyze the correlation with clinicopathologic variables in endometrial carcinomas.

Methods

We examined the methylation status of the E-cadherin promoter region using methylation specific polymerase chain reaction and immunohistochemical expression (IHC) of E-cadherin in 30 endometrioid endometrial carcinomas and 20 endometrial hyperplasias, and correlated these results with various clinicopathological factors of endometrial carcinomas.

Results

Decreased expression of E-cadherin was detected in 13 of 30 (43.3%) endometrial carcinomas and in 1 of 20 (5%) endometrial hyperplasias (p=0.009). Promoter hypermethylation was detected in 12 of 30 (40%) endometrial carcinomas and 2 of 20 (10%) endometrial hyperplasias (p=0.015). Methylation status did not have a significant influence on the tumor grade and lymph node metastasis. However, the hypermethylation rate was significantly higher in stage above Ic (p=0.025). Decreased expression of E-cadherin was associated with tumor grade, tumor stage, and lymph node metastasis in endometrial carcinomas (p=0.01, p=0.02, p=0.03). There was no correlation between DNA hypermethylation and decreased expression of E-cadherin in endometrial carcinomas (p>0.05).

Conclusion

These results indicate that hypermethylation of E-cadherin promoter region is a frequent event in endometrial carcinoma, which may play an important role in the progression of carcinogenesis. Also, the promoter methylation of E-cadherin in endometrial carcinoma was found to be significantly associated with higher stage above Ic.     

Serum leptin,adiponectin and endometrial cancer risk in Chinese women

Objective

To investigate the relationship between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women.

Methods

We conducted a case-control study of a total of 516 Chinese women to detect the relationships between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women. The study subject constituted 206 cases of endometrial cancer and 310 normal controls.

Results

Patients with endometrial carcinoma had higher serum leptin concentrations than controls (28.8±2.2 ug/L vs. 19.8±1.4 ug/L; p<0.001). The adiponectin levels in patients were lower than in controls with borderline statistical significance (2,330.7±180.5 ug/L vs. 2,583.9±147.2 ug/L; p=0.078). Logistic regression analysis confirmed the associations between leptin or adiponectin, and endometrial carcinoma after adjustment for age, body mass index, fasting insulin, serum glucose, cholesterol, triglycerides, and high-density lipoprotein cholesterol (odds ratio for the top tertile vs. the bottom tertile: leptin 2.05; 95% confidence interval [CI], 1.28 to 3.29; p<0.001; adiponectin 0.52; 95% CI, 0.32 to 0.83; p<0.001).

Conclusion

Increased leptin or decreased adiponectin levels are associated with endometrial carcinoma.     

Combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinoma in vitro

Objective

The aim of the study was to investigate whether lithium chloride and medroxyprogesterone acetate can potentiate the cytotoxicity of imatinib mesylate in human endometrial cancer in vitro and the effect of midkine in these therapies.

Methods

Imatinib mesylate (50 µM), lithium chloride (100 µM), medroxyprogesterone acetate (200 µM) and their combination were applied to monolayer and three dimensional cultures of human Ishikawa endometrial cancer for 72 hours. The cell proliferation index, apoptotic index, caspase-3 and midkine levels, cell cycle distributions in monolayer cultures and cell ultrastructure in spheroid cultures were evaluated. Results were statistically analyzed using the Student''s t-test.

Results

All drug applications inhibited cell proliferation (p<0.05), however the combination were the effective groups for 72 hours (p<0.05). Interestingly, although the loss of efficiency was seen higly seen every 24 hours at single applications, the inhibition rates of the combination groups were almost same for 72 hours. In concordance with these results, the apoptotic index, caspase-3 levels (p<0.05), cell morphology and ultrastructure damages were much higher in the combination groups. Imatinib mesylate induced S-phase arrest, however other groups induced G0+G1-phase arrest at 24 hours and all groups induced G0+G1 arrest at 72 hours (p<0.05). Imatinib mesylate and imatinib mesylate with medroxyprogesterone acetate induced highest decrease in midkine levels, respectively (p<0.05).

