Diagnosis Of Endometrial Cancer Research Articles

Machine Learning for Endometrial Cancer Prediction and Prognostication.

Endometrial cancer (EC) is a prevalent uterine cancer that remains a major contributor to cancer-associated morbidity and mortality. EC diagnosed at advanced stages shows a poor therapeutic response. The clinically utilized EC diagnostic approaches are costly, time-consuming, and are not readily available to all patients. The rapid growth in computational biology has enticed substantial research attention from both data scientists and oncologists, leading to the development of rapid and cost-effective computer-aided cancer surveillance systems. Machine learning (ML), a subcategory of artificial intelligence, provides opportunities for drug discovery, early cancer diagnosis, effective treatment, and choice of treatment modalities. The application of ML approaches in EC diagnosis, therapies, and prognosis may be particularly relevant. Considering the significance of customized treatment and the growing trend of using ML approaches in cancer prediction and monitoring, a critical survey of ML utility in EC may provide impetus research in EC and assist oncologists, molecular biologists, biomedical engineers, and bioinformaticians to further collaborative research in EC. In this review, an overview of EC along with risk factors and diagnostic methods is discussed, followed by a comprehensive analysis of the potential ML modalities for prevention, screening, detection, and prognosis of EC patients.

To Identify Adenomatous Polyposis Coli Gene Mutation as a Predictive Marker of Endometrial Cancer Immunotherapy

The adenomatous polyposis coli (APC) gene is the chromatin-remodeling-related gene and a typical tumor suppressor. Patients with a high expression of programmed death-ligand 1 (PD-L1) or a high level of tumor mutational burden (TMB) may benefit from immunotherapy in endometrial cancer (EC). This study aimed to demonstrate the role of APC in the diagnosis and immunotherapy treatment of EC. We performed an integrative analysis of a commercial panel including 520 cancer-related genes on 99 tumors from an endometrial cancer cohort in China and DNA-seq data from The Cancer Genome Atlas (TCGA) to identify new gene mutations as endometrial cancer immunotherapy markers. We found that the significant mutant genes that correlated with the PD-L1 expression and TMB were related to the chromatin state and generated a discovery set having 12 mutated genes, including the APC gene, which was identified as a new marker for immunotherapy. Further analysis revealed that tumors with the APC mutation had high TMB, increased expression of PD-L1, and increased lymphocytic infiltration. Next, we verified that APC has an inactive mutation in EC, which may affect the immune response, including PD-L1 expression, microsatellite instability, and lymphocytic infiltrate. Furthermore, patients with the APC mutation had longer overall survival. Our study demonstrates that APC could play an important role in enhancing the response to endometrial cancer treatment, particularly immunotherapy.

Implementing universal upfront multi-gene panel testing in endometrial cancer: From cost to practical considerations

ObjectivesThe routine use of upfront universal germline genetic testing among patients with newly diagnosed endometrial cancer (EC) has been proposed to improve diagnosis of Lynch syndrome (LS) and discover pathogenic variants (PVs) in other cancer susceptibility genes. We propose an algorithm prioritizing upfront multi-gene panel testing (MGPT) for newly diagnosed EC patients. MethodsA decision analysis compared the cost of the current algorithm of universal mismatch repair (MMR) immunohistochemistry (IHC) for all EC cases to a new MGPT algorithm that employs upfront MGPT for all EC cases and reserves MMR IHC for the recurrent setting. The increase in the number of LS diagnoses using upfront MGPT, and the number of patients with PVs in BRCA1 and BRCA2 are also estimated. ResultsThe MGPT algorithm demonstrated a cost savings of $259 per patient. Assuming 66,950 new cases of EC per year, this would represent $17.1 M of cost savings per year. When applied to all new diagnoses of EC in one year, the MGPT algorithm identified 660 (1%) additional cases of LS that would have been missed with the current algorithm. An additional 660 (1%) EC patients with BRCA1 or BRCA2 PVs would be diagnosed only through implementation of universal MGPT. ConclusionsThe use of universal upfront MGPT is a practical consideration for patients with newly diagnosed EC for cost savings and improved diagnosis of highly penetrant cancer syndromes. Incorporation of germline genetic testing in the upfront setting represents an opportunity to improve access to genetic counseling and testing, and ultimately an avenue to achieve equity and improve the lives of our patients with EC and their families.

