Endometrial Cancer In Women Research Articles

Correlation between abdominal visceral fat and the risk of endometrial cancer in patients with polycystic ovary syndrome

Objective: To explore the correlation between abdominal fat and the occurrence risk of endometrial cancer (EC) in patients with polycystic ovary syndrome (PCOS). Methods: The clinical information of 120 PCOS patients receiving treatment in our hospital from March 2019 to April 2022 were included in this study. Patients were divided into two groups, endometrial cancer (EC, n=35) and normal group (NM, n=85). Statistical analysis included t-test, c2-test, and Pearson's correlation coefficient. We analysed the data using logistic regression. The predictive accuracy and discriminative ability of the prediction model were assessed by the area under the receiver operating characteristic (ROC) curve (AUC) and calibration curves. Results: The incidence rate of EC in women with PCOS is 10.91% (12/110). Significant differences were found in waist circumference, hypertension, diabetes, hyperlipidemia, body mass index (BMI), waist-hip ratio (WHR), insulin resistance index (HOMA-IR), visceral fat area (VFA) oestrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER2), estradiol (E2), and luteinizing hormone (LH) between the two groups (P<0.05). No statistical difference was found in age, hip circumference, menopause, use of intrauterine device, progesterone (P) and follicle-stimulating hormone (FSH) between the groups (P>0.05). Multivariate logistic regression analysis showed that BMI, HOMA-IR, VFA and HER2 were independent influencing factors of EC in PCOS patients (P<0.05). The AUC of BMI, HOMA-IR, VFA, HER2 were 0.878 (95%CI: 0.810~0.946), 0.831 (95%CI: 0.751~0.911), 0.816 (95%CI: 0.704~0.929) and 0.737 (95%CI: 0.634,0.840), respectively. The model had more diagnostic effectiveness (AUC=0.973). Conclusions: In PCOS disease, high-level BMI, HOMA-IR, VFA, and positive HER2 show an increased risk in the incidence of EC. These findings suggest that BMI, HOMA-IR, VFA, and HER2 are potential markers for Risk assessment of EC. HER2: Human epidermal growth factor receptor-2, E2: estradiol, P: progesterone, LH: Luteinizing hormone, FSH: Follicle-stimulating hormone. Keywords: Polycystic ovary syndrome; Abdominal visceral fat; Endometrial cancer; Occurrence risk.

The Potential Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists as a Type of Conservative Treatment of Endometrial Cancer in Women of Reproductive Age: A Review of the Literature and a Call for Study.

Endometrial cancer (EC) is among the most common gynecological malignancies in developed countries and its occurrence has been increasing dramatically in the past few years. An in-depth knowledge of the causes of endometrial cancer, such as unopposed estrogen, insulin resistance, and chronic inflammation, has resulted in the suggestion of numerous interventions to decrease the occurrence of this cancer. Recent research has established a connection between obesity and type 2 diabetes mellitus (T2DM) with a higher chance of developing endometrial cancer, suggesting that insulin resistance is a key factor in its onset. Moreover, evidence from both epidemiological and clinical studies indicates that metformin, a drug used to treat diabetes, could possibly help in the prevention of specific types of cancer such as endometrial cancer. The aim of this study is to explore the possible impact of glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) in the non-surgical management of endometrial cancer. GLP-1 has various functions and is produced when nutrients are consumed. Besides promoting the release of insulin, GLP-1 also suppresses the secretion of glucagon and reduces appetite. Moreover, the fact that GLP-1 receptors are found in different organs and tissues such as the brain, lung, pancreas, stomach, heart, and endometrium indicates that GLP-1RAs have multiple functions. Prior research has shown that it triggers apoptosis in endometrial cancer cells. Nevertheless, the precise physiological function of GLP-1 receptors in endometrial cancer still needs to be fully understood.

DNA methylation detection is a significant biomarker for screening endometrial cancer in premenopausal women with abnormal uterine bleeding

ObjectiveThe aim of our study was to explore the value of DNA (CDO1m/CELF4m) methylation detection in exfoliated cervical cells collected for screening endometrial cancer in premenopausal women with abnormal uterine...