Conclusion

The present study showed that the combination of imatinib mesylate with lithium chloride and medroxyprogesterone acetate is highly active in Ishikawa endometrial carcinoma in vitro and the inhibition of midkine involved in their mechanism of action against endometrium defense.     

Laparoscopic surgery for endometrial cancer: increasing body mass index does not impact postoperative complications

Objective

To determine the effect of body mass index on postoperative complications and the performance of lymph node dissection in women undergoing laparoscopy or laparotomy for endometrial cancer.

Methods

Retrospective chart review of all patients undergoing surgery for endometrial cancer between 8/2004 and 12/2008. Complications graded and analyzed using Common Toxicity Criteria for Adverse Events ver. 4.03 classification.

Results

168 women underwent surgery: laparoscopy n=65, laparotomy n=103. Overall median body mass index 36.2 (range, 18.1 to 72.7) with similar distributions for age, body mass index and performance of lymph node dissection between groups. Following laparoscopy vs. laparotomy the percent rate of overall complications 53.8:73.8 (p=0.01), grade ≥3 complications 9.2:34.0 (p<0.01), ≥3 wound complications 3.1:22.3 (p<0.01) and ≥3 wound infection 3.1:20.4 (p=0.01) were significantly lower after laparoscopy. In a logistic model there was no effect of body mass index (≥36 and<36) on complications after laparoscopy in contrast to laparotomy. Para-aortic lymph node dissection was performed by laparoscopy 19/65 (29%): by laparotomy 34/103 (33%) p=0.61 and pelvic lymph node dissection by laparoscopy 21/65 (32.3%): by laparotomy 46/103 (44.7%) p=0.11. Logistic regression analysis revealed that for patients undergoing laparoscopy for stage I disease there was an inverse relationship between the performance of both para-aortic lymph node dissection and pelvic lymph node dissection and increasing body mass index (p=0.03 and p<0.01 respectively) in contrast to the laparotomy group where there was a trend only (p=0.09 and 0.05).

Conclusion

For patients undergoing laparoscopy, increasing body mass index did not impact postoperative complications but did influence the decision to perform lymph node dissection.     

Comparison of laparoscopic versus conventional open surgical staging procedure for endometrial cancer

Objective

The aim of this study was to compare the surgical outcomes of laparoscopic surgery and conventional laparotomy for endometrial cancer.

Methods

A total of 104 consecutive patients were non-randomly assigned to either laparoscopic surgery or laparotomy. All patients underwent comprehensive surgical staging procedures including total hysterectomy, bilateral salpingo-oophorectomy, and pelvic/para-aortic lymphadenectomy. The safety, morbidity, and survival rates of the two groups were compared, and the data was retrospectively analyzed.

Results

Thirty-four patients received laparoscopic surgery and 70 underwent laparotomy. Operation time for the laparoscopic procedure was 227.0±28.8 minutes, which showed significant difference from the 208.1±46.4 minutes (p=0.032) of the laparotomy group. The estimated blood loss of patients undergoing laparoscopic surgery was 230.3±92.4 mL. This was significantly less than that of the laparotomy group (301.9±156.3 mL, p=0.015). The laparoscopic group had an average of 20.8 pelvic and 9.1 para-aortic nodes retrieved, as compared to 17.2 pelvic and 8.5 para-aortic nodes retrieved in the laparotomy group. There was no significant difference (p=0.062, p=0.554). The mean hospitalization duration was significantly greater in the laparotomy group than the laparoscopic group (23.3 and 16.4 days, p<0.001). The incidence of postoperative complications was 15.7% and 11.8% in the laparotomy and laparoscopic groups respectively. No statistically significant difference was found between the two groups in the survival rate.

Conclusion

Laparoscopic surgical staging operation is a safe and effective therapeutic procedure for management of endometrial cancer with an acceptable morbidity compared to the laparotomic approach, and is characterized by far less blood loss and shorter postoperative hospitalization.     

Relevance of Bcl-x expression in different types of endometrial tissues

Objectives

To explore the roles of Bcl-xl and Bcl-xs in the development and progression of endometrial carcinoma, and to analyze the correlation between Bcl-xl and Bcl-xs.

