Diagnosis Of Endometrial Cancer Research Articles

Clinical characteristics of patients with endometrial cancer and modern diagnosis methods

Clinical characteristics of patients with endometrial cancer and modern diagnosis methods

Abstract PO-201: African ancestry predicts serous and copy number high endometrial cancer

Abstract Introduction: Endometrial cancer (EC) is the leading gynecologic malignancy in the United States. Histologic classification is binary, with type I, low-grade tumors being exclusively endometrioid and type II, high-grade tumors inclusive of aggressive histologies like serous carcinoma. Molecular classification defines EC as POLE ultra-mutated, microsatellite instability (MSI), copy number low (CNL) and copy number high (CNH). Relative to White women, Black women have a higher risk of serous/CNH EC with worse overall survival. We aimed to understand whether self-identified race and genetic ancestry are associated with the probability of developing serous/CNH tumors among women diagnosed with EC. Methods: We reviewed tumor genomic data from The Cancer Genome Atlas (TCGA) and The Cancer Genetic Ancestry Atlas (TCGAA) under the project Uterine Corpus Endometrial Carcinoma. We merged both datasets matching the Patient ID and extracted age of diagnosis, histology, molecular classification, self-identified race, genomically-assigned race by EIGENSTRAT, and percentage of African, European, Asian, and Native American ancestry. We used chi-square or one-way ANOVA to test for associations to Serous/CNH diagnosis. Controlling for age, we used multivariate logistic regression to determine the odds of diagnosis with serous or CNH EC. Results: We identified 568 women with EC, including 115 (20%) self-identified Black, 417 (73%) White, and 23 (4%) Asian. Significant differences in mean age at diagnosis (p<0.01), self-identified race (p<0.01), and genomically-assigned race (p<0.01) were present between women with endometrioid and serous histologies. Self-identified race and genomically-assigned race were both significantly associated with molecular subtype of cancer (p<0.01). A greater percentage of African Ancestry was seen in CNH vs CNL (27% vs 11%, p<0.01) and CNH vs MSI (27% vs 15%, p<0.001). In logistic regression, self-identified Black women had higher probability of diagnosis with serous EC (OR=2.129, CI [1.273–3.561], p<0.01) and CNH tumors (OR=2.846, CI [1.759–4.604], p<0.001) compared to self-identified White women. Relative to women characterized as European American (≥48% European Ancestry), African Americans (≥35% African ancestry) had greater odds of serous EC diagnosis (OR=2.289, CI [1.376–3.806], p<0.01) and CNH molecular type (OR=2.839 CI [1.760–4.579], p<0.01). For every 1% increase in African ancestry there was 1% increase in the probability of diagnosis with serous EC (CI [1.004–1.017], p<0.01) and 1.4% increase on the likelihood of diagnosis with CNH EC (CI [1.008–1.020], p<0.01), with this percentage increasing directly proportional. Conclusion: Our findings suggest that African ancestry is associated with an increased odds for both high-grade EC histology and molecular EC classification. Self-identified race and genomically-assigned race demonstrate similar associations with aggressive disease. Further characterization of the molecular drivers of EC, with consideration of environmental factors and how they may impact risk, is warranted. Citation Format: Alex P. Sanchez-Covarrubias, Angel D. Tabuyo-Martin, Caiden J. Walter, Alexandra Diaz, Sophia H.L. George, Matthew P. Schlumbrecht. African ancestry predicts serous and copy number high endometrial cancer [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-201.

Evaluation of Inferior Mesenteric Superior Lymph Node Metastasis in Early-Stage Endometrium Cancer and Its Clinical Significance

Endometrial cancer is the fourth most common type of cancer in women cancers. In the light of projections, approximately 11,000 deaths occur annually in the USA alone. Lymph node metastasis is the most important prognostic factor in endometrial cancer. The aim of this study is to investigate the clinical and histopathological risk factors affecting lymph ode involvement. The study included 30 randomly selected women from external centers who applied to our clinic with a preliminary diagnosis of endometrial cancer and were diagnosed with endometrial cancer in our clinic. The study group was divided into two groups as stage I (early stage) and stage II and above (advanced stage) according to the stages. Total abdominal hysterectomy (Type II), bilateral salpingo-oophorectomy, paraaortic lymph node dissection from the pelvic and IMA to the level of the left renal vein, omentectomy, and peritoneal cytology sampling were performed on each of the endometrial cancer participants. The mean number of lymph node involvement in 30 patients in the study group was 45.9±15.1. The mean number of pelvic lymph nodes involved was 32.1±10.1, while the mean number of paraaortic lymph nodes involved was 13.9±6.9. As a result of the examinations, the highest number of Stage Ia was found. The frequency of endometrial adenocarcinoma was 80% and it was seen in 24 people. The mean tumor size, myometrial thickness, and depth of invasion of the patients were 2.97(±1.6), 1.57(±0.6), and 0.7(±0.6), respectively. With positive sub-IMA lymph node involvement, lymph node positivity was also detected in the area extending from the IMA to the level of the renal vein. It has been shown that the non-endomethroid tumor type detected in this group, myometrial invasion of more than 50%, grade 3 tumor and the presence of lymphovascular invasion affect lymph node involvement above the IMA.