The Role of Transvaginal Ultrasonography in the Evaluation of Postmenopausal Bleeding

Background: Endometrial cancer is currently the most common malignancy of the female genital tract. Most of the women with endometrial cancer initially present with postmenopausal bleeding (PMB) and may be assessed initially with either endometrial biopsy or transvaginal ultrasonography. Objective: The objective of this study was to evaluate transvaginal ultrasound (TVS) measurement of endometrial thickness (ET) in diagnosing endometrial cancer in women with postmenopausal bleeding. Materials and method: This was a prospective study. Transvaginal ultrasonography and Papanicolaou smear were performed in 291 women presenting with postmenopausal bleeding aged >50 years and were followed up for one year in BIRDEM General Hospital from September 2017 to August 2018. Results: One hundred and seventeen women had an endometrial thickness ≤4 mm and one endometrial cancer (0.85%) was diagnosed in this group. Endometrial biopsy was performed in women who had recurrent bleeding. But in women with an endometrial thickness of ≥5mm (174 out of 291 women), endometrial cancer was diagnosed in 9.77%, atypical hyperplasia in 5.17%, ovarian malignancy in 1.72% and total malignancy was 17.8%. Conclusion: Transvaginal ultrasonography using a ≤4 mm cut-off has high sensitivity for detecting endometrial cancer and can identify women with PMB who are highly unlikely to have endometrial cancer, thereby avoiding more invasive endometrial biopsy. Delta Med Col J. Jan 2021;9(2): 91-95

Redox-state-regulating enzymes have prognostic value in diabetic endometrial cancer patients: impact of statin use?

The incidence of endometrial cancer is increasing, and oxidative stress has been suggested to play a vital role in its carcinogenesis. Statins have an impact on the cellular redox-state. The aim of this study was to determine the effects of statin use on redox-state regulating enzymes in endometrial cancer in women with type 2 diabetes. This retrospective study consisted of 119 women with type 2 diabetes who were diagnosed with endometrial cancer at Oulu University Hospital in Finland between 2007 and 2014. There were 58 statin users and 61 non-users based on medication use at the time of endometrial cancer diagnosis. The expression of redox-state regulating proteins nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) in the tumor samples was assessed immunohistochemically, and manganese superoxide dismutase (MnSOD) levels were measured both immunohistochemically and from serum samples. High MnSOD expression predicted better progression-free survival (PFS) in statin non-users in a univariate analysis (p=0.02). There was no statistical difference in overall survival (OS) or PFS between strong and weak expression of Nrf2 and Keap1. After adjusting for stage and statin use, the results were similar. Statin non-users with strong MnSOD expression had better PFS compared to statin users which proves that statins have impact on redox-state regulating enzymes. However, these findings are preliminary and require further research.

Lynch syndrome in Mexican-Mestizo families: Genotype, phenotypes, and challenges in cascade testing among relatives at risk

Lynch syndrome (LS) is the most frequent cancer predisposition syndrome affecting the colon and rectum. A pathogenic variant (PV) disrupting one of the mismatch repair (MMR) genes is responsible for the disease. The spectrum of tumors in LS is heterogeneous and includes cancer of the colon and rectum (CRC), endometrium, ovaries, stomach, small bowel, urinary tract, bladder, pancreas, and skin. Knowledge of the phenotypic variation of patients with LS, the type and frequency of PVs, and cascade testing studies in the Latin American population is limited. The present study aims to recognize the PVs in MMR genes, describe the phenotype in Mexican-Mestizo patients and their relatives, and identify the acceptance rate of cascade testing of relatives at risk. We included 40 carriers of a MMR gene PV and 142 relatives that developed a LS-related neoplasm. Patients’ clinical data, number, and type of malignancies were obtained from their medical records. Amsterdam I-II, Bethesda criteria, and PREMM5® predictive model score were estimated. Available immunohistochemistry (IHC) reports were analyzed. Relatives at risk were determined from index cases pedigrees. The distribution of MMR gene mutations among 40 probands was: MLH1 (67.5 %), MSH2 (22.5 %), MSH6 (7.5 %), and PMS2 (2.5 %). Out of the 182 LS cases, 58 % exhibited the LS phenotype before age 50. The most common tumor was CRC, followed by endometrial cancer in women and gastric cancer in males. We found a 90.0 % concordance between the IHC and germline PV. The most frequent PV in our sample was MLH1 c.676C > T, occurring in 1/6 index cases. All probands disclosed their molecular test result to their family. Out of the 451 asymptomatic relatives at risk, 28.2 % underwent germline testing. Our results highlight the importance of conducting germline genetic studies in LS since it allows the establishment of appropriate cancer screening, risk-reducing measures, and genetic cascade testing among relatives at risk. Interestingly, we observed a significantly higher prevalence of the c.676C > T variant in MLH1, probably a singular characteristic of the Mexican-Mestizo population. New strategies to facilitate accurate communication between index cases and relatives should be implemented to improve the cascade testing acceptance rate.

