Bilateral ovarian fibromas and endometrial adenocarcinoma in a postmenopausal patient with growing uterine myomas

Bilateral ovarian fibromas are a rare condition. We report a case of bilateral ovarian fibromas with endometrial adenocarcinoma in a postmenopausal woman who clinically showed symptoms of an estrogen-producing tumour. Clinical and histopathological problems in the pre- and intraoperative diagnostics of fibromas are discussed.     

Galectin-3在子宫内膜息肉中的表达及意义

目的 探讨子宫内膜息肉中Galectin-3的表达及Galectin-3与子宫内膜息肉发生的关系.方法 用免疫组织化学法检测Galectin-3在绝经前后子宫内膜息肉及正常子宫内膜中的表达.其中绝经前子宫内膜息肉51例,正常子宫内膜40例;绝经后子宫内膜息肉40例,正常内膜38例.结果 ①Galectin-3在绝经前子宫内膜息肉及正常内膜中均有表达,绝经前子宫内膜息肉中的表达高于正常内膜,差异有统计学意义(x2=37.640,P＜0.01).②Galectin-3在绝经后子宫内膜息肉及正常内膜中均有表达,绝经后内膜息肉中的表达高于正常内膜,差异有统计学意义(x2=30.664,P＜0.01).③Galectin3在绝经前、后内膜息肉中的表达差异无统计学意义(x2=1.894,P＞0.05).结论 ①Galectin-3在绝经前后内膜息肉中的高表达,提示Galectin-3可能与子宫内膜息肉的发生有关.②Galectin-3在绝经前后内膜息肉中的表达差异无统计学意义,表明绝经后内膜息肉更易恶变可能与Galectin-3无关.     

Transvaginal ultrasonography for identifying endometrial pathology in postmenopausal women

The objective of this study was to evaluate the usefulness of transvaginal ultrasonography in postmenopausal women with a clinical indication for a dilatation and curettage (D&C). Of the 167 postmenopausal women included in the study, 88% were referred for a D&C because of vaginal bleeding and 12% of the women had other clinical indications such as myomas, gynecological pain or suspected gynecological tumors. Hormone replacement therapy (HRT) was used by 37% of the women. The women were examined with transvaginal ultrasonography before the D&C. The endometrial thickness and texture were used as indicators of endometrial abnormalities. The ultrasonographical findings were related to the histological diagnosis obtained from the D&C. Histologically, 31% of the women had an atrophic endometrium and the corresponding ultrasonographically mean endometrial thickness was 4.6 mm (range 0–14 mm). Endometrial cancer was histologically found in 10% of the women and the endometrial thickness of the malignant endometrium, measured by ultrasonography, was 13.9 mm (range 6–31 mm). All the malignancies were found in the group of women with vaginal bleeding, but only one was in the group of women on HRT. Histologically, endometrial hyperplasia was found in 6.5% of the women and endometrial polyps in 8.5% after the D&Cs. In these postmenopausal women it was demonstrated that if the endometrium was < 6 mm thick, no endometrial cancer was found at histopathological investigation. By using a cut-off point of 6 mm of ultrasonographically measured endometrial thickness for identification of endometrial pathology in our study, at least 50% of the D&Cs could be spared.     

Hysterography in evaluating the uterine cavity in patients with endometrial carcinoma

In 49 patients with endometrial carcinoma hysterographic study was performed. This finding was correlated with fractional curettage, hysteroscopy and surgery. The best correlation was noted between hysterography and hysteroscopy. The flow into the tubes or abdominal cavity using low pressure was found in 20% of the cases. In our opinion hysterography is a useful aid when examining the uterine cavity and cervical canal, and, thus, important when planning treatment and determining clinical stage.     

