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Endometrial cancer - Top 30 Publications

Risk Factors for Unsuccessful Office-Based Endometrial Biopsy: a Comparative Study of Office-Based Endometrial Biopsy (Pipelle) and Diagnostic Dilation and Curettage (D&C).

To determine the risk factors for Pipelle diagnostic failure, which might help health care providers to choose the appropriate protocol for endometrial evaluation individually.

Prognosis and Treatment of Positive Peritoneal Cytology in Early Endometrial Cancer: Matched Cohort Analyses from the National Cancer Database.

While positive peritoneal cytology is no longer included among the endometrial cancer staging criteria, FIGO recommends continued collection of pelvic washings for cytology in order to produce additional data that may be used to determine the significance of positive cytology for prognosis and treatment of endometrial cancer.

New paradigms for endometrial cancers treatment!

Predictors of malignancy in endometrial polyps: study of 421 women with postmenopausal bleeding.

There is lack of consensus as whether benign-looking endometrial polyps should be removed in postmenopausal women. To help inform clinical practice, this study was conducted to quantify the prevalence and identify the predictors of hyperplasia and cancer in polyps.

miR-145 targets the SOX11 3'UTR to suppress endometrial cancer growth.

To explore the functions of SOX (Sex determining Region Y-related HMG-box) family genes in endometrial cancer (EC) and determine the influence of miR-145/SOX11 on EC cell functions. The relationship between miR-145 and SOX11 was confirmed using TargetScan, miRNA databases and dual-luciferase reporter gene assays. The expression of SOX11 mRNA in tissue specimens was examined using RT-qPCR, while SOX11 protein expression in tissues and cell lines were detected through immunohistochemistry (IHC) and western blotting. After transfection using Lipofectamine 2000, the proliferation, migration, invasion and apoptosis of ECC-1 and HEC-1-A cells were assessed through colony formation, transwell and flow cytometry assays. The correlation of SOX11 expression with the prognosis outcomes of patients was analyzed using Kaplan-Meier analysis and the log-rank test. SOX11 showed high expression in EC, which is negatively correlated with a poor prognostic outcome of EC patients. The expression of miR-145 was lower in EC tissues than in adjacent tissues. MiR-145 significantly reduced the expression of SOX11. In ECC-1 cells, miR-145 suppressed the propagation, migration, and invasion of cells and promoted cell apoptosis. MiR-145 also inhibited the proliferation, migration, and invasion of HEC-1-A cells and facilitated cell apoptosis by inhibiting SOX11. MiR-145 targeted site 3 (3615) of the SOX11 3'UTR to affect the expression of SOX11. MiR-145 and its target gene SOX11 could serve as diagnostic markers for EC. MiR-145 targets the SOX11 3'UTR to inhibit its expression and suppress the propagation and metastasis of EC cells.

ER and PR expression and survival after endometrial cancer.

To measure association between endometrial carcinoma ER and PR status and endometrial cancer (EC) survival, accounting for inter-observer variation.

p27kip1 as a key regulator of endometriosis.

p27kip1 as a key regulator of endometriosis Gonçalves GA p27kip1 is a cyclin-dependent kinase (CDK) inhibitor whose specific late G1 destruction allows progression of the cell across the G1/S boundary. There is a direct relationship between low level of p27 and rapid proliferation occurring in several benign states and in many malignances. In the glandular cells of the normal endometrium, the level of p27kip1 is exceedingly low during the proliferative phase, whereas it is markedly increased during the secretory phase. The expression of p27kip1 in endometriosis is very low but has been found to increase following treatment with progesterone. However, estrogen exposure is considered as a major risk factor in developing endometrial cancer. Endometriosis endometrial cells cultures have also lower levels of p27kip1 compared to heath endometrial cells cultures and restore the cell cycle balance when transduced with an adenoviral vector carring the p27kip1 coding gene (Adp27EGFP). More uniform and rigorous studies are required to confirm these and additional markers utility in a diagnostic and possible treatment panel. As a major clinical priority is to determine which lesions can be treated medically and which require surgical intervention, focusing future studies on markers that distinguish response to hormone therapy or are involved in hormone regulation, will be important future considerations. The goal of this highlight review is to provide a broad overview of the advancements in studies about endometriosis mainly correlating the cytokine p27kip1 expression with the diagnostic and disease treatment.