Occult endometrial cancer in women undergoing hysterectomy for benign indications: a retrospective cohort study in a tertiary hospital in China.

To evaluate the feasibility of further reducing the incidence of occult endometrial cancer in women undergoing hysterectomy for benign gynecological indications. Patients who underwent hysterectomies for presumed benign gynecologic conditions at Peking Union Medical College Hospital were retrospectively identified. Patients with occult endometrial cancer, which was defined as endometrial cancer diagnosed on postoperative histopathology with no preoperative confirmed malignancy, were selected. 24/7558 (0.32%; 95% CI 0.20-0.47%) patients undergoing hysterectomy for benign indications had occult endometrial cancer. Asymptomatic patients with normal endometrial imaging all tended to have favorable pathology. Heavy menstrual bleeding was the most overlooked AUB pattern in the premenopausal group. In the postmenopausal group, all the patients with serous adenocarcinoma or G3 endometrioid adenocarcinoma histology/stage T1b disease/LVSI space invasion had a history of persistent or recurrent PMB ≥ 6months and/or an intracavitary lesion > 20mm in diameter. 3/4 of the samples of the postmenopausal patients did not have adequate endometrium for evaluation. To further reduce the incidence of occult endometrial cancer, physicians should focus on the patient's bleeding pattern and actively implement endometrial sampling whenever indicated. Transvaginal ultrasonography is a valuable preoperative evaluation. Hysteroscopy with directed biopsy is the preferred procedure in postmenopausal patients.

Traits of intrauterine pathology management in the peri- and postmenopausal period

Increasing number of anovulatory cycles in the perimenopause, leading to relative hyperestrogenism, and persistent hypoestrogenism in postmenopause, increase the proliferative activity and change the endometrium morphology. That is associated with higher rates of intrauterine pathology. The prevalence of atypical hyperplasia and endometrial cancer in women of the peri- and postmenopausal periods reaches its maximum values. Therefore, one of the most important concepts of patient’s management is to exclude malignant and precancerous endometrial pathology. Significant hormonal changes leads to important confounders in diagnostic and therapeutic algorithms. It could lead to both hypo- and hyperdiagnosis. The review analyzes the main causes of abnormal uterine bleeding, the features of their clinical manifestation, taking into account probable iatrogenic causes, extrauterus and extragenital sources of spotting. This article reviews the principles of ultrasound examination, considering menstrual cycle phase, duration of menopause, hormone treatment, as well as indications for endometrial biopsy, in case of inconsistency of clinical presentation, ultrasound results, menopausal status and iatrogenic factors. We describe the relevant principles of medical correction, wait-and-see tactics and surgical treatment of abnormal uterine bleeding, both in the presence of organic pathology of the endometrium, and in its absence.

Impact of hormonal contraception on endometrial histology in patients with Lynch syndrome, a retrospective pilot study.