Methods

RT-PCR and Western-blot assay were applied to detect the expressions of Bcl-xl and Bcl-xs in endometrial tissues of various histomorphologic types.

Results

The Bcl-xl expression levels of simple and atypical hyperplasia endometrial tissues were not significantly different from that of normal endometrial tissue (both P > 0.05). On contrary, Bcl-xl expression in endometrial carcinoma tissue was significantly higher than the normal endometrial tissue (P = 0.00), which was correlated with the pathological grading of endometrial carcinoma (F = 5.33, P = 0.02). In addition, Bcl-xs mRNA level in simple hyperplasia endometrial tissue had no significant difference compared to that in normal endometrial tissue (P = 0.12), while the levels of atypical hyperplasia and endometrial carcinoma endometrial tissues were significantly different from the normal endometrial tissue (both P = 0.00). Furthermore, level of Bcl-xs mRNA was correlated with the clinical staging and lymph node metastasis of the endometrial carcinoma (P < 0.05). The expressions of Bcl-xl and Bcl-xs were negatively correlated with each other (r = -0.76).

Conclusion

The abnormal expressions of Bcl-xs and Bcl-xl were one of the molecular mechanisms for the pathogenesis of endometrial carcinoma, and altered ratio between these two might involve in the onset of endometrial carcinoma.     

Risk factor analysis of coexisting endometrial carcinoma in patients with endometrial hyperplasia: a retrospective observational study of Taiwanese Gynecologic Oncology Group

Objective

To evaluate the clinical outcome and parameters related to coexisting endometrial carcinoma in women with tissue-diagnosed endometrial hyperplasia.

Methods

Between January 1991 and December 2009, three hundred and eighty-six patients with the presumptive diagnosis of endometrial hyperplasia were retrieved. Among these, one hundred and twenty-five patients were identified as having coexisting endometrial carcinoma in hysterectomy specimens. The three hundred and eighty-six patients were divided into two groups: the hyperplasia-benign group (261 cases) and the hyperplasia-malignant group (125 cases). Several clinical parameters including age, menopausal status, history of abnormal uterine bleeding, obstetrical history, medical history of diabetes and hypertension, BMI, and preoperative pathologic results were investigated.

Results

Age ≥53 (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.26 to 4.57), menopausal status (OR, 2.07; 95% CI, 1.14 to 3.76), diabetes history (OR, 7.33; 95% CI, 2.79 to 19.26), abnormal uterine bleeding (OR, 3.99; 95% CI, 1.22 to 13.02), atypical endometrial hyperplasia (OR, 7.38; 95% CI, 4.03 to 13.49), and body mass index ≥27 (OR, 3.24; 95% CI, 1.76 to 5.97) were independent risk factors for prediction of endometrial hyperplasia coexisting with endometrial carcinoma. The diagnostic efficacy of atypical endometrial hyperplasia to predict the endometrial hyperplasia coexisting with endometrial carcinoma was better than or similar to those of other independent factors and combinations of these factors.

Conclusion

Coexisting malignancy should be considered when examining endometrial hyperplasia patients with the related risk factors, especially atypical endometrial hyperplasia.     

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

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.     

Synchronous and metachronous malignancy in endometrial cancer patients treated in a tertiary care center of Thailand

Objective

To evaluate the prevalence and features of non-endometrial cancers in Thai endometrial cancer (EC) patients.

Methods

EC patients treated in our institution were identified and the following data were collected: age, EC stage, histopathology, adjuvant therapy, other cancers, living status, and cause of death.

Results

The mean age of the 344 patients was 56.8±10.8 years. Fifty (14.5%) had other synchronous and metachronous cancers. Mean ages of the patients with or without other cancers were not significantly different, 55.7±10.04 years versus 57.1±11.0 years, respectively (p=0.358). History of any cancer in the family and tumor in the lower uterine segment were more frequent among the patients with other cancers (6.0% vs. 1.7%, p=0.095; 12.0% vs. 1.0%, p<0.001; respectively). Six patients had ≥2 other cancers. Ovarian, breast, and colon were the three most common other cancers. After a median follow-up of 57.1 months, 18.3% of patients had died: 30.0% of patients with other cancers and 16.3% of those without other cancers. The corresponding EC deaths were 14.0% and 11.2%. The 5-year overall survival was significantly lower in patients who had other cancers: 79.3% (95% confidence interval [CI], 68.3 to 90.3) vs. 86.0% (95% CI, 81.7 to 90.3) than in those without (p=0.023). However, the corresponding disease-specific survival was not significantly different: 85.1% (95% CI, 75.5 to 94.7) compared with 89.0% (95% CI, 85.1 to 92.9), respectively (p=0.514).