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

To assess efficacy of the levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of complex atypical hyperplasia or low-grade endometrial cancer.

New therapies for advanced, recurrent, and metastatic endometrial cancers.

Endometrial cancer is the most common gynecologic malignancy in the United States, accounting for 6% of cancers in women. In 2017, an estimated 61,380 women were diagnosed with endometrial cancer, and approximately 11,000 died from this disease. From 1987 to 2008, there was a 50% increase in the incidence of endometrial cancer, with an approximate 300% increase in the number of associated deaths. Although there are many chemotherapeutic and targeted therapy agents approved for ovarian, fallopian tube and primary peritoneal cancers, since the 1971 approval of megestrol acetate for the palliative treatment of advanced endometrial cancer, only pembrolizumab has been Food and Drug Administration (FDA)-approved for high microsatellite instability (MSI-H) or mismatch repair deficient (dMMR) endometrial cancer; this highlights the need for new therapies to treat advanced, recurrent, metastatic endometrial cancer. In this review, we discuss current and emerging treatment options for endometrial cancer, including chemotherapy, targeted therapy, and immunotherapy. The National Cancer Institute (NCI) and others are now focusing their efforts on the design of scientifically rational targeted therapy and immunotherapy trials for specific molecular phenotypes of endometrial cancer. This is essential for the advancement of cancer care for women, which is threatened by a severe enrollment decline of approximately 80% for gynecologic oncology clinical trials.

Role of blue dye for sentinel lymph node detection in early endometrial cancer.

Sentinel Lymphonode analysis has become a barely new and innovative way to treat early stages of endometrial cancer (Ballester et al., Lancet Oncol 469-476, 2011; Buda et al., Ann Surg Oncol 2975-81, 2016). Indocyanine green cervical injection is considered gold standard for mapping nodes' drainage. Blue dye is used as a valid alternative in many centers, due to the lower cost of execution. The objective of this video is to prove that methylene blue dye's cervical injection is a valid and "low-cost" method to obtain mapping of lymphatic drainage in patient with early endometrial cancer.

Clinical trials in gynecologic oncology: Past, present, and future.

The Gynecologic Oncology Group has historically performed ground-breaking, practice-changing clinical trials in women's cancers. The current standard of care for initial treatment of ovarian, endometrial, cervical, and trophoblastic cancers was determined by clinical trials completed within this cooperative group structure. For example, trial GOG-0111 set the standard for combining platinum and taxane chemotherapy in ovarian cancer, and more recently GOG-0240 provided evidence for adding bevacizumab to chemotherapy for women with advanced cervical cancer. The landscape of clinical trial design has markedly changed in recent decades, with a clear emphasis on streamlining drug development towards specific patient populations and indications for investigational agents. Translational science in gynecologic cancers can set the stage for rapid and efficient introduction of new therapies for our patients. The gynecologic oncology community of researchers and clinicians is well positioned to enter into the new era of drug development, with breakthrough discoveries increasing each year. It is clear that we must incorporate smarter clinical trial design to get the right drugs to the right patients expeditiously, so we can continue to improve outcome for women with gynecologic cancers.

Molecular Modifiers of Hormone Receptor Action: Decreased Androgen Receptor Expression in Mismatch Repair Deficient Endometrial Endometrioid Adenocarcinoma.

Endometrial endometrioid carcinoma is related to estrogen excess and expression of estrogen and progesterone receptors. Epidemiological evidence suggests that exposure to elevated androgens, as in polycystic ovarian syndrome, increases the risk of endometrial cancer. Factors impacting androgen receptor (AR) expression are not well studied. Mismatch repair (MMR) deficiency due to MLH1 gene methylation is one of the most common molecular alterations in endometrial cancer, occurring in 15% to 20% of cases. MLH1 methylation can be associated with decreased expression of other genes, so we examined the effect of MMR status on AR expression. As NF-κB is known to induce AR, this transcription factor was also examined. Three hundred forty-four unselected endometrial carcinomas were evaluated for DNA MMR. Loss of expression of MLH1 with MLH1 methylation was defined as MMR deficient, and positive expression of MMR proteins was defined as MMR intact. A case-control cohort of 96 grade 2 endometrioid carcinomas was studied from this set (47 MMR deficient, 49 MMR intact). Cases were matched for histotype, grade, and age. AR and NF-κB immunohistochemical expression were evaluated by 2 different scoring systems (CAP/ASCO and Allred) used for estrogen receptor. Despite higher levels of NF-κB, MMR deficiency was associated with a significantly lower mean percentage of AR expression. The MMR deficient group had more variable AR expression, with more cases scoring on the lower end of the spectrum. These findings have implications for clinical trials of AR antagonists in gynecologic cancers.