Endometrial cancer prognosis in women with endometriosis and adenomyosis: A retrospective nationwide cohort study of 40 840 women.

We aim to compare endometrial cancer survival in women with or without histological proven endometriosis or adenomyosis. We identified all women with endometrial cancer between 1990 and 2015 from the Netherlands Cancer Registry (NCR). Data were linked to the Dutch pathology database (PALGA) to select all women with histological proven endometriosis/adenomyosis. Overall survival was compared between women with endometrial cancer with or without endometriosis/adenomyosis. We used multivariable Cox proportional hazard analysis to estimate hazard ratios (HRs). We included 1701 women with endometrial cancer and endometriosis/adenomyosis, of whom 1236 (72.7%) women had adenomyosis, 320 (18.8%) had endometriosis and 145 (8.5%) had both. We compared these women to 39 139 women with endometrial cancer without endometriosis/adenomyosis. Women in the combined endometriosis/adenomyosis cohort were younger at endometrial cancer diagnosis, had earlier disease stage, more often had endometrioid endometrial cancer and low grade tumors. The 5‐year survival rate in the combined endometriosis/adenomyosis cohort was 84.8% (95% CI 84.6‐88.1) and 71.6% (95% CI 71.1‐72.0) in the nonendometriosis/adenomyosis cohort. Univariable analysis resulted in a crude HR of 0.63 (95% CI 0.59‐0.69). Significant confounding factors were age, stage, cancer subtype, histological grading, surgery and chemotherapy rate. Correction for these confounders resulted in a HR of 0.98 (95% CI 0.90‐1.06). Including endometriosis/adenomyosis status as a categorical factor resulted in similar HRs. In conclusion, women with endometrial cancer and histologically proven endometriosis/adenomyosis have a better overall survival when compared to women with endometrial cancer without endometriosis/adenomyosis. This better survival was correlated to stage, grade, age and histological subtype, but not to the presence of endometriosis/adenomyosis.

Does an Endometrial Cancer Diagnosis among Asymptomatic Patients Improve Prognosis?

Simple SummaryEndometrial cancer is common malignancy with an excellent prognosis due to its early symptoms—abnormal bleeding. It is still common in some countries to provide a biopsy in asymptomatic patients based on ultrasound findings; even though, it is not supported by the European guidelines. The aim of our study was to find out if there is a prognostic difference among symptomatic and bleeding-free patients with similar clinical histological characteristics.Background: Endometrial cancer is the most common gynecological malignancy in developed countries with no screening available. There is still a tendency to provide invasive bioptic verification in asymptomatic women with abnormal ultrasound findings to diagnose carcinoma in a preclinical phase; even though, it is not supported by European guidelines. Our goal was to determine DFS (disease-free survival), OS (overall survival), and DSS (disease-specific survival) differences between symptom-free and symptomatic (bleeding, or spotting) endometrial cancer patients with similar stage and tumor/clinical characteristics. Methods: All of our patients with endometrial cancer following surgical treatment between 2006 and 2019 were assessed, evaluating risk factors for recurrence and death while focusing on bleeding using univariable and multivariable analysis. Results: 625 patients meeting the inclusion criteria were divided into asymptomatic (n = 144, 23%) and symptomatic (n = 481, 77%) groups. The median follow-up was 3.6 years. Using univariable analysis, symptomatic patients had a three times higher risk of recurrence (HR 3.1 (95% Cl 1.24–7.77), p = 0.016). OS (HR 1.35 (0.84–2.19), p = 0.219) and DSS (HR 1.66 (0.64–4.28), p = 0.3) were slightly worse without reaching statistical significance. In our multivariable analysis, symptomatology was deemed completely insignificant in all monitored parameters (DFS: HR 2.03 (0.79–5.24), p = 0.144; OS: HR 0.72 (0.43–1.21), p = 0.216). Conclusions: The symptomatic endometrial cancer patients risk factor of earlier recurrence and death is insignificantly higher when compared with the asymptomatic cohort. However, multivariable analysis verifies that prognosis worsens with other clinically relevant parameters, not by symptomatology itself. In terms of survival outcome in EC patients, we recognized symptomatology as a non-significant marker for the patient’s prognosis.