Comparison of forearm endothelial function between premenopausal and postmenopausal women with or without hypercholesterolemia

We sought to determine whether menopausal status or postmenopausal hypercholesterolemia affects forearm resistance artery endothelial function. We studied the forearm resistance artery endothelial function in 75 Japanese women: 25 premenopausal volunteers, 25 postmenopausal women with normal serum low-density lipoprotein (LDL) cholesterol concentrations, and 25 hypercholesterolemic postmenopausal women. Excluded from the study were patients with hypertriglyceridemia, hypertension, or diabetes, cigarette smokers. The forearm blood flow (FBF) during reactive hyperemia and after sublingual nitroglycerin (NTG) administration was measured by strain-gauge plethysmography. The serum concentrations of lipoprotein (a) [Lp(a)] were significantly higher in the hypercholesterolemic postmenopausal group than in the other two groups (P<0.01). These lipid parameters were similar between the premenopausal and postmenopausal women with normal cholesterol. The FBF responses to reactive hyperemia were significantly lower in the postmenopausal hypercholesterolemic women than in the other two groups (P<0.01). The reactive hyperemia also was impaired in the postmenopausal group with normal cholesterol as compared with the premenopausal group (P<0.01). Increases in FBF after NTG were similar between the three groups. By stepwise multivariate analysis, menopausal status and serum LDL cholesterol was the significant predictor of forearm endothelial function. These findings suggest that reactive hyperemia is impaired in forearm resistance arteries after menopause, especially in postmenopausal women with hypercholesterolemia.     

Ag-NOR protein distribution correlates with patient survival in stage I endometrial adenocarcinoma

Summary The relationship between argyrophil nucleolar organizer region (Ag-NOR) protein quantity and prognosis was studied in 33 cases of stage I endometrial adenocarcinoma. Ag-NOR protein quantity was measured by image analysis in silver-stained sections from paraffin-embedded samples of curettings. Patients had a minimum 10-year follow-up. Only 2 out of 25 patients exhibiting a mean Ag-NOR protein area of less than 3 m² died of cancer, whereas 5 of the 8 patients with a mean Ag-NOR protein area of more than 3 m² died of the disease. The present results demonstrate that the Ag-NOR protein value is closely related to patient survival in stage I endometrial carcinoma and that it is a reliable prognostic indicator in this type of carcinoma.     

Testosterone and 17β-oestradiol secretion of the human ovary. II. Normal postmenopausal women,postmenopausal women with endometrial hyperplasia and postmenopausal women with adenocarcinoma of the endometrium

A study of the concentration of testosterone and of 17β-estradiol in blood drawn from the ovarian and cubital veins of normal oestrogen-deficient postmenopausal women and of postmenopausal women with signs of oestrogen activity, and the subsequent computation of the ovarian production rates of these two hormones, show that in the latter group of women there is a high ovarian secretion of testosterone. The theory is advanced that this ovarian-secreted testosterone is rapidly converted into 17β-oestradiol, and that, by thus increasing the levels of circulating oestrogens, ovarian-secreted testosterone contributes, albeit indirectly, to endometrial hyperplasia and possibly to endometrial carcinoma.     

Expression of poly-ADP-ribose polymerase (PARP) in endometrial adenocarcinoma: Prognostic potential