Uterine function: from normal to Polycystic Ovarian Syndrome alterations.

The endometrium is one of the most important female reproductive organs. Polycystic ovarian syndrome (PCOS) is a reproductive and endocrine pathology that affect women of reproductive age. PCOS negatively affects the endometrium, leading to implantation failure and proliferative aberrations.

A Rare Case of Endometrial Cancer Metastatic to the Sigmoid Colon and Small Bowel.

Metastatic endometrial cancer to the small bowel or colon has been described but is quite rare. We present a case of metastatic endometrial cancer with synchronous metastases to the colon and jejunum identified three years after surgical treatment of early stage endometrial cancer.

Guiding histological assessment of uterine lesions using 3D in vitro ultrasonography and stereotaxis.

To compare ultrasonographic features of uterine lesions with the findings at macroscopy and microscopy.

The role of EpCAM in tumor progression and the clinical prognosis of endometrial carcinoma.

EpCAM is a transmembrane glycoprotein that functions as an epithelial marker in endometrial tissues. However, the correlation between EpCAM and endometrial carcinoma (EC) is not clear.

The Effect of Soy Isoflavones on the Menopause Rating Scale Scoring in Perimenopausal and Postmenopausal Women: A Pilot Study.

Menopause is associated with many unpleasant symptoms which vary in different phases of menopausal transition. Although, Hormone Replacement Therapy (HRT) is considered the most effective mode of treatment for these symptoms, its use is associated with increased risk of breast cancer, endometrial cancer and thromboembolic events. Soy isoflavones are being widely used as a safer alternative to HRT, even though scientific evidence of their efficacy is poor or lacking.

Dietary n-3 polyunsaturated fatty acids, fish consumption, and endometrial cancer risk: a meta-analysis of epidemiological studies.

The relationship between intake of fish and n-3 fatty acids and endometrial cancer risk has not been consistent across epidemiological studies. We quantitatively assessed the aforementioned association through a systematic review and meta-analysis. PubMed and Embase were searched through March 2017 for eligible epidemiological studies. Fixed or random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs). The dose-response relationship was also evaluated. Based on the literature search, five prospective studies and 11 case-control studies were identified. All 16 studies were categorized as high-quality studies. After pooling available risk estimates, no significant association was detected between overall fish intake and endometrial cancer risk. In subgroup analyses, every one additional serving/week of fish intake was significantly associated with inversed endometrial cancer risk in studies adjusted for smoking (RR (95% CI): 0.95 (0.91-1.00)), or studies performed in Europe (RR (95% CI): 0.90 (0.84-0.97)), but not in other tested subgroups. In studies conducted in Asia, there was significant positive association (RR (95% CI): 1.15 (1.10-1.21)). Regarding n-3 PUFA intake, marginally inverse associations of high EPA or DHA intake were detected (EPA: RR (95% CI) = 0.79 (0.61-1.04); DHA: RR (95% CI) = 0.85 (0.64-1.11)). Dose-response analyses suggested a significant nonlinear relationship between DHA intake and endometrial cancer risk (p: 0.04). Overall, this meta-analysis suggests that intake of n-3 PUFA may be inversely associated with endometrial cancer risk at some level of evidence, although the exact relationship, especially for fish intake, needs further characterization. Further well-designed studies are warranted.

The positivity of G-protein-coupled receptor-30 (GPR 30), an alternative estrogen receptor is not different between type 1 and type 2 endometrial cancer.