The opportunities and challenges of gynecologic cancer in precision medicine

In recent years, the diagnosis and treatment of gynecologic cancer have entered a new era with the development of precision medicine. The diagnosis and treatment modes for ovarian cancer, cervical cancer, and endometrial cancer are constantly adjusted. The application of molecular targeted drugs and the progress of surgical concepts and technology have greatly improved the survival of patients with ovarian cancer. Immunotherapy and targeted therapy have become a new hot spot in the treatment of cervical cancer. More clinical research data have been accumulated on the comparison of laparoscopic and open radical hysterectomy in cervical cancer. The surgical management of endometrial cancer has been improved, and molecular diagnostics are increasingly used to guide the diagnosis and treatment of endometrial cancer. Meanwhile, it's necessary to realize the limitations and challenges of precision medicine in gynecologic cancer.

Nodal Assessment in Endometrial Atypical Hyperplasia

Objective: Atypical endometrial hyperplasia (AH) is the neoplastic precursor more often associated with endometrial cancer (EC). Nowadays, 25–50% of patients subjected to hysterectomy for preoperative AH are diagnosed with EC at the final pathological analysis. Furthermore, there is no consensus on which preoperative AH patients would benefit from sentinel lymph node mapping. This study aimed to evaluate nodal assessment and preoperative cancer risk factors in preoperative AH patients undergoing nodal surgical staging. Methods: Patients undergoing surgical treatment for AH were retrospectively included in the analysis. Patients were divided into two groups (AH and EC groups) based on the final surgical pathology. The ESGO/ESTRO/ESP risk classification was used for EC cases. Design: This was a retrospective study. Results: Of the 207 AH patients treated, 152 cases met the inclusion criteria. Among preoperative AH patients with final EC diagnosis, 39 patients were in the low-risk group (25.7%), 8 in the intermediate-risk group (5.3%), 4 in high-intermediate (2.6%), and 3 patients were allocated in the high-risk group (2.0%). Fifty-four total patients underwent nodal surgical staging. Only one nodal micrometastasis (0.7%) was found at ultrastaging. Multivariate analysis showed abnormal uterine bleeding (AUB) (p = 0.01), hypertension (p < 0.01), and endometrial thickness ≥20 mm (p = 0.02) statistically more represented in patients with EC at final surgical analysis. EC risk was 2.9 (95% CI: 1.29–6.48) in AUB, 2.7 (95% CI: 1.06–6.92) in hypertension, and 3.1 (95% CI: 1.19–7.97) in endometrial thickness ≥20 mm cases. Limitations: The present study has limitations inherent in its retrospective nature. Conclusion: The overall risk of nodal metastases in preoperative AH patients was low. Conversely, 9.9% of the preoperative AH patients belonged to the intermediate or high-risk group for EC at the final histological examination. Preoperative cancer risk factors would identify AH patients for whom nodal staging could be suggested.

Tissue-Based Proteomic Profiling in Patients with Hyperplasia and Endometrial Cancer.