BackgroundIn the United States endometrial carcinoma is the most common female gynecologic malignancy. An average of more than 60,000 new cases of endometrial carcinomas have been diagnosed yearly over the past 5 years, with a higher incidence occurring in the central Appalachian states of Ohio and West Virginia. In the U.S., the national average of newly diagnosed endometrial carcinomas is 26.8 in every 100,000 women, while in the states of Ohio and West Virginia the average is 30.5 and 31.1 in every 100,000 women, respectively. This notable increase in the incidence of endometrial carcinomas may be due a variety of elevated risk factors including but not limited to: tobacco use, obesity, and genetic predisposition of the predominant demographic. The American Cancer Society estimates that approximately 55,000 new cases of endometrial carcinoma will be diagnosed in 2020 yet, this disease is widely considered understudied and under-represented in mainstream cancer research circles.MethodsThe aim of this study was to quantitate the co-expression of two DNA repair proteins poly-ADP-ribose polymerase 1 and 2 (Parp-1 and Parp-2) by enzyme- linked immuno-sorbent assay (ELISA) in 60 endometrioid endometrial tumor samples and compare their expression to matched non-malignant endometrial tissue from the same corresponding donors from central Appalachia.ResultsWe found that Parp-1 was significantly overexpressed in endometrial carcinoma relative to corresponding normal tissue. This overexpression implicates Parp inhibition therapy as a possible treatment for the disease. Our results also found a protective effect of native Parp-2 expression in non-malignant endometrial tissue with each 1 ng/mL increase in PARP-2 concentration in normal tissue was associated with a 10 % reduction in the hazard of tumor progression (HR = 0.90; p = 0.039) and a 21 % reduction in the hazard of death (HR = 0.79; p = 0.044).ConclusionsThis study demonstrated the over-expression of the druggable target Parp-1 in endometrial adenocarcinoma and observed a strong negative correlation of native Parp-2 expression and disease progression via the quantification of the Parp proteins using enzyme- linked immuno-sorbent assay (ELISA) assays.     

PTEN mutation: A potential prognostic factor associated with immune infiltration in endometrial carcinoma

BackgroundEndometrial carcinoma (EC) is a genetic disease, normally accompanied by gene mutations or abnormal expression patterns. However, PTEN mutation and its prognostic value in EC remained debated. Meanwhile, the distribution of PTEN mutation, as well as its correlation with clinical characteristics and tumor immune infiltrating cells, is still poorly understood.MethodsWe conducted a comprehensive analysis of PTEN mutation based on The Cancer Genome Atlas (TCGA) database, including 525 uterine corpus endometrial carcinoma (UCEC) samples. We analyzed the frequency of PTEN mutation, distribution of PTEN mutation in different clinical characteristics, the prognostic value of PTEN mutation, and the correlation with tumor immune infiltrating cells in tumor microenvironment.ResultsPTEN mutation was detected in 65.5﹪of total EC samples. PTEN mutation was significantly associated with age, histological type, clinical stage, and grade. In addition, the patients with PTEN mutation showed a significantly prolonged overall survival (OS) time and disease free survival (DFS) time compared with EC patients without PTEN mutation in entire group, training group, and validation group. Multivariate Cox regression analyses suggested that PTEN mutation was an independent prognostic factor in DFS. Moreover, the percentages of Tregs (P = 0.014) and M1 macrophages (P = 0.013) were significantly different in PTEN mutation group and non-mutation group.ConclusionPTEN mutation was correlated with favorable prognosis in EC patients. In addition, PTEN mutation was found to be associated with immune infiltrating cells in tumor microenvironment. Taken together, these findings suggested that PTEN could be regarded a potential predictive and therapeutic target for EC.     

子宫内膜癌组织中cyclin E和p27表达的相关性及其与临床预后的关系

目的 :探讨子宫内膜癌组织中cyclinE与 p2 7表达的相关性及其与临床预后的关系。方法 :用免疫组化方法检测 40例子宫内膜癌、10例子宫内膜不典型增生、2 0例正常子宫内膜组织中cyclinE和p2 7的表达 ,并用Log Rank检验p2 7蛋白和cyclinE蛋白表达与子宫内膜癌患者生存率的关系。结果 :cyclinE表达的阳性率 ,子宫内膜癌组显著高于内膜不典型增生组和正常子宫内膜组 (P <0 .0 5 )。p2 7表达与子宫内膜癌的组织学分级、手术分期及肌层浸润深度有关 (P <0 .0 5 )。cyclinE与p2 7的表达呈负相关。cyclinE蛋白表达阳性患者生存率低于阴性患者 ,p2 7蛋白表达阳性患者生存率高于阴性患者 ,但无统计学意义 (P >0 .0 5 )。结论 :cyclinE对子宫内膜癌的发生可能起一定作用 ,p2 7则与抑制子宫内膜癌的进展有关 ,并可能成为判断预后的有用指标     

