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Endometrial cancer - Top 30 Publications

Metabolomic and Lipidomic Profiling Identifies The Role of the RNA Editing Pathway in Endometrial Carcinogenesis.

Endometrial cancer (EC) remains the most common malignancy of the genital tract among women in developed countries. Although much research has been performed at genomic, transcriptomic and proteomic level, there is still a significant gap in the metabolomic studies of EC. In order to gain insights into altered metabolic pathways in the onset and progression of EC carcinogenesis, we used high resolution mass spectrometry to characterize the metabolomic and lipidomic profile of 39 human EC and 17 healthy endometrial tissue samples. Several pathways including lipids, Kynurenine pathway, endocannabinoids signaling pathway and the RNA editing pathway were found to be dysregulated in EC. The dysregulation of the RNA editing pathway was further investigated in an independent set of 183 human EC tissues and matched controls, using orthogonal approaches. We found that ADAR2 is overexpressed in EC and that the increase in expression positively correlates with the aggressiveness of the tumor. Furthermore, silencing of ADAR2 in three EC cell lines resulted in a decreased proliferation rate, increased apoptosis, and reduced migration capabilities in vitro. Taken together, our results suggest that ADAR2 functions as an oncogene in endometrial carcinogenesis and could be a potential target for improving EC treatment strategies.

SOX15 regulates proliferation and migration of endometrial cancer cells.

The study aimed to investigate the effects of SOX15 on proliferation and migration of endometrial cancer (EC) cells. Immunohistochemistry was applied to determine the expression of SOX15 in EC tissues and adjacent tissues. We used cell transfection method to construct the HEC-1-A and Ishikawa cell lines with stable overexpression and low-expression SOX15 Reverse transcription quantitative real-time PCR (RT-qPCR) and western blot were performed to examine expression of SOX15 mRNA and SOX15 protein respectively. By conducting a series of cell proliferation assay and migration assay, we analyzed the influence of SOX15 overexpression or low-expression on EC cell proliferation and migration. The expression of SOX15 mRNA and protein in EC tissues was significantly lower than that in adjacent tissues. After lentivirus-transfecting SOX15 , the expression level of SOX15 mRNA and protein was significantly increased in cells of SOX15 group, and decreased in sh- SOX15 group. Overexpression of SOX15 could suppress cell proliferation, while downregulation of SOX15 increased cell proliferation. Flow cytometry results indicated that overexpression of SOX15 induced the ratio of cell cycle arrest in G1 stage. In addition, transwell migration assay results showed that SOX15 overexpression significantly inhibited cell migration, and also downregulation of SOX15 promoted the migration. As a whole, SOX15 could regulate the proliferation and migration of EC cells and upregulation of SOX15 could be valuable for EC treatment.

Surgical Findings and Outcomes in Premenopausal Breast Cancer Patients Undergoing Oophorectomy: a Multicenter Review From the Fellows' Pelvic Research Network.

Since publication of the Suppression of Ovarian Function Trial (SOFT) data, some women with premenopausal breast cancer have been recommended to undergo bilateral oophorectomy to facilitate breast cancer treatment with aromatase inhibitors. These women may be at higher risk of occult abdominal pathology than the general population. Our objective is to describe the procedures performed, intra-abdominal findings, and surgical pathology of this population.

Importance of PCR-based Tumor Testing in the Evaluation of Lynch Syndrome-associated Endometrial Cancer.

Lynch syndrome (LS) is a hereditary cancer syndrome caused by a germline mutation in a DNA mismatch repair gene, usually MLH1, MSH2, MSH6, or PMS2. The most common cancers associated with LS are colorectal adenocarcinoma and endometrial carcinoma. Identification of women with LS-associated endometrial cancer is important, as these women and their affected siblings and children are at-risk of developing these same cancers. Germline testing of all endometrial cancer patients is not cost effective, and screening using young age of cancer diagnosis and/or presence of family history of syndrome-associated is underutilized and ineffective. Therefore, most groups now advocate for tumor tissue testing to screen for LS, with germline testing targeted to women with abnormal tissue testing results. Immunohistochemistry for MLH1, MSH2, MSH6, and PMS2 is used in many clinical laboratories for this tumor screening step, as immunohistochemistry is relatively inexpensive and is technically more accessible for smaller clinical labs. PCR-based tissue testing, whereas technically more challenging, does play an important role in the identification of these patients. MLH1 methylation analysis identifies women with tumor MLH1 loss who likely have sporadic endometrial cancer and do not need heightened cancer prevention surveillance. High levels of microsatellite instability have been identified in tumors with retained positive expression of mismatch repair proteins. Somatic sequencing of mismatch repair genes from tumor DNA, whereas not currently available in most clinical laboratories, is helpful in resolution of cases in which germline sequencing fails to identify a mutation in a mismatch repair gene. The tumor tissue testing approach can help to identify most women at-risk for germline mutations in a LS gene, but not all patients will be captured using this approach. Clinical suspicion can still play a pivotal role in accurately identifying a subset of these patients.