It is well-known that the clinical outcomes are different between type 1 (estrogen dependent) and type 2 (estrogen independent) endometrial cancer. Studies have suggested that the estrogen receptor (ER) is positively correlated with endometrial cancer survival, however we previously reported that there is no difference in the positivity of ER as well as sex hormone levels between subtypes of cancer. G-protein-coupled receptor-30 (GPR 30), an alternative estrogen receptor has been suggested to be negatively correlated with clinical outcomes of endometrial cancer. In this study we investigated whether the positivity of GPR30 is different between subtypes of cancer. The immunostaining of GPR30 and ER was examined and analysed in 128 cases taking into account menopausal status. Overall, 105 (82%) cases were GPR30 positive and 118 (92%) cases were ER positive. The positivity of GPR30 in type 1 endometrial cancer (83%) was not statistically different to type 2 endometrial cancer (78%). In addition, intensity of immunostaining of GPR30 in type 1 endometrial cancer was also not different to type 2 endometrial cancer quantified by semi-quantitative analysis (p = 0.268). Menopausal status was not associated with the positivity of GPR30 in both type 1 and type 2 endometrial cancer. Furthermore, the positivity and intensity of immunostaining of GPR30 were not correlated with the positivity and intensity of immunostaining of ER in endometrial cancer (p = 0.689). Our data further confirm that type 2 endometrial cancer may not be completely estrogen independent, and suggest that type 1 and type 2 endometrial cancer may have similar pathogenesis.

Progestin-associated shift of meningioma mutational landscape.

Meningiomas are the most common primary tumor of the central nervous system. The relationship between meningioma and progestins is frequently mentioned but has not been elucidated.

Loss of polarity alters proliferation and differentiation in low-grade endometrial cancers by disrupting Notch signaling.

Cell adhesion and apicobasal polarity together maintain epithelial tissue organization and homeostasis. Loss of adhesion has been described as a prerequisite for the epithelial to mesenchymal transition. However, what role misregulation of apicobasal polarity promotes tumor initiation and/or early progression remains unclear. We find that human low-grade endometrial cancers are associated with disrupted localization of the apical polarity protein Par3 and Ezrin while, the adhesion molecule E-cadherin remains unchanged, accompanied by decreased Notch signaling, and altered Notch receptor localization. Depletion of Par3 or Ezrin, in a cell-based model, results in loss of epithelial architecture, differentiation, increased proliferation, migration and decreased Notch signaling. Re-expression of Par3 in endometrial cancer cell lines with disrupted Par3 protein levels blocks proliferation and reduces migration in a Notch dependent manner. These data uncover a function for apicobasal polarity independent of cell adhesion in regulating Notch-mediated differentiation signals in endometrial epithelial cells.

Synthetically lethal nanoparticles for treatment of endometrial cancer.

Uterine serous carcinoma, one of the most aggressive types of endometrial cancer, is characterized by poor outcomes and mutations in the tumour suppressor p53. Our objective was to engender synthetic lethality to paclitaxel (PTX), the frontline treatment for endometrial cancer, in tumours with mutant p53 and enhance the therapeutic efficacy using polymeric nanoparticles (NPs). First, we identified the optimal NP formulation through comprehensive analyses of release profiles and cellular-uptake and cell viability studies. Not only were PTX-loaded NPs superior to PTX in solution, but the combination of PTX-loaded NPs with the antiangiogenic molecular inhibitor BIBF 1120 (BIBF) promoted synthetic lethality specifically in cells with the loss-of-function (LOF) p53 mutation. In a xenograft model of endometrial cancer, this combinatorial therapy resulted in a marked inhibition of tumour progression and extended survival. Together, our data provide compelling evidence for future studies of BIBF- and PTX-loaded NPs as a therapeutic opportunity for LOF p53 cancers.

OCDD: an obesity and co-morbid disease database.

Obesity is a medical condition that is known for increased body mass index (BMI). It is also associated with chronic low level inflammation. Obesity disrupts the immune-metabolic homeostasis by changing the secretion of adipocytes. This affects the end-organs, and gives rise to several diseases including type 2 diabetes, asthma, non-alcoholic fatty liver diseases and cancers. These diseases are known as co-morbid diseases. Several studies have explored the underlying molecular mechanisms of developing obesity associated comorbid diseases. To understand the development and progression of diseases associated with obesity, we need a detailed scenario of gene interactions and the distribution of the responsible genes in human system.