Ultrasonographic endometrial monitoring during continuous-sequential hormonal replacement therapy regimen in postmenopausal women

Objective: To evaluate the endometrial thickness in different periods of a continuous–sequential HRT regimen and to correlate the ultrasonographic findings with the histological patterns. Methods: The study was structured in two phases. In the 1st phase, 37 postmenopausal women (group A) treated by at least 6 months with a conventional continuous–sequential hormonal replacement therapy (cs–HRT) regimen were enrolled. In all patients, the endometrial thickness was measured at the 7th, 14th, 21st and 25th day of the cycle using transvaginal ultrasonography (TV-USG). In the 2nd phase of the study, other 41 postmenopausal women (group B) were enrolled and treated with the same sc-HRT regimen. At entry and after six cycles of cs–HRT, an endometrial biopsy was performed. The endometrial pattern was related with endometrial thickness. Either the evaluations were performed immediately after progestogen withdrawal bleeding, as showed by 1st phase results. Results: The results of the 1st phase of the study showed a mean endometrial thickness significantly lower at 7th day of the cycle compared to 14th, 21st and 25th day (4.3±1.2 versus 6.6±2.9, 7.8±4.2 and 7.4±4.6 mm±SD, respectively). After six cycles of cs–HRT (2nd phase of the study), the mean endometrial thickness was significantly increased in comparison with basal values (4.2±1.5 versus 2.8±1.2 mm±SD; P<0.05). Endometrial biopsies showed 13 cases (39.4%) of atrophy and 20 cases (60.6%) of proliferative endometrium. Mean endometrial thickness in case of atrophy was lower than in presence of a proliferative endometrium (3.7±1.2 versus 4.4±1.4 mm±SD; not significant). Endometrial thickness was <4 mm in 16 cases (11 of atrophic and five of proliferative endometrium), between 4 and 5 mm in 15 cases (13 of proliferative and two of atrophic endometrium) and between 5 and 6 mm in two cases (either case of proliferative endometrium). Conclusions: The best timing for monitoring endometrial thickness during cs–HRT regimens is the period immediately after withdrawal bleeding improving the reliability of the ultrasonographic exam to identify endometrial pathologies.     

Clinical usefulness of endometrial screening by ultrasound in asymptomatic postmenopausal women

Objective: The aim of the present study was to evaluate the clinical usefulness of routine use of endometrial ultrasound in asymptomatic, bleeding-free postmenopausal women. Methods: We retrospectively reviewed the data of 850 postmenopausal women subjected to hysteroscopy, focusing our attention on those cases (148) with an ultrasound indication of endometrial thickening. Results: In 850 postmenopausal women, we identified 27 (3.2%) endometrial adenocarcinomas. In these subjects, the indication for office hysteroscopy was abnormal uterine bleeding in 24 (24/27; 88.9%) cases; pathological pap smear with abnormal endometrial cells in 2 (2/27; 7.4%) cases and thickened endometrium upon transvaginal ultrasound (tvUS) only in one (1/27; 3.7%) patient. On the other hand, 148 hysteroscopies were performed on the basis of the tvUS indication in otherwise asymptomatic (bleeding free) postmenopausal women; only 1(0.7%) of these presented an adenocarcinoma. Conclusion: Our findings show that the use of tvUS as a screening tool for endometrial pathology in asymptomatic postmenopausal women generates 93.2% false positive results, so that most of these women undergo this second level invasive procedure uselessly. Our data suggest that, in asymptomatic postmenopausal women, endometrial ultrasound evaluation is not worthwhile as a screening tool, such as it is considered in common clinical practice. The present results call for a larger prospective trial to further elucidate this controversial issue.     