The role of adiposity in endometrioid endometrial cancer

The incidence of endometrial cancer (EC) is estimated to increase by 1–2% annually. More than half of all endometrioid EC diagnoses are currently attributable to obesity, which is an independent risk factor for this cancer. Multiple epidemiologic studies have demonstrated that obesity significantly increase the risk of several types of cancer, however, mechanisms by which obesity contribute to EC progression remain elusive. The objective of this study is to compare the effects of adiposity on endometrioid endometrial cancer cells in a paracrine, endocrine and intratumoral environment both invitro and in vivo.

PREVENTION OF ENDOMETRIAL CANCER

Endometrial carcinoma is a malignancy originating from the epithelial cells lining the uterine cavity. 1,3 Currently, endometrial carcinoma is often found in gynecological malignancies. Endometrial carcinoma is the sixth leading cause of death from malignancy in women. In Indonesia, endometrial cancer ranks third for genital cancer after cervical (cervical) and ovarian cancer. An endometrial biopsy is done to diagnose and evaluate abnormal intrauterine bleeding, t. However, in patients who cannot undergo an endometrial biopsy because of cervical stenosis or symptoms persist despite normal biopsy results, dilatation and curettage may be performed under anesthesia. Dilatation and curettage procedures are currently the gold standard for the diagnosis of endometrial cancer.2 Microscopic examination of endometrial biopsy and endocervical curettage can usually confirm the diagnosis of endometrioid or mucinous adenocarcinoma but rarely can be associated with the initial lesion of cervical adenocarcinoma in situ or atypical hyperplasia of the endometrium. The prognosis of patients with this type is poor and has a lower survival rate than patients with type 1. In addition, in some types of type 2 endometrial adenocarcinoma found an increase in molecules that are generally found in type 1, this indicates that type 2 endometrial adenocarcinoma can occur as a worsening. from the pre-existing type 1. 4 The risk of endometrial cancer is strongly associated with family history, Therefore, screening is needed as early as possible.6

Pharmacological Treatment of Advanced, Persistent or Metastatic Endometrial Cancer: State of the Art and Perspectives of Clinical Research for the Special Issue "Diagnosis and Management of Endometrial Cancer".

Simple SummaryPatients with metastatic or recurrent endometrial cancer (EC) not suitable for surgery and/or radiotherapy are candidates for pharmacological treatment with unsatisfactory clinical outcomes. The combination of carboplatin + paclitaxel is the standard first-line chemotherapy, whereas hormonal therapy is sometimes used in selected patients with slow-growing steroid receptor-positive EC. The combination of endocrine therapy with mTOR inhibitors or cyclin-dependent kinase 4/6 inhibitors is currently under evaluation. Immune checkpoint inhibitors, and especially pembrolizumab and dostarlimab, have achieved an objective response in 27–47% of highly pretreated patients with microsatellite instability-high/mismatch repair (MMR)-deficient EC.Patients with metastatic or recurrent endometrial cancer (EC) not suitable for surgery and/or radiotherapy are candidates for pharmacological treatment frequently with unsatisfactory clinical outcomes. The purpose of this paper was to review the results obtained with chemotherapy, hormonal therapy, biological agents and immune checkpoint inhibitors in this clinical setting. The combination of carboplatin (CBDCA) + paclitaxel (PTX) is the standard first-line chemotherapy capable of achieving objective response rates (ORRs) of 43–62%, a median progression-free survival (PFS) of 5.3–15 months and a median overall survival (OS) of 13.2–37.0 months, respectively, whereas hormonal therapy is sometimes used in selected patients with slow-growing steroid receptor-positive EC. The combination of endocrine therapy with m-TOR inhibitors or cyclin-dependent kinase 4/6 inhibitors is currently under evaluation. Disappointing ORRs have been associated with epidermal growth factor receptor (EGFR) inhibitors, HER-2 inhibitors and multi-tyrosine kinase inhibitors used as single agents, and clinical trials evaluating the addition of bevacizumab to CBDCA + PTX have reported conflicting results. Immune checkpoint inhibitors, and especially pembrolizumab and dostarlimab, have achieved an objective response in 27–47% of highly pretreated patients with microsatellite instability-high (MSI-H)/mismatch repair (MMR)-deficient (-d) EC. In a recent study, the combination of lenvatinib + pembrolizumab produced a 24-week response rate of 38% in patients with highly pretreated EC, ranging from 64% in patients with MSI-H/MMR-d to 36% in those with microsatellite stable/MMR-proficient tumors. Four trials are currently investigating the addition of immune checkpoint inhibitors to PTX + CBDCA in primary advanced or recurrent EC, and two trials are comparing pembrolizumab + lenvatinib versus either CBDCA + PTX as a first-line treatment of advanced or recurrent EC or versus single-agent chemotherapy in advanced, recurrent or metastatic EC after one prior platinum-based chemotherapy.