Conclusion

Thai EC patients had a high incidence of other cancers. Overall survival of EC patients who had other cancers was worse than those without, while disease-specific survival was not significantly different.     

Syndecan-1, a key regulator of cell viability in endometrial cancer

Syndecan-1 is one of the major proteoglycans on cell surfaces involved in major biological processes. Although loss of syndecan-1 correlates well with the gain of cancerous characteristics in a wide range of cancers, increased expression of syndecan-1 also coincides with adverse outcomes in some cancers, including breast, ovarian and pancreatic cancers. For this Janus-faced attitude of syndecan-1, we sought to examine expression patterns of syndecan-1 in endometrial carcinoma (EC) and gain insight into the roles of syndecan-1. Immunohistochemical examinations of 109 endometrial tissue samples from myoma, hyperplasia and EC uteri revealed that syndecan-1 expression was significantly upregulated in EC compared with hyperplasia (p < 0.001). To evaluate pathophysiological functions of syndecan-1, its expression level was altered, and subsequent outcomes were examined using human endometrial cancer cell lines such as HEC-1A, AN3CA and KLE cells. Overexpression of syndecan-1 increased the growth of HEC-1A cells regardless of anchorage dependence while silencing syndecan-1 by antisense RNAs caused apoptotic cell death. Consistent with decreased viability, the loss of syndecan-1 was also accompanied by a decrease in the activation of Erk and Akt and a concomitant decrease in the phosphorylation of PTEN and PDK1, which are known as negative and positive regulators of Akt activation, respectively. These down-regulatory effects were reversed upon overexpression of syndecan-1. Collectively together, the aforementioned findings lend support to the notion that upregulation of syndecan-1 may be a critical element for endometrial cancers in maintaining their viability and thus can serve as a cancer specific therapeutic and diagnostic marker.     

Expression and clinical significance of annexin A2 and human epididymis protein 4 in endometrial carcinoma

Background

It is well-known that the treatment and monitoring methods are limited for advanced stage of endometrial carcinoma. Biological molecules with expression changes during tumor progression become potential therapeutic targets for advanced stage endometrial carcinoma. Annexin A2 (ANXA2) has been reported to be overexpressed in recurrent endometrial carcinoma, and the expression of human epididymis protein 4 (HE4) is upregulated in endometrial carcinoma. What’s more, ANXA2 and HE4 interacted in ovarian cancer and promoted the malignant biological behavior. We speculated that their interaction may exist in endometrial carcinoma as well. We evaluated the expression and the correlation relationship of ANXA2 and HE4 in endometrial carcinoma.

Methods

The expression of ANXA2 and HE4 protein in 84 endometrial carcinoma, 30 endometrial atypical hyperplasia, and 18 normal endometrial tissue samples were then measured using an immunohistochemical assay in paraffin embedded endometrial tissues. The structural relationship between ANXA2 and HE4 was explored by immunoprecipitation and double immunofluorescent staining.

Results

ANXA2 and HE4 co-localized in both endometrial tissues and endometrial carcinoma cells. ANXA2 and HE4 were expressed in 95.2 % and 85.7 % of the the endometrial carcinoma, respectively, which were significantly higher than normal endometrium (55.6 % and 16.7 %, both p < 0.05). The expression of ANXA2 and HE4 was significantly correlated with FIGO stage, degree of differentiation, myometrial invasion, and lymph node metastasis. ANXA2 was an independent risk factor for the prognosis of endometrial carcinoma (p < 0.05, hazard ratio [HR] = 8.004). The expression of ANXA2 and HE4 was positively correlated (Spearman correlation coefficient = 0.228, p < 0.05). HE4 was an independent factor for ANXA2 in multivariate linear regression model (p < 0.05).