Hysteroscopic findings in postmenopausal abnormal uterine bleeding: a comparison between HRT users and non-users

Objectives: The aim of our study was to investigate hysteroscopic findings in a sample of 410 menopausal women (hormonal replacement therapy, HRT users n=219 and HRT non-users n=191) and to evaluate the relationship between the presence of intrauterine disease, the use of HRT and the presence of AUB. Methods: Two hundred and nineteen women on HRT underwent standard office hysteroscopy by means of the Hamou hysteroscope (in 94 cases for abnormal uterine bleeding (AUB) and in 125 cases for periodic endometrium monitoring). One hundred and ninety-one women who had never received HRT were submitted to office hysteroscopy (154 for AUB and 37 for other reasons). Results: Intrauterine diseases are more frequent in patients who do not use HRT (P=0.02). Endometrial polyps is a frequent disease present in 30% of the sample (23.7% of HRT users and 30.8% of HRT non-users). Myomas were present in 8.7% of all patients examined (6.8% of HRT users and 11% of HRT non-users). Irregular bleeding in menopause is often associated with endouterine abnormalities: in symptomatic patients the frequency of endouterine diseases was 41% while in asymptomatic patients was 28% (P=0.003). In patients taking HRT (n=219) endouterine disease is demonstrated in 37% with AUB and in 26% without AUB (P=0.07). Conclusion: Benign intrauterine diseases (endometrial polyps and submucous myomas) are more frequent in postmenopausal women who do not use HRT. In patients taking HRT irregular bleeding is associated with intrauterine diseases; however, the absence of AUB does not exclude the presence of endometrial polyps or myomas.     

Estrogen treatment of postmenopausal vaginal atrophy--a cytological assessment

The following is an assessment of the maturation value (MV) based upon cytohormonal smears of postmenopausal or hysterectomized patients: (1) There is a negative correlation between the MV and the number of postmenopausal years. (2) There is a positive correlation between MV values higher than 60 and urinary excretion of estrogens. (3) The MV is ideally suited to demonstrate the beneficial effect of various estrogens on the vaginal mucosa. (4) Though its action is delayed, and necessitates a threshold dose of 33 micrograms/kg weight/wk, estriol might be considered as the drug of choice for a beneficial effect on the vaginal mucosa, because of its lack of endometrial action at this dosage.     

A novel case of endometrial dedifferentiated adenocarcinoma associated with MLH1 promotor hypermethylation and microsatellite instability

Endometrial dedifferentiated carcinoma is a rare, malignant tumor whose molecular alterations have not been clarified yet. We report a novel case of a 61-year old woman who presented with irregular vaginal bleeding after menopause and a 3?cm uterus mass. Histology revealed endometrial dedifferentiated adenocarcinoma, a rare subtype comprised of undifferentiated adenocarcinoma. The patient still survived 1?year after surgery without chemotherapy and radiotherapy. Immunohistochemistry revealed loss of MLH1/PMS2 expression and retained MSH2/MSH6 expression. Consistently, microsatellite instability was detected indicative of high microsatellite instability (MSI-H). No BRAF V600E, KRAS and POLE mutations were identified. Remarkably, the promoter regions of mutL homolog 1(MLH1) were methylated. Furthermore, several tumor cells were PD-L1 positive in this case with a concentration at the infiltrating tumor edge indicating MSI-H in endometrial dedifferentiated adenocarcinoma is a potential predictive factor for response to immunotherapy targeting the PD-1 or its ligand PD-L1.     

Prediction of coexistent carcinomas risks by subjective EIN diagnosis and comparison with WHO classification in endometrial hyperplasias

Endometrial intraepithelial neoplasia (EIN) classification is proposed as a new diagnostic system to resolve the limitations of the World Health Organization (WHO) classification in routine practice. Our aim was to find out whether EIN classification excels the WHO classification regarding the accurate prediction of coexisting endometrial carcinomas (EC) in biopsy specimens.