Endometrial Cancer: Genetic, Metabolic Characteristics, Therapeutic Strategies and Nanomedicine.

Endometrial cancer is the fourth most common malignancy in female population worldwide. It was estimated that 65,620 new cases and 12.590 subsequent deaths occurred in 2020 in the United States. Patients with type II and advanced endometrial cancer do not respond well to the current treatments. Therefore, endometrial cancer should be better understood in order to develop more effective treatments. To provide an overview of genetic, metabolic characteristics, therapeutic strategies and current application of nanotechnology surrounding endometrial cancer. Relevant articles were retrieved from Pubmed and were systematically reviewed. Hypoxia inducible factor-1 and Von Hippel-Lindau factor participated in oncogenesis and progression of endometrial cancer and Nrf2 was associated with oncogenesis. Various genetic alterations were found in endometrial cancer. Examining the abnormal X chromosome inactivation may help in the diagnosis of endometrial cancer and its precancerous lesions. Some absent tumor suppressor genes, activated oncogenes were revealed by the genetically modified mouse models. Disorders in glucose and lipid metabolism were found in endometrial cancer. Current therapeutic strategies focused on the HIF-1α pathway, the mTOR pathway as well as the immunotherapy. Nanotechnology showed great potential in endometrial cancer's early diagnosis, metastasis determination and treatment. Endometrial cancer has been understood in various aspects but the underlying mechanisms still remain relatively unknown, which might be the source of novel diagnostic, prognostic and therapeutic targets. Nanomedicine in endometrial cancer is poorly studied but the current researches showed great results in treating endometrial cancer. It needs further researching.

The predictive and prognostic value of CA 125 in endometrial cancer

Endometrial cancer is the most common malignant tumour of the female genital tract. It affects mainly older women, with postmenopausal bleeding as the primary symptom. The diagnosis of endometrial cancer is confirmed by histological evaluation of tissue specimens and described as either type I or type II. Treatment includes surgery (hysterectomy, adnexectomy and dissection of pelvic and paraaortic lymph nodes), radiotherapy, chemotherapy and hormonal therapy. Preoperative serum CA 125 (Cancer Antigen 125 or Carbohydrate Antigen 125) concentrations are correlated with depth of myometrial invasion, lymph node metastases, positive peritoneal cytology and invasion of the lymphovascular space, and can assist in making decisions about the extent of surgery. Preoperative CA 125 levels have prognostic value; postoperative levels serve as a predictor of early recurrence. Elevated serum CA 125 is linked not only with endometrial cancer, but also with several benign and malignant conditions, including ovarian cancer. Other tumour markers (e.g., CA 15–3, CA 19–9) and a promising new marker human epididymis protein 4 (HE4) can also be used for managing patients with endometrial cancer.

Diagnostic Accuracy of Liquid Biopsy in Endometrial Cancer.

Simple SummaryThe number of endometrial cancer (EC) cases is constantly growing. However, the current diagnostic approach is still rather imprecise, leaving 1/3 of patients temporarily undiagnosed. Moreover, final diagnosis is made after the surgery. That mean the histology of tumor, which influences scope of resection, is uncertain during procedure. This results in over- and undertreatment of EC patients. Those diagnostic problems might be solved by liquid biopsy—a new, minimally invasive method to obtain tumor biomarkers. Therefore, this study aimed to evaluate the usefulness of information obtained from liquid biopsy components (tumor educated platelets and circulating tumor DNA) coupled with random forest algorithm and deep neural networks to diagnose EC patients and evaluate tumor histology preoperatively.Background: Liquid biopsy is a minimally invasive collection of a patient body fluid sample. In oncology, they offer several advantages compared to traditional tissue biopsies. However, the potential of this method in endometrial cancer (EC) remains poorly explored. We studied the utility of tumor educated platelets (TEPs) and circulating tumor DNA (ctDNA) for preoperative EC diagnosis, including histology determination. Methods: TEPs from 295 subjects (53 EC patients, 38 patients with benign gynecologic conditions, and 204 healthy women) were RNA-sequenced. DNA sequencing data were obtained for 519 primary tumor tissues and 16 plasma samples. Artificial intelligence was applied to sample classification. Results: Platelet-dedicated classifier yielded AUC of 97.5% in the test set when discriminating between healthy subjects and cancer patients. However, the discrimination between endometrial cancer and benign gynecologic conditions was more challenging, with AUC of 84.1%. ctDNA-dedicated classifier discriminated primary tumor tissue samples with AUC of 96% and ctDNA blood samples with AUC of 69.8%. Conclusions: Liquid biopsies show potential in EC diagnosis. Both TEPs and ctDNA profiles coupled with artificial intelligence constitute a source of useful information. Further work involving more cases is warranted.