Using rating of perceived exertion in assessing cardiorespiratory fitness in endometrial cancer survivors.

For cancer survivors, who also often present with co-existing health conditions, exercise testing is often performed using submaximal protocols incorporating linear heart rate response for estimating the cardiorespiratory capacity and assessing exercise tolerance. However, use of beta-blocker medications, during sub-maximal protocols based on linear HR response can be problematic. Rating of perceived exertion (RPE), which takes into account an individual's overall perception of effort, can be used as a complementary tool that does not rely solely on the heart rate response to increased workload. We compared heart rate response (VO2HR) and self-rating of perceived exertion (VO2RPE) in a graded submaximal exercise test (GXT) in 93 endometrial cancer survivors. The results of the GXT were stratified according to whether participants were taking beta-blocker (BB) medications or not (non-BB). Among non-BB participants, there was no difference between the mean VO2HR and the mean VO2RPE estimates of cardiorespiratory capacity (mlO2//kg/min) (20.4 and 19.3, respectively; p = 0.166). Among BB participants, the mean VO2HR approached significant difference than the mean VO2RPE (21.7 mlO2//kg/min and 17.6 mlO2//kg/min, respectively; p = 0.087). Bland-Altman plots for both methods showed a proportional bias for the non-BB group; but not the BB group. Our results suggest that sub-maximal protocols based on Borg's Rating of Perceived exertion (RPE) produce differing results from sub-maximal protocols based on HR response when applied to clinical population taking BB medications. Using RPE instead of HR for participants on BB medications may be a better method for assessing the exercise tolerance for estimating the cardiorespiratory capacity in sub-maximal exercise testing.

The presence of A5935G, G5949A, G6081A, G6267A, T9540C mutations in MT-CO1 and MT-CO3 genes and other variants of MT-CO1 and MT-CO3 gene fragments in the study population diagnosed with endometrial cancer.

The specific purpose of this study was the assessment of A5935G, G5949A, G6081A, G6267A mutations in MT-CO1 and T9540C in MT-CO3, and alterations detected during the analysis of MT-CO gene fragments in subject and control groups. A secondary aim was to assess the relationship between MT-CO1 and MT-CO3 gene alterations and endometrial cancer incidence and evaluation of the prognostic value of MT-CO1 and MT-CO3 gene alterations.

Sporadic endometrial adenocarcinoma with MMR deficiency due to biallelic MSH2 somatic mutations.

The invalidation of the Mismatch Repair (MMR) system is responsible for a so-called "deficient MMR" phenotype (dMMR) characterized by microsatellite instability and abnormal pattern of expression of MMR proteins in tumor tissue. This phenotype occurs in at least 20% of sporadic endometrial adenocarcinomas by epigenetic silencing of MLH1 gene. It is also observed in virtually all tumors occurring in patients with Lynch syndrome by monoallelic germline mutation in one of the MMR genes. The determination of this phenotype (dMMR vs. proficient MMR-pMMR) has therefore a pivotal place in the diagnosis algorithm for Lynch syndrome by monoallelic germline mutation in one of the MMR genes. The determination of this phenotype (dMMR vs. proficient MMR-pMMR) has therefore a pivotal place in the diagnosis algorithm for Lynch syndrome. We report the case of a woman with an early-onset endometrial adenocarcinoma who was suspected to be affected with Lynch syndrome based on tumor dMMR phenotype (MSI associated with loss of expression of MSH2 and MSH6 proteins). After complete germline and somatic evaluations, this phenotype was eventually explained by two MSH2 somatic mutations and the diagnosis of Lynch-like syndrome due to an unidentified MSH2 germline mutation was ruled out. Somatic mosaicism at low mutation rate was unlikely as no mutation was detected by DNA analysis from various tissue samples. Nevertheless, the three patient's children were tested for the two mutations and these tests were negative. Biallelic somatic mutations of one MMR gene is a mechanism of invalidation of the MMR system in sporadic cases. Clinicians have to be aware of this mechanism because of the great clinical implication for the patients and their relatives.

Expression of CD133 in endometrial cancer cells and its implications.