Uterine cancers are among the most prevalent gynecological malignancies, and endometrial cancer (EC) is the most common in this group. This study used tissue-based proteomic profiling analysis in patients with endometrial cancer and hyperplasia, and control patients. Conventional 2D gel electrophoresis, followed by a mass spectrometry approach with bioinformatics, including a network pathway analysis pipeline, was used to identify differentially expressed proteins and associated metabolic pathways between the study groups. Thirty-six patients (twelve with endometrial cancer, twelve with hyperplasia, and twelve controls) were enrolled in this study. The mean age of the participants was 46–75 years. Eighty-seven proteins were significantly differentially expressed between the study groups, of which fifty-three were significantly differentially regulated (twenty-eight upregulated and twenty-five downregulated) in the tissue samples of EC patients compared to the control (Ctrl). Furthermore, 26 proteins were significantly dysregulated (8 upregulated and 18 downregulated) in tissue samples of hyperplasia (HY) patients compared to Ctrl. Thirty-two proteins (nineteen upregulated and thirteen downregulated) including desmin, peptidyl prolyl cis-trans isomerase A, and zinc finger protein 844 were downregulated in the EC group compared to the HY group. Additionally, fructose bisphosphate aldolase A, alpha enolase, and keratin type 1 cytoskeletal 10 were upregulated in the EC group compared to those in the HY group. The proteins identified in this study were known to regulate cellular processes (36%), followed by biological regulation (16%). Ingenuity pathway analysis found that proteins that are differentially expressed between EC and HY are linked to AKT, ACTA2, and other signaling pathways. The panels of protein markers identified in this study could be used as potential biomarkers for distinguishing between EC and HY and early diagnosis and progression of EC from hyperplasia and normal patients.

Adverse Urinary System Outcomes among Older Women with Endometrial Cancer.

Endometrial cancer and its treatment may cause damage to the urinary system, but few large-scale studies have examined the incidence of urinary-related outcomes among endometrial cancer survivors. We investigated the risk of several urinary disease diagnoses among older women with endometrial cancer compared to women without a cancer history. Women ages 66 years and older with an endometrial cancer diagnosis during 2004-2017 (N=44,386) and women without a cancer history (N=221,219) matched 5:1 on age, race/ethnicity, and state were identified in the Surveillance, Epidemiology, and End Results-Medicare linked data. ICD-9 and -10 diagnosis codes were used to identify urinary outcomes in the Medicare claims data. Cumulative incidences (IP) of urinary outcomes were estimated among women with and without endometrial cancer. Multivariable Cox proportional hazards regression models were used to estimate hazards ratios (HR) for urinary outcomes comparing women with and without endometrial cancer. HRs were also used to identify characteristics associated with urinary outcomes among endometrial cancer survivors. Relative to women without cancer, endometrial cancer survivors had an increased risk of urinary system diagnoses, including renal failure (5-year IP: 25% vs 14%; HR=1.50; 95% CI: 1.47-1.53), chronic kidney disease (5-year IP: 20% vs 14%; HR=1.25; 95% CI: 1.22-1.28), calculus of the urinary tract (5-year IP: 7% vs 4%; HR=1.55; 95% CI: 1.50-1.61), lower urinary tract infection (5-year IP: 55% vs 33%; HR=1.75; 95% CI: 1.72, 1.78), and bladder diseases (5-year IP: 10% vs 6%; HR=1.57; 95% CI: 1.52, 1.62). These associations persisted in analyses limited to 1+ and 5+ years after endometrial cancer diagnosis. Non-Hispanic Black or Hispanic race/ethnicity, higher comorbidity index, higher stage or grade cancer, non-endometrioid histology, and treatment with chemotherapy and/or radiation were often predictors of urinary outcomes among women with endometrial cancer. Our results suggest that, among older women, the risk of urinary outcomes is elevated after endometrial cancer. Monitoring for urinary diseases may be a critical part of long-term survivorship care for older women with an endometrial cancer history.

Community-based outpatient cancer rehabilitation services for women with gynecologic cancer: acceptability and impact on patient-reported outcomes.