Conclusion

We revealed the co-localization of ANXA2 and HE4 in endometrial carcinoma. Expression levels of ANXA2 and HE4 were closely related to the malignant biological behavior of endometrial carcinoma, and ANXA2 was an independent risk factor for poor prognosis. The expression of ANXA2 and HE4 can affect each other.

Electronic supplementary material

The online version of this article (doi:10.1186/s13046-015-0208-8) contains supplementary material, which is available to authorized users.     

Clinicopathological characteristics,treatment and outcomes in uterine carcinosarcoma and grade 3 endometrial cancer patients: a comparative study

Objective

Uterine carcinosarcoma (UCS) shared the same staging system with endometrial carcinoma in the International Federation of Gynecology and Obstetrics 2009. The aim of the present study was to compare the clinicopathological and prognostic characteristics between UCS and grade 3 endometrioid endometrial carcinoma (G3EC).

Methods

A retrospective analysis of 60 UCS and 115 G3EC patients with initial treatment at the Department of Gynecology in the Fudan University Shanghai Cancer Center between February 2006 and August 2013. Chi-square analysis was used to compare differences between variables. Prognostic factors were determined using univariate/multivariate analysis, and the survival rates were assessed using the Kaplan-Meier method. The Cox regression model was used to assess the independent prognostic factor.

Results

UCS had significantly worse overall survival (OS) compared with G3EC. Carcinosarcoma subtype was an independent factor (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.0 to 5.8; p=0.039), stratified based on stage. Compared with G3EC, UCS patients had a greater incidence of ascites fluid (55.0% vs. 15.7%, p<0.001) and adnexal involvement (20.0% vs. 8.7%, p=0.048) and larger median tumor volume (4.6 cm vs. 4.0 cm, p=0.046). Subgroup analysis of the prognostic factors revealed that UCS patients exhibited worse OS than G3EC patients in such specific subgroups as patients at younger ages, with postmenopausal status, without ascites fluid, with early stage diseases, without vagina invasion, without lymph node metastases and receiving adjuvant chemo/radiotherapy. Adjuvant radiotherapy with chemotherapy was predictive of better survival in UCS patients compared with chemotherapy or radiotherapy alone (5-year OS, 71.0% vs. 35.8%, p=0.028). Multivariate Cox regression revealed that tumor mesenchymal component (HR, 4.6; 95% CI, 1.4 to 15.8; p=0.014) was an independent prognostic factor for UCS, whereas advanced stages (HR, 5.9; 95% CI, 1.0 to 33.9; p=0.046) and ascites fluid (HR, 5.1; 95% CI, 1.1 to 22.7; p=0.032) were independently correlated with poor prognosis for G3EC patients.

Conclusion

The distinctions in both clinicopathological and prognostic characteristics between UCS and G3EC suggest that this subtype should be treated separately from high-risk epithelial endometrial carcinoma.     

子宫内膜癌中p16基因甲基化与表达的研究

目的 研究ｐ１６基因甲基化状态及其ｐ１６基因表达异常与子宫内膜癌发生发展的关系。方法 采用限制性内切酶酶切、ＰＣＲ及ＲＴ－ＰＣＲ检测子宫内膜检测ｐ１６基因５’ＣｐＧ岛甲基化状态及ｐ１６基因ｍＲＮＡ表达。结果 ８例正常子宫内膜无甲基化,且ｐ１６ ｍＲＮＡ表达正常。６例子宫内膜非典型增生中,有１例甲基化;３８例子宫内膜癌中,１３例甲基化,占３４．２％。６例子宫内膜单纯及复合增生中,有５例ｐ１６ ｍＲＮ     

Risk factors for recurrence amongst high intermediate risk patients with endometrioid adenocarcinoma

Objective

To determine risk factors associated with recurrence in patients with high intermediate risk (HIR) endometrioid adenocarcinoma.

Methods

A retrospective analysis of patients with HIR endometrioid adenocarcinoma who underwent hysterectomy, bilateral salpingo-oophorectomy, with or without pelvic/para-aortic lymphadenectomy at the University of Pennsylvania between 1990 and 2009 was performed.