Hormonal contraception (HC) is a well-recognized protection against endometrial cancer (EC) in the general population. It has not been established if this is also applicable to women with Lynch syndrome (LS), a condition associated with a up to 50% lifetime risk of developing EC. The objective of this study was to evaluate if the use of HC influences the incidence of endometrial hyperplasia and EC in women with LS by comparing the histology of annual endometrial biopsies obtained in patients with LS who are using HC versus non-users. This is a retrospective cohort study conducted with endometrial biopsies obtained in women 30 to 50 years of age with LS. The Pearson Chi-square test was performed to compare the prevalence of cancer and hyperplasia in the HC users and in the non-HC users groups. A total of 164 endometrial biopsies obtained among 75 women were suitable for analysis. Among the 86 biopsies obtained in the non-HC group, 81.4% (70/86) were normal. Two cases of endometrial carcinoma (2.3%) and 6 endometrial hyperplasia without atypia were found (7.0%). Among the 78 biopsies performed in patients using HC, 78.2% (61/78) were normal. Three endometrial hyperplasia without atypia (3.8%) and three cases of EC were diagnosed (3.8%). This study suggests that, in women of 30 to 50 years of age with LS, the use of hormonal contraception does not seem to decrease the occurrence of endometrial hyperplasia/carcinoma on annual endometrial histology.

THE INFLUENCE OF DIABETES-ASSOCIATED FACTORS OF ONCOGENESIS ON THE RISK OF BREAST AND ENDOMETRIAL CANCER AND ON THE SURVIVAL OF WOMEN WITH THIS CANCER

Introduction. Patients with type 2 diabetes mellitus (T2D) have an increased risk of cancer of different localizations. Identification and correction of diabetes-associated factors of oncogenesis can be important in cancer prevention.
 The aim of the study. To investigate the influence of diabetes-associated factors of oncogenesis on the formation of the risk of breast cancer (BC) and endometrial cancer (EC), as well as on the survival of women with the indicated localization of cancer, and to develop a method of calculating the predicted risk of BC and EC in women with T2D.
 Materials and methods. The study includes the results of a retrospective epidemiological analysis of cancer cases in patients, residents of Ivano-Frankivsk region with T2D during 2012-2016, with an analysis of 5-year survival of patients. Statistical processing of the results was conducted using STATISTIKA-12 (StatSoft Inc., USA). The impact of the pathogenetic factors of T2D on the development of BC and EC was evaluated through multifactorial analysis and ROC-analysis in the Medcalc v.19.1.6 program. The coefficient of predicted cancer risk was determined using mathematical modelling and a logistic regression equation. Kaplan-Meier cumulative survival analysis and Cox-Mantel Test were used to assess patient survival.
 Results. BC and EC were most often diagnosed in women of postmenopausal age, with obesity, with a duration of T2D > 5 years, on combined antidiabetic therapy. Among women with BC, who take secretagogues 67% had obesity and 24% were overweight, with EC – 54% and 27% respectively. A new method to calculate the predicted risk of BC and EC (Y) in women with T2D has been introduced. The accuracy of the mathematical model for calculating the Y index is 76.24%. It was proved that coefficient Y increases in women with obesity (p<0.001), duration of T2D > 5 years (p<0.001), on combined therapy with non-secretagogues and secretagogues (p<0.05). It was found that T2D increases the risk of death within 1 year in women with both types of cancer (p<0.05). A worse 5-year survival rate was found in women with EC stage I treated with drugs that increase blood insulin levels (p<0.05), as well as in women with EC stage II with HbA1c > 8.0% (p<0.05).
 Conclusions. Obesity, duration of diabetes > 5 years, and use of secretagogues in obesity increase the risk of breast and endometrial cancer in women with T2D. The use of antidiabetic drugs that contribute to iatrogenic hyperinsulinemia may negatively affect survival in obese women with breast and endometrial cancer, both by increasing the risk of cardiovascular events and by hyperactivating insulin signaling. Decompensation of diabetes reduces the 5-year survival of patients with breast cancer and endometrial cancer. Detection of a predicted high-grade cancer risk (p = 0.7-1.0) may be an indication for correction of factors of oncogenesis and cancer screening in women with T2D.