The wait time to primary surgery in endometrial cancer – impact on survival and predictive factors: a population-based SweGCG study

Background Poor survival rates in different cancer types are sometimes blamed on diagnostic and treatment delays, and it has been suggested that such delays might be related to sociodemographic factors such as education and ethnicity. We examined associations of the wait time from diagnosis to surgery and survival in endometrial cancer (EC) and explored patient and tumour factors influencing the wait time. Material and methods In this historical population-based cohort study, The Swedish Quality Registry for Gynaecologic Cancer (SQRGC) was used to identify EC patients who underwent primary surgery between 2010 and 2018. Factors associated with a wait time > 32 d were analysed with logistic regression. The 32-d time point was defined in accordance with the Swedish Standardisation Cancer Care programme. Adjusted Poisson regression analyses were used to analyse excess mortality rate ratio (EMRR). Results Out of 7366 women, 5535 waited > 32 d for surgery and 1098 > 70 d. The overall median wait time was 44 d. The factors most strongly associated with a wait time > 32 d were surgery at a university hospital (adjusted odds ratio [OR] 1.34, 95% confidence interval [CI] 1.08–1.66) followed by country of birth (OR 1.31, 95% CI 1.10–1.55) and year of diagnosis. There were no associations between wait time and histology or age. A wait time < 15 d was associated with higher mortality (adjusted EMRR 2.29,95% CI 1.36–3.84) whereas no negative survival impact was seen with a wait time of 70 d. Age, tumour stage, histology and risk group were highly associated with survival, whereas education, country of origin and hospital level did not have any impact on survival. Conclusions Surgery within the first two weeks after EC diagnosis was associated with worsened survival. A prolonged wait time did not seem to have any significant adverse effect on prognosis. Highlights Surgery within the first two weeks after diagnosis of endometrial cancer (EC) was associated with poorer survival. A prolonged wait time to surgery did not worsen prognosis. Delay in time to surgery was associated with sociodemographic factors.

KIFC1 promotes aerobic glycolysis in endometrial cancer cells by regulating the c-myc pathway.

Endometrial cancer (EC) is a common gynecological malignant tumor worldwide. It is imperative to study pathogenesis and therapeutic targets for improving the prognosis of EC. The present study aimed to explore the function and mechanism of kinesin family member C1 (KIFC1) in EC. EC tumor and adjacent normal tissues were collected from 68 pairs of patients. The expression of KIFC1 in tissues and EC cells was analyzed by immunohistochemistry, qRT-PCR or western blot. MTT assay was used to test the cell viability. Flow cytometry was used to determine apoptosis and the cell cycle. Glucose uptake, lactate production, ATP contents and lactate dehydrogenase (LDH) activity were evaluated by a glucose metabolism kit. The expression of HMGA1, c-myc and glycolytic genes was assessed using western blot or qRT-PCR. A mouse xenograft model was established in BALB/c mice to detect tumor growth in vivo. KIFC1 was significantly upregulated in EC tumor tissues compared to adjacent normal control tissues. The upregulated expression of KIFC1 was correlated with poor prognosis in patients. Lentiviral-mediated overexpression of KIFC1 observably enhanced cell viability and reduced the apoptotic rate of Ishikawa and HEC-1B cells. Cell cycle progression was also expedited in the KIFC1 vector group. Moreover, overexpression of KIFC1 elevated glucose uptake, lactate production, ATP contents and LDH activity. However, knockdown of KIFC1 by short hairpin RNA (shRNA) showed the reverse effect on cellular functions. In addition, the expression of c-myc, GLUT1, LDHA and HK2 was increased by the KIFC1 vector. Moreover, HMGA1 regulated the expression of c-myc and glycolytic genes. Upregulated HMGA1 could rescue the effect of KIFC1 knockdown on cellular functions and the expression of glycolytic genes. Finally, KIFC1 knockdown inhibits tumor growth in vivo. The upregulation of KIFC1 was correlated with poor prognosis in EC. KIFC1 promoted aerobic glycolysis in endometrial cancer cells by regulating the HMGA1/c-myc pathway. KIFC1 may be a potential target for the diagnosis and therapy of EC.

N6-Methyladenosine-Related Long Noncoding RNAs as Potential Prognosis Biomarkers for Endometrial Cancer.