Results

A total of 103 women with HIR endometrial cancer were identified. Multivariable analysis revealed that ≥2/3 myometrial invasion (HR, 4.79; p=0.010) and grade 3 disease (HR, 3.04; p=0.045) were independently predictive of distant metastases. The 5-year distant metastases free survival (DMFS) for patients with neither or one of these risk factors was 89%, and the 5-year DMFS for patients with both risk factors was 48% (p<0.001).

Conclusion

Patients with both grade 3 disease and deep third myometrial invasion have a high risk of distant metastases. Identifying these patients may be important in rationally selecting patients for systemic therapy.     

Prognostic significance of syndecan-1 expression in cervical cancers

Objective

Syndecans are reported to have variable expression in several solid tumors and blood cancers. The cause provoking altered expression of syndecans is not known to date. We studied copy number status of syndecan-1 (SDC1) and significance of SDC1 gene product (syndecan-1, SDC1) expression in cervical cancers.

Methods

Using 121 cases of cervical cancer tissues, we screened SDC1 expression pattern using immunohistochemistry. We analyzed the relationship between SDC1 expression and clinicopathological parameters. To find possible causes of the expression change, we exploited interphase fluorescent in situ hybridization to screen copy number alteration of SDC1.

Results

Among 121 cases, 101 (83.5%) were positive and 20 (16.4%) were negative for SDC1. Among the parameters, age, histological type, and grade were significantly associated with SDC1 expression (p<0.05). Strong SDC1 expression in the cytoplasm showed better patient survival (p=0.02). In multivariate regression model, grade and SDC1 expression were independent prognostic factors (p<0.05). SDC1 in cervical cancers did not show copy number alteration.

Conclusion

Strong SDC1 expression in the cytoplasm of tumor cells predicts better patient survival. The change of SDC1 expression in cervical cancers is not caused by copy number alteration of the gene.     

Physical activity for an ethnically diverse sample of endometrial cancer survivors: a needs assessment and pilot intervention

Objective

To determine the physical activity (PA) behavior, needs and preferences for underserved, ethnically diverse women with a history of endometrial cancer (EC).

Methods

Women with a history of EC (41 non-Hispanic black, 40 non-Hispanic white, and 18 Hispanic) completed a needs assessment during their regular follow-up appointments at Montefiore Medical Center in Bronx, NY, USA. An 8-week pilot PA intervention based on the results of the needs assessment was conducted with 5 EC survivors.

Results

Mean body mass index (BMI) among the 99 respondents was 34.1±7.6 kg/m², and 66% did not exercise regularly. Self-described weight status was significantly lower than actual BMI category (p<0.001). Of the 86% who were interested in joining an exercise program, 95% were willing to attend at least once weekly. The primary motivations were improving health, losing weight, and feeling better physically. Despite the high interest in participation, volunteer rate was very low (8%). However, adherence to the 8-week pilot PA intervention was high (83%), and there were no adverse events. Body weight decreased in all pilot participants.

Conclusion

These data show that ethnically diverse EC survivors have a great need for, and are highly interested in, PA interventions. However, greater care needs to be taken to assess and identify barriers to increase participation in such programs.     

The effectiveness of levonorgestrel releasing intrauterine system in the treatment of endometrial hyperplasia in Korean women

Objective

Levonorgestrel releasing intrauterine system (LNG-IUS) has been shown to treat patients with non-atypical & atypical endometrial hyperplasia (EH) successfully in many western studies. Our purpose was to examine the effectiveness of LNG-IUS in the treatment of Korean women with EH.

Methods

We conducted a prospective observational study of 12 women diagnosed with EH and treated with LNG-IUS insertion between February 2007 and August 2009 at the Department of Gynecology of Gangnam CHA Hospital, CHA University School of Medicine. Baseline endometrial biopsies were done before insertion of LNG-IUS, and outpatient follow-up endometrial biopsies were undertaken at 3-month intervals after insertion of LNG-IUS. We investigated the regression rate and the time to regression.