Cancer stem cells are an attractive therapeutic target for cancer. The present study examined stem cell characteristics of CD133+ cells isolated from endometrial cancer. Phenotypic characteristics, proliferation, migration, anchorage-independent growth, chemoresistance, gene expression profile and tumorigenicity of CD133+ tumor cells were assessed. Primary tumor exhibited immunoreactivity for CD133. Endometrial CD133+ tumor cells enhanced proliferation rate, colony formation, chemotaxis migration ability, and chemoresistance to cisplatin, paclitaxel, and doxorubicin than CD133- cells. CD133+ cells expressed more cancer stem cells markers such as EpCAM, aldehyde dehydrogenase 1 and insulin-like growth factor-1 receptor than CD133- cells. Moreover, CD133+ cells also increased expression of embryonic stem cell markers including oct4, nanog, sox2, and cmyc than CD133- cells. Finally, CD133+ tumor cells could generate xenograft but not CD133- tumor cells. CD133 and Ki67 were extensively expressed in the xenograft. In conclusion, endometrial CD133+ tumor cells displayed cancer stem cell characteristics and might represent a valuable tool for identifying endometrial cancer stem cells and hence a potential therapeutic target.

Sitting, physical activity, and serum oestrogen metabolism in postmenopausal women: the Women's Health Initiative Observational Study.

Prolonged sitting and lower levels of physical activity have been associated with increased levels of parent oestrogens (oestrone and oestradiol), the key hormones in female cancers, in postmenopausal women. However, it is unknown whether sitting and physical activity are associated with circulating oestrogen metabolite levels.

Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women's Health Initiative Observational Study.

To determine the association between use of vaginal estrogen and risk of a global index event (GIE), defined as time to first occurrence of coronary heart disease (CHD), invasive breast cancer, stroke, pulmonary embolism, hip fracture, colorectal cancer, endometrial cancer, or death from any cause.

Clinical indications for hysteroscopic removal of uterine masses: Time, age at diagnosis, and mass size.

The aim of this study was to investigate clinical factors associated with abnormal pathologies of uterine masses resected via hysteroscopy.

Risk of second primary cancers in women diagnosed with endometrial cancer in German and Swedish cancer registries.

Along with the increasing incidence and favorable prognosis, more women diagnosed with endometrial cancer may develop second primary cancers (SPCs). We aimed at investigating risk of SPCs after endometrial cancer in Germany and Sweden to provide insight into prevention strategies for SPCs. Endometrial cancer patients diagnosed at age ≥15 years in Germany during 1997-2011 and in Sweden nationwide during 1997-2012 were selected. Standardized incidence ratios (SIRs), calculated as the ratio of observed to expected numbers of cases, were used to assess the risk of a specific second cancer after endometrial cancer for both German and Swedish datasets. Among 46,929 endometrial cancer survivors in Germany and 18,646 in Sweden, overall 2,897 and 1,706 SPCs were recorded, respectively. Significantly elevated SIRs were observed in Germany for ovarian (SIR=1.3; 95%CI:1.1-1.5) and kidney cancers [1.6 (1.3-1.8)], while in Sweden the SIRs were 5.4 (4.6-6.3) and1.4 (1.0-1.9), respectively. Elevated risk for second ovarian endometrioid carcinoma was pronounced after early (<55 years) onset endometrial cancer in Germany [9.0 (4.8-15)] and Sweden [7.7 (5.1-11)]. In Germany elevated risks were found for second ovarian endometrioid carcinoma after endometrioid histology of first endometrial cancer [6.3 (4.0-9.4)] and for second kidney cancer after clear cell histology of endometrial cancer [4.9 (1.6-11)]. We found exceptionally elevated risk of second ovarian endometrioid carcinoma after endometrial cancer of the same histology or of early onset. Risk for second kidney cancer was also increased, particularly after endometrial cancer of clear cell histology. Cancer prevention strategies should focus on these cancers after endometrial cancer diagnosis. This article is protected by copyright. All rights reserved.







Integrated Mindfulness-Oriented Recovery Enhancement (MORE) and physical health intervention for cancer survivors with obesity: Preliminary results from a pilot randomized controlled trial.

237 Background: Hypothetically, interventions that reduce excessive weight and promote nutrition and physical activity may protect against cancer recurrence. Yet, obesity is often fueled by compulsive eating behaviors. Integrative therapies that combine exercise and nutrition training with techniques to enhance interoceptive awareness and cognitive control over automatic, compulsive eating may be especially efficacious. This pilot study tested the preliminary efficacy of an integrated exercise, nutrition, and Mindfulness-Oriented Recovery Enhancement (MORE) intervention in a sample of obese cancer patient.

Prospective study to evaluate impact of support group participation in women with gynecological cancer.

243 Background: Unlike breast cancer support group literature, there is no data in women with gynecologic cancers who have different perspective about their disease and therapy. We have a well-established (10 years old) active grass root level support group unique to women with gynecologic cancers that meets monthly. Our goal was to investigate perceived benefits of support group participation.

Understanding causes of distress in women with gynecologic cancer.

94 Background: Lay patient navigators can screen patients using a distress tool (DT) to identify and address multiple patient concerns. Patient-reported distress can be used to characterize the needs of patients with ovarian, endometrial, and cervical cancer through all phases of care from initial diagnosis through active treatment and into survivorship.