Women with gynecologic cancers often experience functional impairments impacting quality of life. Physical and occupational therapy (PT/OT) treat functional impairment; however, the acceptability and impact of these services for women with gynecologic cancer are unknown. We reviewed rehabilitation charts of women with gynecologic cancer who received PT/OT (i.e., patients) in 2019 and completed patient-reported outcome measures (PROMs) selected by their therapist at intake (pre) and discharge (post). We calculated descriptive statistics for patient, rehabilitation, and acceptability (0-10) data. For PROM data, we used paired samples t-tests to evaluate pre-post change, and then calculated effect size (Hedge's g) and the proportion who achieved a minimal detectable change (MDC). PT/OT patients (N = 84) were 64.63 ± 11.04years old with predominant diagnoses of ovarian (41.7%) or endometrial (32.1%) cancer. They attended a median of 13 sessions (IQR = 8.0-19.0). Sessions were predominantly PT (86%) vs. OT (14%). Median acceptability was 10 (IQR = 9.8-10.0). Pre-post improvement was observed for each of the 17 PROMs used by therapists. Significant improvement (p < .05) was observed for four PROMs: the Patient-Specific Functional Scale (M∆ = 2.93 ± 2.31, g = 1.47, 71% achieved MDC), the Lower Extremity Functional Scale (M∆ = 12.88 ± 12.31, g = 0.61, 60% achieved MDC), the Lymphedema Life Impact Scale (M∆ = 20.50 ± 20.61, g = 1.18, 58% achieved MDC), and the Modified Fatigue Impact Scale (M∆ = 6.55 ± 9.69, g = 0.33, 7% achieved MDC). PT/OT was acceptable and improved patient-reported outcomes for women with gynecologic cancers. Future research is needed to establish gynecologic-specific guidelines for referral and PT/OT practice.

APC mutations as a predictive marker of endometrial cancer immunotherapy: a retrospective cohort study

The APC regulator of WNT signalling pathway gene (previously known as adenomatous polyposis coli gene; APC), located on 5q22.2, is a chromatin remodelling-related gene and a typical tumour suppressor. Patients with high expression of PD-L1 or a high tumour mutational burden have been reported to benefit from immunotherapy in endometrial cancer. The objective of this study was to show that APC is a new biomarker target for the diagnosis and treatment of endometrial cancer by analysing the correlation of APC mutations with PD-L1 expression or tumour mutational burden. We did an integrative analysis of a commercially available panel (Burning Rock Biotech, Guangzhou, China) including 520 cancer-related genes on 99 tumour samples from an endometrial cancer cohort in China and DNA-seq data from The Cancer Genome Atlas to identify new gene mutations as endometrial cancer immunotherapy markers. To discover the effect of gene mutations on endometrial cancer, we assessed the correlation between gene mutations and tumour immune microenvironment, and explored the immune microenvironment in endometrial cancer, including tumour mutational burden, PD-L1 expression, and lymphocytic infiltration. We found that the relevant mutated genes were related to the chromatin state and generated a discovery set including 12 mutated genes that significantly correlated with PD-L1 expression and tumour mutational burden. We pinpointed the APC gene, which was mutated in 18 (18%) of 99 tumour samples, as a new potential biomarker for immunotherapy. Further analysis showed that tumours with an APC mutation had a high tumour mutational burden, increased expression of PD-L1, and increased lymphocytic infiltration. By assessing the relationship between immunotherapy biomarkers and APC, we verified that APC has inactive mutations (eg, missense mutations, truncating mutations, and a mixture of missense and truncating mutations) in endometrial cancer, which might affect the immune response, including PD-L1 expression, microsatellite instability, and lymphocytic infiltrate. From The Cancer Genome Atlas data, we also found that patients with the APC mutation had longer overall survival. Our study shows that APC could have an important role in enhancing the response to endometrial cancer treatment, particularly immunotherapy. The study was supported by the National Natural Science Foundation of China (grant numbers 81472427, 32070583, 81672574, and 81702547), the Shanghai Health System Outstanding Talents Program (grant number 2018YQ23), the Shanghai New Frontier Technology Project (grant number SHDC12015110), and the Shanghai Municipal Medical and Health Discipline Construction Projects (grant number 2017ZZ02015).