Silent Threats Unveiled: Navigating the Landscape Endometrial Cancer in Women Over 50 - A Comprehensive Analysis of Post-Menopausal Bleeding as a Crucial Diagnostic Indicator

Background: Endometrial cancer, with a global incidence of 9 per 100,000 women and a 1% lifetime risk, predominantly affects women aged >50 years and commonly manifests as post-menopausal bleeding (PMB). Timely referral for further investigation is imperative in cases of PMB. Objective: This study aimed to determine the frequency of endometrial cancer in females with abnormal uterine bleeding (AUB) and compare this frequency between premenopausal and postmenopausal women presenting with AUB. Study Design: Descriptive cross-sectional study. Settings: Department of Obstetrics & Gynecology, Independent University Hospital, Faisalabad Pakistan. Duration: Six months from December 15, 2022 to June 15, 2023. Methods: This study aimed to assess endometrial samples from 415 females over. Participants meeting inclusion criteria were enrolled from the Department's outpatient department, providing informed consent and demographic details. Endometrial sampling using Pipelle or D&C under general anesthesia was performed, and subsequent histopathology assessments in the hospital's pathology laboratory categorized findings into premenopausal and postmenopausal groups for comparative analysis. The study, initiated after ERC approval, spanned. Results: Out of 415 cases, 61.45% (n=255) were aged 30-50 years, while 38.55% (n=160) were aged 51-70 years, with a mean age of 48.52±7.02 years. The frequency of endometrial cancer in females with AUB was 6.51% (n=27). Comparing premenopausal (4.46%, n=10) to postmenopausal (8.90%, n=17) females with endometrial cancer, the p value was 0.06. Conclusion: While the overall frequency of endometrial cancer in females with AUB requires attention, this study emphasizes that the frequency is significantly lower in premenopausal compared to postmenopausal females presenting with AUB.

A Complete Overview of the Polycystic Ovarian Syndrome with Recent Advancement in Clinical Trial

Background: Polycystic ovarian syndrome (PCOS) has emerged as one of the most common endocrine and metabolic disorders seen in women of childbearing age throughout the whole world. The complex pathophysiology, different diagnostic criteria, and various manifestations attached to several environmental factors, including lifestyle influences, have made it one of the most difficult disorders to treat in recent times. In addition, inadequate knowledge among patients and a lack of dedicated approved medications have only enhanced the difficulties in treating such a heterogeneous disorder. Objective: The main objective of this review-type paper is to provide a detailed overview of PCOS along with the current concept of a clinical stance in this complex multigenic disorder. Method: The following databases were used for literature searches: PubMed, Frontiers, Science Direct, Springer, Wiley, and MDPI. For the purpose of finding pertinent articles and contents, the keywords “PCOS; hirsutism; psychological burden; obesity” and others of a similar nature were utilized. Conclusion: PCOS is a complicated hormonal, metabolic, and psychological condition with many different clinical manifestations. It is among the most prevalent causes of infertility. Before considering any medication choices, lifestyle modifications should be considered the primary therapeutic prescription for PCOS-related infertility. According to recent studies, PCOS does not affect the risk of ovarian or breast cancer, but it does raise the risk of endometrial cancer in women of all ages. These results suggest that PCOS may increase the risk of gynaecological cancer morbidity. The following stage is ovulation stimulation, which is best accomplished with letrozole and is followed by clomiphene citrate. Women who had not responded to the first-line oral ovulatory medicine were given gonadotropins as a backup. Early detection of girls with a high propensity to develop PCOS will be made possible by a comprehensive knowledge of the condition's etiology. Adolescent PCOS will be better managed overall, related comorbidities will be prevented, and quality of life will increase with customized therapeutic approaches.

Concurrent Endometrial Cancer in Women with Atypical Endometrial Hyperplasia: What Is the Predictive Value of Patient Characteristics?

The rate of concurrent endometrial cancer (EC) in atypical endometrial hyperplasia (AEH) can be as high as 40%. Some patient characteristics showed associations with this occurrence. However, their real predictive power with related validation has yet to be discovered. The present study aimed to assess the performance of various models based on patient characteristics in predicting EC in women with AEH. This is a retrospective multi-institutional study including women with AEH undergoing definitive surgery. The women were divided according to the final histology (EC vs. no-EC). The available cases were divided into a training and validation set. Using k-fold cross-validation, we built many predictive models, including regressions and artificial neural networks (ANN). A total of 193/629 women (30.7%) showed EC at hysterectomy. A total of 26/193 (13.4%) women showed high-risk EC. Regression and ANN models showed a prediction performance with a mean area under the curve of 0.65 and 0.75 on the validation set, respectively. Among the best prediction models, the most recurrent patient characteristics were age, body mass index, Lynch syndrome, diabetes, and previous breast cancer. None of these independent variables showed associations with high-risk diseases in women with EC. Patient characteristics did not show satisfactory performance in predicting EC in AEH. Risk stratification in AEH based mainly on patient characteristics may be clinically unsuitable.