BCOR Internal Tandem Duplication in High-grade Uterine Sarcomas.

Endometrial stromal sarcomas (ESSs) are mesenchymal uterine tumors characterized by recurrent genetic events, most commonly chromosomal rearrangements, that create oncogenic gene fusions. High-grade endometrial stromal sarcomas (HG-ESSs), as defined in the 2014 World Health Organization Classification, typically contain oncogenic YWHAE-NUTM2 fusions; however, although not well characterized, there are tumors morphologically overlapping with HG-ESS that do not contain the YWHAE-NUTM2 fusions. These fusions are also found in certain pediatric primitive sarcomas, including clear cell sarcoma of the kidney and soft tissue undifferentiated round cell sarcoma of infancy. A subset of these same pediatric sarcomas lack YWHAE-NUTM2 fusions and instead have internal tandem duplications (ITDs) involving exon 15 of BCOR (BCOR ITD). We investigated the presence of BCOR ITD by targeted sequencing in a series of 31 uterine sarcomas, comprising 5 low-grade ESS, 13 uterine sarcomas diagnosed as HG-ESS, and 13 undifferentiated uterine sarcomas. BCOR ITD were present in 1 uterine sarcoma diagnosed as HG-ESS and 2 undifferentiated sarcomas with uniform nuclear features, all of which lacked any of the recurrent chromosome translocations known to occur in ESS. These 3 high-grade sarcomas with BCOR ITD affected young patients (average age, 24) and morphologically were composed of nonpleomorphic spindle cells admixed with epithelioid and round cell areas. Focal myxoid stroma was present in 2 cases. Mitotic activity was brisk, necrosis was present, and there was lymphovascular involvement in all cases. The 3 uterine sarcomas with BCOR ITD exhibited diffuse cyclin D1 immunohistochemical expression and there was diffuse BCOR expression in the 2 cases tested. Long-term follow-up in 2 patients revealed 1 to be tumor-free after 22 years and the other to die of disease after 8 years. In conclusion, BCOR ITD is an oncogenic alternative to YWHAE-NUTM2 fusion in high-grade uterine sarcomas with uniform nuclear features. We propose that neoplasms with the morphology described and BCOR ITD be regarded as a unique subtype of high-grade uterine sarcoma, possibly within the family of endometrial stromal neoplasia.

Role of Systematic Lymphadenectomy to Tailor Adjuvant Therapy in Early Endometrial Cancer.

The long-standing protocol at our center for apparent stage I and II endometrial cancers comprises hysterectomy and bilateral salpingo-oophorectomy without lymphad-enectomy. Adjuvant treatment is based in line with Postoperative Radiation Therapy in Endometrial Carcinoma 1 protocol. Our aim was to quantify the number of patients who would avoid external beam radiation therapy (EBRT) in our institution if we adopted a protocol of lymphadenectomy to tailor adjuvant EBRT and its impact on cost and quality of life.

Radiation therapy improves disease-specific survival in women with Stage II endometrioid endometrial cancer-Brachytherapy may be sufficient.

To evaluate disease-specific survival (DSS) outcomes in Stage II endometrioid endometrial cancer (EC) patients based on pathology and treatment information including adjuvant radiotherapy and lymph node assessment.

Ovarian mucinous borderline tumor accompanied by LGESS with myxoid change: a case report and literature review.

To report an extremely rare case of ovarian borderline mucinous cystic tumor accompanied by low-grade endometrial stromal sarcoma (LGESS) with myxoid change.

Laparoscopic pelvic lymphadenectomy in patients with intermediate-risk endometrial cancer: Is it worth it?

The main aim of this study is to evaluate operative and postoperative morbidity of laparoscopic pelvic lymphadenectomy as well as its potential impact on the postoperative management in patients with an intermediate-risk of endometrial cancer.

Worldwide burden of cancer attributable to diabetes and high body-mass index: a comparative risk assessment.

Diabetes and high body-mass index (BMI) are associated with increased risk of several cancers, and are increasing in prevalence in most countries. We estimated the cancer incidence attributable to diabetes and high BMI as individual risk factors and in combination, by country and sex.