Endometrial biopsy under direct hysteroscopic visualisation versus blind endometrial sampling for the diagnosis of endometrial hyperplasia and cancer: Systematic review and meta-analysis.

Endometrial cancer is the most common gynaecological neoplasia in western countries. Diagnosis of endometrial cancer requires an endometrial biopsy. A good quality endometrial biopsy allows not only the identification of the pathology, but also preoperative histologic subtype classification. Endometrial biopsy can be performed under direct hysteroscopic visualisation, but also using blind sampling techniques. To compare endometrial biopsy performed under direct hysteroscopic visualisation versus blind sampling for the diagnosis of endometrial hyperplasia and cancer. Systematic review and meta-analysis. Electronic databases were searched from their inception until March 2022.We included all studies comparing endometrial biopsy performed under direct hysteroscopic visualisation versus blind endometrial sampling. Sample adequacy, failure rate to detect endometrial cancer or endometrial hyperplasia, and rate of detection of endometrial cancer. The summary measures were reported as relative risk (RR) with 95% of confidence interval (CI). Four studies with a total of 1,295 patients were included. Endometrial biopsy under direct hysteroscopic visualisation was associated with a significantly higher rate of sample adequacy (RR 1.13, 95% CI 1.10 to 1.17), and significantly lower risk of failure to detect endometrial cancer or endometrial hyperplasia (RR 0.16, 95% CI 0.03 to 0.92) compared to blind endometrial sampling. However, there was no significant difference between endometrial biopsies taken under direct hysteroscopic visualisation or blindly, with or without a preceding diagnostic hysteroscopy, in the rate of detection of endometrial cancer (RR 0.18, 95% CI 0.03 to 1.06). Hysteroscopic endometrial biopsy under direct visualisation is associated with significantly higher rate of sample adequacy and is comparable to blind endometrial sampling for the diagnosis of endometrial cancer and precancer. Hysteroscopic endometrial biopsy under direct visualisation would be expected to reduce diagnostic failure for endometrial cancer compared to blind endometrial sampling.

P-696 Serum androgen levels and risk of endometrial hyperplasia and malignancy in patients with polycystic ovarian syndrome: a cross-sectional analysis

Abstract Study question In patients with polycystic ovarian syndrome (PCOS), are serum androgen levels (total and free testosterone) associated with the risk of endometrial hyperplasia or cancer? Summary answer Patients with PCOS diagnosed with endometrial hyperplasia or cancer had statistically significantly lower serum levels of androgens compared to PCOS patients with a normal endometrium. What is known already PCOS affects as many as 12% of women of reproductive age. Women with PCOS are almost three times as likely to develop endometrial cancer as women without PCOS, and endometrial hyperplasia precedes cancer in 36% of cases. Known risk factors of endometrial hyperplasia include anovulation, obesity, and resultant unopposed estrogen stimulation of the endometrium. A hallmark of PCOS is hyperandrogenism, however the effect of androgens on the endometrium is unclear. Study design, size, duration This was a cross-sectional, retrospective study of patients aged 18-40, being evaluated for oligomenorrhea and/or PCOS in the Reproductive Endocrinology Clinic at Los Angeles County Hospital, California, USA. All patients underwent an endometrial biopsy and serum measurement of free and total testosterone, estradiol, and hemoglobin A1c. Patients diagnosed with PCOS and with an endometrial biopsy diagnosis were included in the study. Patients on any hormonal therapy were excluded. Participants/materials, setting, methods In all patients included in the study, serum androgen levels (free and total testosterone) were measured by mass spectrometry. All endometrial biopsies were analyzed by an experienced histopathology, and all diagnoses of endometrial hyperplasia or cancer were confirmed by histologic studies. Main results and the role of chance Using the Rotterdam criteria, a total of 232 patients were diagnosed with PCOS during the study period. Of these patients, 161 patients (70%) had a normal endometrium, 19 (8%) were diagnosed with endometrial hyperplasia (EH) without atypia, 38 (16%) were diagnosed with EH with atypia, and 14 (6%) were diagnosed with endometrial cancer. Patients with a normal endometrium had a mean total testosterone of 60.9 ng/dL and mean free testosterone of 9.3 ng/dL. Relatively, patients with EH without atypia, EH with atypia, and endometrial cancer had lower mean total testosterone levels of 50.1 ng/dL, 45.5 ng/dL, and 30.1 ng/dL, respectively (p-values 0.04, 0.02, 0.001, respectively), as well as lower mean free testosterone levels of 8.2 pg/mL, 6.7 pg/mL, and 5.5 pg/mL, respectively (p-values 0.04, 0.03, and 0.01, respectively). There was no significant difference in age, parity, BMI, estradiol levels, or hemoglobin A1c between the four groups. Limitations, reasons for caution Limitations of our study include its retrospective nature. Furthermore, hormone levels were only measured in the serum, and not in the endometrial tissue directly, which would give the most insight into their actions on the endometrium. Wider implications of the findings Our findings suggest that androgens have a protective effect on the endometrium against endometrial hyperplasia and cancer. Further studies are needed to evaluate the therapeutic potential role of androgens in the prevention or treatment of these conditions. Trial registration number not applicable