Surface-enhanced Raman spectroscopy in women with benign and malignant endometrial diseases

Background. This study aimed to enhance early detection of endometrial cancer in women and distinguish benign conditions from endometrial cancer using surface-enhanced Raman scattering (SERS) analysis of blood plasma, thus increasing diagnostic efficacy.
 Materials and methods. The study of blood plasma from 95 female patients aged 22–79 years was performed. The patients were divided into four groups: group 1 included 29 women with endometrial adenocarcinoma, group 2 included 31 patients with endometrial polyp, group 3 included 10 women with endometrial hyperplasia, and the comparison group consisted of 25 healthy women. Blood plasma was analyzed via SERS, with three Raman spectra recorded per sample. Spectral measurements of the SERS substrate were assessed using dried samples on an experimental bench equipped with the spectrometric system RL785 (LLC “Foton-Bio”, Russia), incorporating a CCD detector, laser radiation source with a wavelength of 785 nm, and ADF U300 microscope (ADF, China). A silver substrate composed of dried silver colloid was used to demonstrate the enhancement effect on the Raman signal from the surface of the blood plasma.
 Results. Spectral and specific features that distinguish adenocarcinoma, polyps, and endometrial hyperplasia were identified and evaluated. Spectral and quantitative differences specific to each condition, which are crucial for the differential diagnosis of pathologic tissues, were also identified. The accuracy rates of the optical diagnostics in distinguishing endometrial adenocarcinoma from the control group and endometrial hyperplasia were 87% and 85%, respectively, for the calibration and verification spectral sets (where the sensitivity and specificity were 66% and 92% for the spectral verification set, respectively). The accuracy rates of distinguishing control from endometrial hyperplasia and endometrial adenocarcinoma were 86% and 85%, respectively, and the accuracy of distinguishing endometrial hyperplasia from control and endometrial adenocarcinoma was 81% for the calibration and verification sets of spectra. In addition, the study demonstrated improved accuracy in differentiating adenocarcinoma from hyperplasia, including polyps. The accuracy rate was 93% in the calibration set of spectra, with sensitivity and specificity of 96% and 90%, whereas in the validation set, it was 91%, with sensitivity and specificity of 93% and 88%, respectively.
 Conclusions. The study demonstrated the potential use of SERS for differentiating expression patterns in endometrial cancer from those in benign conditions.

Short-Term Outcome of Robotic versus Laparoscopic Hysterectomy for Endometrial Cancer in Women with Diabetes: Analysis of the US Nationwide Inpatient Sample.

This study investigated short-term outcomes of robotic versus laparoscopic hysterectomy for endometrial cancer (EC) in women with diabetes. We extracted the data of hospitalized females aged ≥18 years who were diagnosed with EC and diabetes and underwent robotic or laparoscopic hysterectomy from the US Nationwide Inpatient Sample (NIS) 2005-2018. Associations between study variables and in-hospital outcomes, including complications, unfavorable discharge, length of stay (LOS), and hospital costs, were examined using logistic regression. A total of 5745 women (representing 28,176 women in the US) were included. Multivariable analysis revealed that robotic surgery was significantly associated with a decreased risk of unfavorable discharge (adjusted odds ratio [aOR] = 0.63, 95% confidence interval [CI]: 0.46, 0.85) than pure laparoscopic surgery. Women who underwent robotic surgery had a significantly shorter LOS (0.46 fewer days, 95% CI: -0.57, -0.35) but higher total hospital costs (6129.93 greater USD; 95% CI: 4448.74, 7811.12). Compared with pure laparoscopic surgery, robotic hysterectomy was associated with less unfavorable discharge among women aged ≥60 years (aOR = 0.60, 95% CI: 0.44, 0.80). For US women with EC and diabetes, robotic hysterectomy is associated with shorter LOS, decreased risk of unfavorable discharge, especially among older patients, and higher total costs than laparoscopic surgery.