Results

Four patients had simple hyperplasia without atypia, 7 patients complex hyperplasia without atypia, and just 1 patient complex atypical hyperplasia. Complete regression of EH was achieved in all cases (100%, 12/12), with the significant proportion (66%, 8/12) achieving it within 3 months. The mean duration to regression was 4.5 months. All cases had regression within 9 months. In the case of complex atypical hyperplasia, the regression was attained at the 9th month after insertion of LNG-IUS. The mean follow-up duration was 12 months (range, 3 to 27 months). As long as LNG-IUS was maintained, the EH did not recur.

Conclusion

LNG-IUS appears to be as highly effective in treating Korean women with EH.     

Androgen receptors are acquired by healthy postmenopausal endometrial epithelium and their subsequent loss in endometrial cancer is associated with poor survival

Background:

Endometrial cancer (EC) is a hormone-driven disease, and androgen receptor (AR) expression in high-grade EC (HGEC) and metastatic EC has not yet been described.

Methods:

The expression pattern and prognostic value of AR in relation to oestrogen (ERα and ERβ) and progesterone (PR) receptors, and the proliferation marker Ki67 in all EC subtypes (n=85) were compared with that of healthy and hyperplastic endometrium, using immunohistochemisty and qPCR.

Results:

Compared with proliferative endometrium, postmenopausal endometrtial epithelium showed significantly higher expression of AR (P<0.001) and ERα (P=0.035), which persisted in hyperplastic epithelium and in low-grade EC (LGEC). High-grade EC showed a significant loss of AR (P<0.0001), PR (P<0.0001) and ERβ (P<0.035) compared with LGEC, whilst maintaining weak to moderate ERα. Unlike PR, AR expression in metastatic lesions was significantly (P=0.039) higher than that in primary tumours. Androgen receptor expression correlated with favourable clinicopathological features and a lower proliferation index. Loss of AR, with/without the loss of PR was associated with a significantly lower disease-free survival (P<0.0001, P<0.0001, respectively).

Conclusions:

Postmenopausal endometrial epithelium acquires AR whilst preserving other steroid hormone receptors. Loss of AR, PR with retention of ERα and ERβ may promote the unrestrained growth of HGEC. Androgen receptor may therefore be a clinically relevant prognostic indicator and a potential therapeutic target in EC.     

Risk group criteria for tailoring adjuvant treatment in patients with endometrial cancer: a validation study of the Gynecologic Oncology Group criteria

Objective

The purpose of this study is to validate the Gynecologic Oncology Group (GOG) criteria for adjuvant treatment in a different cohort of patients and to evaluate the simplified risk criteria predicting the prognosis and tailoring adjuvant treatment in patients with surgically staged endometrial cancer.

Methods

We performed a retrospective analysis of 261 consecutive patients with surgically staged endometrial cancer between January 2000 and February 2013. All patients had complete staging procedures and were surgically staged according to the 2009 International Federation of Gynecology and Obstetrics staging system. Clinical and pathologic data were obtained from medical records. We designed the simplified risk criteria for adjuvant treatment according to the risk factors associated with survival. The patients were divided into low and low-intermediate, high-intermediate, and high-risk groups according to the GOG criteria and simplified criteria and their survivals were compared. Receiver-operating characteristic curve analysis was used to evaluate the prognostic significance of both criteria.

Results

Median follow-up time was 48 months (range, 10 to 122 months). According to the GOG criteria, we identified 197 low and low-intermediate risk patients, 20 high-intermediate risk patients, and 44 high-risk patients. There were significant differences in disease-free (p<0.001) and overall survival (p<0.001) among the three groups. Using the simplified risk criteria, we identified 189 low and low-intermediate risk patients, 28 high-intermediate risk patients, and 44 high-risk patients. There were significant differences in disease-free (p<0.001) and overall survival (p<0.001) among the three groups. The performance of the simplified criteria (area under the curve [AUC]=0.829 and 0.916 for disease recurrences and deaths, respectively) was as good as the GOG criteria (AUC=0.836 and 0.921 for disease recurrences and deaths, respectively).

Conclusion

The simplified criteria may be easily applicable and offer useful information for planning strategy of adjuvant treatment in patients with surgically staged endometrial cancer as the GOG criteria.