PLK3 amplification and tumor immune microenvironment of metastatic tumors are linked to adjuvant treatment outcomes in uterine serous cancer.

Uterine serous carcinoma (USC), an aggressive variant of endometrial cancer representing approximately 10% of endometrial cancer diagnoses, accounts for ∼39% of endometrial cancer-related deaths. We examined the role of genomic alterations in advanced-stage USC associated with outcome using paired primary-metastatic tumors (n = 29) treated with adjuvant platinum and taxane chemotherapy. Comparative genomic analysis of paired primary-metastatic patient tumors included whole exome sequencing and targeted gene expression. Both PLK3 amplification and the tumor immune microenvironment (TIME) in metastatic tumors were linked to time-to-recurrence (TTR) risk without any such association observed with primary tumors. TP53 loss was significantly more frequent in metastatic tumors of platinum-resistant versus platinum-sensitive patients and was also associated with increased recurrence and mortality risk. Increased levels of chr1 breakpoints in USC metastatic versus primary tumors co-occur with PLK3 amplification. PLK3 and the TIME are potential targets for improving outcomes in USC adjuvant therapy.

Circulating microRNAs as Potential Biomarkers for the Diagnosis of Endometrial Cancer: a Meta-Analysis.

Endometrial cancer (EC) is the most common female genital tract malignancy worldwide. Many investigators have confirmed the possibility of using circulating miRNAs to diagnose EC; however, the results were inconsistent. Therefore, we performed the current meta-analysis to systematically evaluate the diagnostic value of circulating miRNAs in EC. We carefully searched relevant articles published prior to February 15, 2022 in the databases of PubMed, Embase, Web of Science, Cochrane Library, Wanfang database, and China National Knowledge Infrastructure (CNKI) based on PRISMA statement. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to test the diagnostic accuracy. Furthermore, subgroup analyses were performed to identify the potential sources of heterogeneity, and the Deeks' funnel plot asymmetry test was used to evaluate the potential publication bias. Twenty-one studies from 12 articles including a total of 2305 participants (1341 EC patients and 964 controls) were included in the current diagnostic meta-analysis. The overall pooled results of miRNA for EC diagnosis were: sensitivity, 0.84 (95% CI: 0.79-0.88); specificity, 0.87 (95% CI: 0.79-0.91); PLR, 6.3 (95% CI: 3.9-10.0); NLR, 0.18 (95% CI: 0.13-0.25); DOR, 35 (95% CI: 17-71); and AUC was 0.91 (95% CI: 0.89-0.94). Subgroup analysis suggested that miRNA cluster, serum type, and large sample sizes showed a better diagnostic accuracy. Moreover, there was no significant publication bias. Circulating miRNAs have great potential as novel non-invasive biomarkers for EC diagnosis.