PurposeEndometrial cancer (EC) is a common gynaecologic malignancy with an increasing incidence rate and mortality in recent years. N6-methylandenosine (m6A)-related long noncoding RNA (lncRNA) plays a vital role in EC, emerging as one of the most abundant RNA modifications.Materials and MethodsThe Cancer Genome Atlas (TCGA) database and UCSC Xena were used to download data related to EC. Survival and univariate and multifactorial prognostic analyses were performed for m6A-related lncRNAs. The expression levels of the three lncRNAs were verified using q-PCR. A nomogram was used to create a clinical tool to assess overall survival. To investigate the relationship between m6A-related lncRNA and EC, we downloaded differential genes related to EC from the TCGA database and mined three m6A-related lncRNAs, namely SCARNA9, TRAF3IP2-AS1, and AL133243.2. The data were categorized into high- and low-risk groups based on m6A-associated lncRNA.ResultsSurvival analysis revealed that the high-risk group had a lower survival rate. Survival analysis of three m6A-associated lncRNAs revealed that cases with high expression of SCARNA9 tended to have a poorer prognosis, whereas the opposite was true for TRAF3IP2-AS1, AL133243.2. Univariate and multifactorial prognostic analyses suggested statistical differences in patients’ age, FIGO stage, pathological grade, risk score, and prognosis of EC, which was confirmed by results of the separate prognostic factor analysis for the three lncRNAs. Risk status was validated as an independent prognostic indicator, and the prognostic nomogram combined patient age, pathological stage, and FIGO classification to assess 3–5-year survival. Cases from high- and low-risk groups were analysed for the tumour microenvironment and immune cell scores, and stromal cell scores were found to be lower in the high-risk group. Correlations were analysed using different databases for immune cell classification.Conclusionm6A-related lncRNAs may play a key role in the diagnosis and treatment of EC as targets of prognosis and the immune microenvironment.

A Cholesterol Homeostasis-Related Gene Signature Predicts Prognosis of Endometrial Cancer and Correlates With Immune Infiltration.

Background: Endometrial cancer (EC) is one of the most common gynecological malignancies in women. Cholesterol metabolism has been confirmed to be closely related to tumor proliferation, invasion and metastasis. However, the correlation between cholesterol homeostasis-related genes and prognosis of EC remains unclear. Methods: EC patients from the Cancer Genome Atlas (TCGA) database were randomly divided into training cohort and test cohort. Transcriptome analysis, univariate survival analysis and LASSO Cox regression analysis were adopted to construct a cholesterol homeostasis-related gene signature from the training cohort. Subsequently, Kaplan-Meier (KM) plot, receiver operating characteristic (ROC) curve and principal component analysis (PCA) were utilized to verify the predictive performance of the gene signature in two cohorts. Additionally, enrichment analysis and immune infiltration analysis were performed on differentially expressed genes (DEGs) between two risk groups. Results: Seven cholesterol homeostasis-related genes were selected to establish a gene signature. KM plot, ROC curve and PCA in two cohorts demonstrated that the gene signature was an efficient independent prognostic indicator. The enrichment analysis and immune infiltration analysis indicated that the high-risk group generally had lower immune infiltrating cells and immune function. Conclusion: We constructed and validated a cholesterol homeostasis-related gene signature to predict the prognosis of EC, which correlated to immune infiltration and expected to help the diagnosis and precision treatment of EC.

Does Clinical and Biochemical Thyroid Dysfunction Impact on Endometrial Cancer Survival Outcomes? A Prospective Database Study.