Deciphering the Role of Insulin-Like Growth Factor 1 in Endometrial Cancer in Patients With Polycystic Ovary Syndrome: Protocol for a Methodological Approach Using Cell Culture Experiments.

Endometrial cancer (EC) is the most common gynecological cancer in women globally. It is linked to increasing obesity rates and longer life spans. The molecular mechanisms leading to EC are unclear; however, women with polycystic ovary syndrome (PCOS) have a 3- to 5-fold increased EC risk. According to a pilot study conducted in the United Kingdom, insulin-like growth factor-1 (IGF-1) gene and protein were raised in the endometrium and blood of women with EC and PCOS, compared with those without PCOS (controls). Therefore, raised serum IGF-1 levels may contribute to an increased EC risk in women with PCOS, but it is necessary to test this hypothesis since not all studies have demonstrated this association. This study aims to investigate the role of IGF-1 in mediating EC risk in PCOS. This will be achieved by evaluating the proliferative effects of PCOS serum, IGF-1, and IGF-1 antagonist on human endometrial cancer 1-A and 1-B cell lines, with a comparison to controls (using serum from women without PCOS and cell culture media). The study will also identify differentially expressed genes and pathways activated by various treatments. We intend to recruit 20 women with PCOS and 20 women without PCOS for this cross-sectional study. All experiments will be carried out 4 times to ensure consistency. We will perform transcriptomic and phosphoproteomic profiling to identify differentially expressed genes and phosphoproteins between different treatments using RNA sequencing and phosphoproteomics. We will also perform bioinformatics pathway analysis to identify whether any unique collection of genes or phosphoproteins explains increased EC risk in PCOS. The primary outcome measure will be the cell proliferation (growth) difference measured by cell index values. Our protocol stands out due to its unique approach; no previous study has used this approach to investigate the oncogenic effect of serum from women with PCOS. Additionally, no previous study has considered the differential mutations of genes related to the insulin signaling pathway across various types of human EC cell lines and the potential impact of these variations on their experimental findings. Participants are currently being recruited. It is expected that preliminary findings suitable for analysis and publication will be available by the summer of 2024. Although we currently do not have any results to report, sharing our protocol at this stage will aid in research collaboration, provide an opportunity for early feedback, and help reduce duplication of effort by other research groups. The findings of our study will have broader implications. A deeper understanding of the mechanisms underlying the regulation of the IGF system in PCOS and EC will improve our ability to develop effective treatment modalities for EC and will be a vital step toward reducing EC in women globally. DERR1-10.2196/48127.

SAT370 Economic Burden of Endometrial Cancer Associated with Polycystic Ovary Syndrome

Abstract Disclosure: L.A. Pace: None. D. Markovic: None. R.P. Buyalos: Employee; Self; Fertility and Surgical Associates of California. F. Bril: None. R. Azziz: Advisory Board Member; Self; Arora Forge. Consulting Fee; Self; Rani Therapeutics, Spruce Biosciences, Fortress Biotech, Core Access Surgical Technologies. Grant Recipient; Self; Foundation for Research and Education Excellence, Ferring Pharmaceuticals. Stock Owner; Self; Martin Imaging. Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive aged females, affecting approximately 6 million U.S. women. Endometrial cancer, in turn, is the most common gynecological malignancy and the fourth most common cancer overall in female patients. Objectives: To assess the excess economic burden associated with endometrial cancer in women with PCOS. Method: Using PRISMA guidelines for systematic review, we searched PubMed, Web of Science, Scopuse, and Embase for all studies on endometrial cancer in patients with known PCOS. Excluded studies were reviews and case reports, those not conducted in human subjects, without controls, without full text available, or reporting solely on diseases other than PCOS. Selected studies were assessed for quality using the Newcastle-Ottawa Scale. Meta-analysis was performed using the DerSimonian-Laird random effects model to assess the pooled risk ratio (RR) for the association between PCOS and endometrial cancer, then calculation of the excess cost was assessed in U.S. dollars (USD), adjusted for inflation using a medical care inflation calculator. Result: We screened 98 studies by title and abstract, 32 titles in full text, and included 11 articles. Pooled RR was 2.90 (95% CI 1.57-5.37), p=0.0196. In the U.S., overall prevalence of endometrial cancer in patients with PCOS is 0.409%, compared with baseline estimated five-year prevalence (2014-2019) of endometrial cancer in all women of 0.141%, or 235,596 cases. The excess prevalence of endometrial cancer in women with PCOS is therefore 0.2679%, or approximately 361 women. Direct healthcare costs associated with endometrial cancer per patient per year were estimated to be $8,597, when adjusted for inflation to 2022 costs. Therefore, the excess cost of endometrial cancer related to PCOS is estimated at 361 x $8,597 = $3.1 million per year in 2022 USD. Conclusion: In 2022 USD, the excess annual healthcare cost for endometrial cancer care in patients with PCOS exceeds $3 million per year. While the overlap between the risk factors and pathophysiologic underpinnings of both conditions is well-known, PCOS is not always directly addressed as a risk factor for endometrial cancer. Given the findings of this meta-analysis, taken in combination with previously collected data estimating the annual healthcare costs associated with PCOS diagnosis and treatment alone, to exceed $2 billion, we advocate for and increased focus in the global health, policy, and scientific communities to better address this condition and its sequelae. Funding: Foundation for Research and Education Excellence Presentation Date: Saturday, June 17, 2023