Gynecological Cancers in Lynch Syndrome: A Comparison of the Histological Features with Sporadic Cases of the General Population.

Introduction: About 5% of endometrial cancers (ECs) are attributed to an inherited predisposition, for which Lynch syndrome (LS) accounts for the majority of cases. Women with LS have a 40–60% predicted lifetime risk of developing EC, in addition to a 40–80% lifetime risk of developing colorectal cancer and other cancers. In this population, the lifetime risk of developing ovarian cancer (OC) is 10–12%. Object: to compare the histopathological features of LS-associated EC and OC with sporadic cancers in order to evaluate whether there are differences in terms of age at diagnosis, site of occurrence in the uterus, histological type, stage at diagnosis, and tumor grading. Materials and methods: we compared data obtained from 96 patients with LS-associated gynecological cancers (82 with EC and 14 with OC) to a control group (CG) of 209 patients who developed sporadic EC, and a CG of 187 patients with sporadic OC. Results: The mean age at diagnosis of LS-associated EC and OC was much lower than in the control groups. In both groups with EC, the endometrioid histotype was the most frequently occurring histotype. However, among LS women there was a significantly higher incidence of clear cell tumors (11% versus 2.4% in the CG, p = 0.0001). Similar to the sporadic cancer cases, most of the LS-associated ECs presented at an early stage (89% of cases at FIGO I-II stage). In the LS group, the tumor frequently involved only the inner half of the endometrium (77% of cases, p < 0.01). In the LS group, 7.3% of ECs were localized to the lower uterine segment (LUS), whereas no cancer developed in the LUS in the CG. No serous OCs were diagnosed in the LS group (versus 45.5% in the CG, p = 0.0009). Most of the LS-associated OCs presented at an early stage (85% of cases at FIGO I-II stages, p < 0.01). Conclusion: LS-associated EC and OC seem to have peculiar features, occurring at a younger age and at an earlier stage. In LS, EC less frequently involves the outer half of the endometrium, with a more frequent occurrence in the LUS. The presence of clear cell EC was more frequently observed, whereas in OC, the predominant histotype was endometrioid.

ERRγ, a Novel Biomarker, Associates with Pathoglycemia of Endometrial Cancer to Predict Myometrial Invasion.

We aim to investigate the correlation between the expression of estrogen-related receptor γ (ERRγ) and endometrial cancer (EC) progression and to evaluate the potential of ERRγ as a new biomarker for EC diagnosis. We analyzed the ERRγ expression profile and the correlation with the corresponding clinical characteristics of EC samples from The Cancer Genome Atlas (TCGA), the Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, and the International Cancer Genome Consortium (ICGC) databases. Immunohistochemical (IHC) analysis was conducted on tissue samples, and enzyme linked immunosorbent assay (ELISA) was used in serum samples to detect the levels of ERRγ. The diagnostic performance of ERRγ proteins was assessed using the receiver operating characteristic (ROC). ERRγ showed notably higher expression in EC tissues than in normal endometrium tissues (P < 0.001), which was consistent with the result of TCGA. Overexpression of ERRγ was significantly associated with deep myometrial invasion of EC (P=0.004), and fasting blood glucose (FBG) was higher in EC patients with deep myometrial invasion than in those with superficial myometrial invasion (P=0.040). Further analysis using ELISA showed that the serum ERRγ level was positively correlated with FBG (R = 0.355, P < 0.001). ERRγ is overexpressed in EC and may be involved in regulating glucose metabolism and promoting myometrial invasion of EC. In addition, the area under the ROC curve (AUC) for ERRγ was 0.834, in distinguishing EC patients from healthy individuals, presented 84.0% and 80.0% sensitivity and specificity, respectively, and serum ERRγ has a good diagnostic performance in distinguishing EC patients from healthy people and may be a promising noninvasive biomarker in EC.