Molecular profiling of triple-negative endometrial cancers (TNEC) and triple-negative breast cancers (TNBC) to reveal unique expression profiles.

159 Background: "Triple negative" has been used to characterize a subtype of breast cancer that lacks estrogen, progesterone, and HER2 receptor expression. They are aggressive cancers with limited treatment options. It's unknown if similar phenotype found in other cancer types, like endometrial cancer, harbor similar molecular alterations and prognosis. We aim to compare molecular features between TNEC and TNBC.

Evaluating the impact of a clinical universal mismatch repair screening initiative.

194 Background: Immunohistochemistry (IHC)-based universal mismatch repair (UMMR) screening of incident colorectal (CRC) and endometrial (EC) tumors for deficient MMR (dMMR) associated with Lynch syndrome (LS) is supported by expert recommendations and is cost-effective. Heterogeneity in the approach to implementation of UMMR screening nationwide has been observed, suggesting knowledge gaps that could adversely impact anticipated outcomes. Studies of clinical UMMR screening can inform efforts to optimize implementation in the real world setting.

Predictors of failure to perform pelvic peritoneal cytology in endometrial cancer staging surgery.

201 Background: The Federation of Gynecology and Obstetrics (FIGO) staging system and the National Comprehensive Cancer Network (NCCN) guidelines for endometrial cancer recommend performing pelvic peritoneal cytology to look for the presence of cancer cells in the peritoneal cavity in patients who are undergoing surgical staging of apparent non-metastatic disease. About 10% of cases have positive cytology and this information is used in formulating plans for adjuvant therapy. However, adherence to the guidelines recommending that cytology be performed is not universal. In this study, we sought to identify factors associated with failure to perform pelvic peritoneal cytology at the time of endometrial cancer staging surgery.

Understanding variation in the timeliness of diagnosis of cancer in symptomatic patients.

301 Background: Diagnosing cancer promptly in symptomatic patients is a priority for healthcare systems worldwide, but little is known about how initiatives can be targeted to patients at greater risk.

Enabling quality data reporting: National implementation of standardization pathology reporting.

122 Background: The Canadian Partnership Against Cancer (the Partnership) launched its Electronic Synoptic Pathology Reporting Initiative (ESPRI) to advance the implementation and promote the wide adoption of standardized synoptic pathology reporting tools in Canada. This presentation will highlight strategies to ensure successful implementation of this program across the Canadian health system as well as lessons learned.

Secondary nonbreast malignancies (SNBM) after primary breast cancer (BC).

112 Background: BC survivors are at higher risk of developing SNBM due to treatment effects and shared behavioral and genetic factors. Associations between histologic subtypes of primary BC and secondary endometrial or ovarian cancer have been reported. Less is known about subtype-specific associations with other secondary solid tumors. We aimed to determine the prevalence of SNBM across US Oncology practices and what subtype-specific associations, if any, exist between primary BC and SNBM.

Secondary cancers after breast-conserving therapy in Tokyo database.

139 Background: The more patients overcome early breast cancer and become cancer survivors as a result of modern sophisticated approach, the more secondary cancers inevitably arise. The second malignancies after breast conserving therapy (BCT) are well-known sticky dilemma because of additional anxiety and need for medical care for longer-time. However, it is unclear whether secondary cancers negatively affect prognosis of breast cancer survivors.

Evaluation of a cancer gene sequencing panel in a hereditary risk assessment clinic.

7 Background: Multiple-gene sequencing panels are entering clinical practice. We report on research testing with a custom sequencing panel comprising 43 genes and 32 cancer-associated variants among patients referred for assessment of hereditary breast and ovarian cancer risk.

Implementing Lynch syndrome screening utilizing a community partnership.

203 Background: Lynch syndrome (LS) is an autosomal dominant condition associated with an 80% risk of colorectal cancer, a 60% risk of endometrial cancer, and additional risks for extra-colonic cancers. Amsterdam and Bethesda criteria can be used to identify patients who may be at risk. However, 25% of colon cancer and 65% of endometrial cancer patients with LS will be missed by using family history criteria alone. LS is caused by mutations in mismatch repair genes (MMR): MLH1, MSH2, MSH6, PMS2, and EPCAM. Tumor screening by immunohistochemistry (IHC) is available, and abnormal results can be flagged for more definitive genetic counseling and testing. Recommendations from the 2009 EGAPP (Evaluation of Genomic Applications in Practice and Prevention) Working Group concluded there is sufficient evidence to use this tumor testing for LS, and the screening would provide moderate population benefits. Cost effectiveness studies have shown universal screening detects nearly twice as many cases of LS and is < $25,000 per life year saved.