Simple SummaryEndometrial cancer is the most common gynaecological cancer in high-income countries. Most women are diagnosed early and have an excellent prognosis, but those with advanced or recurrent disease have poor outcomes. The aim of this study was to determine whether clinical or biochemical thyroid dysfunction may contribute to survival outcomes following diagnosis and treatment for endometrial cancer. We analysed clinical data and serum thyroid hormone status of 333 women treated for endometrial cancer at a specialist cancer centre and followed up for a median of 35 months. Women with a diagnosis of hypothyroidism had improved overall, cancer-specific, and recurrence-free survival compared to those without. This may have important implications for our understanding of the mechanisms underpinning biologically aggressive disease and offer opportunities for therapeutic intervention.Endometrial cancer is the commonest gynaecological malignancy in developed countries, and women presenting with high risk or advanced disease have poor outcomes. Thyroid hormones play a key role in cellular metabolism and can influence cancer growth and invasion. Our aim was to evaluate the association between clinical and biochemical thyroid dysfunction and endometrial cancer survival outcomes. This was a prospective cohort study of women treated for endometrial cancer at a specialist centre. Clinical diagnosis of hypothyroidism was based on clinical and biochemical assessment, verified by general practitioner (GP) records. Pre-treatment serum samples were tested for thyrotropin (TSH), thyroid hormones (free T4 and total T3), and thyroid peroxidase antibodies. Kaplan–Meier survival estimates and log-rank tests were used to compare survival between groups, while Cox regression was used for multivariable analysis, adjusting for known confounders and effect modifications. In total, 333 women with median age and body mass index (BMI) of 66 years (interquartile range (IQR) 56, 73) and 33 kg/m2 (IQR 27, 41) respectively were included. A total of 51 (15.3%) women had a diagnosis of hypothyroidism, 39 (11.9%) had biochemical evidence of overt or subclinical hypothyroidism. Median follow-up was 35 months (IQR 21, 45) with 38 (11.7%) relapses and 50 (15.0%) deaths. Women with a diagnosis of hypothyroidism had improved overall survival (adjusted HR = 0.22, 95%CI 0.06–0.74, p = 0.02), cancer-specific survival (adjusted HR = 0.21, 95%CI 0.05–0.98, p = 0.04) and fewer recurrences (adjusted HR = 0.17, 95%CI 0.04–0.77, p = 0.02) than those who did not. Confirmatory studies should explore underlying mechanisms and the potential for therapeutic exploitation.

The cost of diagnosing endometrial cancer: Quantifying the healthcare cost of an abnormal uterine bleeding workup

ObjectiveThe evaluation of women with perimenopausal abnormal uterine bleeding (AUB) and postmenopausal bleeding (PMB) to detect endometrial cancer (EC) and its precursors is not standardized and can vary widely. Consequently, costs associated with the workup and management undoubtedly vary. This study aimed to quantify costs of AUB/PMB evaluation to understand the healthcare burden associated with securing a pathologic diagnosis. MethodsWomen ≥45 years of age presenting to a single institution gynecology clinic with AUB/PMB for diagnostic workup were prospectively enrolled February 2013–October 2017 for a lower genital tract biospecimen research study. Clinical workup of AUB/PMB was determined by individual provider discretion. Costs of care were collected from administrative billing systems from enrollment to 90 days post enrollment. Costs were standardized and inflation-adjusted to 2017 US Dollars (USD). ResultsIn total, there were 1017 women enrolled with 5.6% diagnosed with atypical hyperplasia or endometrial cancer (EC). Within the full cohort, 90-day median cost for AUB/PMB workup and management was $2279 (IQR $512–4828). Among patients with a diagnostic biopsy, median 90-day costs ranged from $2203 (IQR $499–3604) for benign or disordered proliferative endometrium (DPE) diagnosis to $21,039 (IQR $19,084-24,536) for a diagnosis of EC. ConclusionsThe costs for diagnostic evaluation of perimenopausal AUB and PMB vary greatly according to ultimate tissue-based diagnosis. Even reassuring benign findings that do not require further intervention—the most common in this study's cohort—yield substantial costs. The development of sensitive, specific, and more cost-effective diagnostic strategies is warranted.

Visceral Adipose Volume as a Predictor for Acute Bowel Toxicity in Patients Receiving Adjuvant Intensity-Modulated Radiation Therapy for Cervical or Endometrial Cancer

Relative to 3D conformal radiation therapy (RT), intensity modulated radiation therapy (IMRT) is associated with decreased acute bowel toxicity during adjuvant RT for gynecologic cancers. Delineating the peritoneal space as a 'bowel bag' is a common method to assess RT dose and volume parameters during treatment planning. However, there is a relative lack of evidence-based bowel bag dose/volume constraints that can be used to guide clinicians. Previously, we described a method to normalize dose/volume measures based on the proportion of adipose tissue within the bowel bag contour and demonstrated this technique more closely correlates with acute toxicity than standard measures. This work was criticized for including a heterogenous patient population of gastrointestinal and gynecologic cancer patients treated with definitive and adjuvant RT. Here, we report an updated analysis, limiting our patient population to those receiving adjuvant IMRT for gynecologic cancers.Eighteen consecutive patients treated with adjuvant pelvic +/- para-aortic IMRT following hysterectomy for a diagnosis of endometrial or cervical cancer at a single academic medical center were included. As previously described by Ganju et al, simulation CT scans were retrieved and the bowel bag was contoured per RTOG guidelines. Dosimetric data for V45 Gy (cc) and V40 Gy (%) was collected. Adipose tissue was auto-contoured using Hounsfield Unit thresholds. Visceral adipose ratio was defined as the volume of non-adipose tissue within the bowel bag divided by the total volume. This was multiplied by the above dosimetric variables to correct for uninvolved adipose tissue. Bowel function was assessed weekly during therapy using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. Baseline bowel scores were defined as those obtained at CT simulation or week 1 of therapy, and final scores were those occurring during week 4 of 5 of treatment. One-tailed spearman correlation coefficients were used to identify significant associations between acute bowel toxicity and bowel bag dose/volume measures.Eighteen patients met criteria for inclusion. Fifteen patients were treated for endometrial and three for cervical cancer. The median dose of radiation was 45 Gy. V40 Gy (%) and V45 Gy (cc) measures were not correlated with decline in EPIC bowel function, bother, or composite measures. However, adipose corrected V45 Gy(cc) showed significant correlation with bowel function decline (P = 0.04) and overall decline in bowel composite measure (P = 0.03).Adipose corrected bowel bag dose/volume measures (V45 Gy cc) may be used to predict acute bowel toxicity in patients receiving post-operative IMRT following a hysterectomy in endometrial and cervical cancers. Future studies will require validation in a larger patient population.D. Nganga: None. A. Hoover: None.