К ВОПРОСУ О РИСКАХ МАЛИГНИЗАЦИИ ЭНДОМЕТРИОМ ЯИЧНИКА

Introduction. Endometriosis is a widespread gynecological disease. In the last few years, new data have been accumulating confirming that endometriosis leads to an increased risk of malignant neoplasms of the ovaries, endometrium, breast and thyroid gland. The most commonly found form of endometriosis is endometrioma. Objective: to analyze epidemiological and genetic studies of the risks of neoplastic transformation of ovarian endometriomas based on search results in electronic resources MEDLINE, EMBASE, Elibrary from 2012 to 2023. Results. Epidemiological and genetic studies have proven the risk of malignancy of endometriosis with the development of ovarian cancer related to endometriosis. Studies confirmed, that two histotypes of epithelial ovarian cancer, such as clear-cell and endometrioid cancer, most closely related to endometriosis. Genome-wide association studies (GWAS) have confirmed the risk of endometrial cancer in women with endometriosis, which was shown earlier than epidemiological studies. Finding the genes and pathways underlying these complex diseases is an essential step toward developing better diagnostic and therapeutic tools. Conclusion. The review presents epidemiological and genetic evidence of the risks of ovarian cancer and endometrial cancer in women with endometriosis.

Pregnancy complications and endometrial cancer in women with polycystic ovarian syndrome: a Korean National Health Insurance Service study

ObjectivePolycystic ovarian syndrome is associated with diverse pregnancy related complications and endometrial cancer. However, research on the relationship between pregnancy complications and endometrial cancer in women with polycystic ovarian syndrome...

Conservative treatment of endometrial cancer in women of reproductive age (Review).

Endometrial cancer is the fifth most common female cancer worldwide and the third leading female cancer in the Western world. The marked surge in endometrial cancer incidence is alarming. The aim of the present review is to focus on endometrial cancer affecting young women of reproductive age. Surgery, namely abdominal or laparoscopic hysterectomy, with or without salpingo-oophorectomy, and sentinel lymph node detection has become the standard surgical strategy for early stage endometrioid endometrial cancer. However, premenopausal women might want to preserve their fertility, especially if they are nulliparous or have not reached their desired number of children at the time of diagnosis. Conservative, uterus-sparing treatment, based on progestin products, may be an advantageous option for patients meeting the necessary criteria. Potential candidates have to be committed to following a rigorous protocol of treatment, investigations and follow-up. The evidence in favor of this approach, although limited, is encouraging and patients who have achieved a histologically documented disease complete remission could attempt to conceive spontaneously or with the immediate use of assisted reproductive technology techniques. The risk of partial or negative response to progestin treatment or cancer recurrence is well documented, thus patients have to be aware of the possible need for interruption of conservative treatment and hysterectomy.