The Risk of Endometrial Hyperplasia and Malignancy May be Increased in Patients with Endometriosis

<h3>Study Objective</h3> The objective of our study is to further investigate the role of endometriosis on subsequent diagnosis of endometrial hyperplasia and malignancy (EHM). <h3>Design</h3> Retrospective cohort study <h3>Setting</h3> Single academic institution <h3>Patients or Participants</h3> All cases of histologically diagnosed endometriosis were evaluated between 2005 and 2020. Women over 18 years of age were included. All endometrial malignancies were included for analysis. Patients with a history of hysterectomy were excluded. <h3>Interventions</h3> No interventions were performed <h3>Measurements and Main Results</h3> Demographic information and past medical and surgical history were assessed. For the EHM cohort, oncologic data, endometriosis stage, patient age and body mass index (BMI) at time of diagnosis were collected. A total of 2,122 women with endometriosis were included. Of these, 198 (9.3%) were found to have co-existing eutopic endometrial hyperplasia (n=56) or malignancy (n=142). At the time of oncologic diagnosis, the mean age was 55.6 years and mean BMI was 33.1. Within the EHM group, 82.3% of endometriosis diagnoses were made at the time of their surgical management and the majority were stage 1 by ASRM criteria (70.0%). When comparing characteristics between those with and without a diagnosis of EHM, there was no significant difference in race, ethnicity, tobacco use, prior diagnosis of PCOS or diagnosis of breast or colon cancer. Significant differences were seen in type 2 diabetes (p<0.0001), hypertension (p<0.0001), prior use of tamoxifen (p=0.0021), gravidity (p=0.0331) and parity (p<0.0001). Statistical analysis was performed using chi-square and Mann-Whitney tests. A p-value of <0.05 was considered significant. <h3>Conclusion</h3> Compared to the population prevalence of less than 1% of both endometrial hyperplasia and malignancy, our study suggests that endometriosis may be a predictor of subsequent diagnosis of endometrial cancer and malignancy. Further research is needed to control for known confounders of endometrial hyperplasia and malignancy.

Use of antidepressants and endometrial-cancer risk: a nationwide nested case-control study.

Preclinical studies have suggested that antidepressant drugs may possess antineoplastic properties. In a nationwide case-control study, we examined the association between use of antidepressants and endometrial-cancer risk with a particular focus on selective serotonin reuptake inhibitors (SSRIs). From the Danish Cancer Registry, we identified all women with a histologically verified diagnosis of endometrial cancer between 2000 and 2016, and, for each woman, 15 age-matched controls. We obtained information on use of SSRIs, tricyclic antidepressants (TCAs) and other antidepressants based on records of filled prescriptions from the National Prescription Register. Using conditional logistic regression, we calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between use of antidepressants and endometrial-cancer risk compared with non-use. In active comparator analyses, SSRI use was compared with TCA use. The study population comprised 8164 cases and 122 432 controls. Compared with non-use, SSRI use was associated with an OR of 0.88 (95% CI 0.82-0.96) for endometrial cancer, whereas the association with TCA use was close to unity (OR 1.05, 95% CI 0.90-1.22). Use of other antidepressants yielded an OR of 0.86 (95% CI 0.71-1.03). We observed no apparent trends in associations according to cumulative amount. The inverse association with SSRI use persisted when compared with TCA use (OR 0.81, 95% CI 0.66-0.99). Use of SSRIs was associated with a decreased risk of endometrial cancer, whereas no inverse association appeared with use of TCAs. The antineoplastic potential of SSRIs should be investigated in future studies.