Integrated Bioinformatic Analysis of DNA Methylation and Immune Infiltration in Endometrial Cancer.

Background Endometrial cancer greatly threatens the health of female. Emerging evidences have demonstrated that DNA methylation and immune infiltration are involved in the occurrence and development of endometrial cancer. However, the mechanism and prognostic biomarkers of endometrial cancer are still unclear. In this study, we assess DNA methylation and immune infiltration via bioinformatic analysis. Methods The latest RNA-Seq, DNA methylation data, and clinical data related to endometrial cancer were downloaded from the UCSC Xena dataset. The methylation-driven genes were selected, and then the risk score was obtained using “MethylMix” and “corrplot” R packages. The connection between methylated genes and the expression of screened driven genes were explored using “survminer” and “beeswarm” packages, respectively. Finally, the role of VTCN1in immune infiltration was analyzed using “CIBERSORT” package. Results In this study, 179 upregulated genes, and 311 downregulated genes were identified and found to be related to extracellular matrix organization, cell–cell junctions, and cell adhesion molecular binding. The methylation-driven gene VTCN1 was selected, and patients classified to the hypomethylation and high expression group displayed poor prognosis. The VTCN1 gene exhibited highest correlation coefficient between methylation and expression. More importantly, the hypomethylation of promoter of VTCN1 led to its high expression, thereby induce tumor development by inhibiting CD8+ T cell infiltration. Conclusions Overall, our study was the first to reveal the mechanism of endometrial cancer by assessing DNA methylation and immune infiltration via integrated bioinformatic analysis. In addition, we found a pivotal prognostic biomarker for the disease. Our study provides potential targets for the diagnosis and prognosis of endometrial cancer in the future.

Image processing and machine learning approaches for the automatic diagnosis of endometrial cancer

In many medical imaging based diagnosis, Deep Learning (DL) algorithms play an essential role. A DL algorithm can be used to identify abnormal and normal cells in the uterus's endometrium in order to discover Endometrial Cancer (EC) cells. EC is difficult to diagnose since it develops without causing any symptoms. DL algorithm can distinguish between normal, abnormal, and malignant cells, producing more accurate findings than screening by hand procedures such as liquid cytology and Pap smear test. For the accurate and easier detection of EC cells, DL employs multiple architectures. The findings of an analysis and survey of the many forms of DL architecture, as well as their accuracy and performance, are addressed in this work. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are the most modalities of advanced imaging used for the non-invasive diagnosis of EC. EC is considered as the fourth most prevalent malignancy in women and one of the common most gynaecological cancers. Diagnostic imaging in clinical evaluation with has not been proven yet to be precise enough to substitute surgical staging in determining the spread of cancer. It may allow for improved surgical process optimization and a more customised therapeutic plan.

Serum miRNA-204-5p as a potential non-invasive biomarker for the diagnosis of endometrial cancer with sentinel lymph node mapping.

The lymph node status is one of the most critical prognostic factors used in determining adjuvant treatment in endometrial cancer (EC). Lymphadenectomy is associated significant surgical and postoperative risks. The use of sentinel lymph node mapping (SLNM) has emerged as an alternative method to complete lymphadenectomy in EC. However, there remains controversy surrounding the use of SLNM in high-risk disease and its false-negative rate (3%). The authors previously identified miR-204-5p as a tumor-suppressor miRNA associated with lymph node metastasis in EC tissues. The present study demonstrated that serum miR-204-5p in patients with EC has the potential for use as an early diagnostic biomarker combined with SLNM to assess the lymph node status prior to surgery. The present study also aimed to identify the optimal cut-off value of serum miR-204-5p. The relative expression levels of miR-204-5p were detected using reverse transcription-quantitative PCR in the serum of 52 patients with EC (total SLNM). A total of 20 patients diagnosed with ovarian cysts, 20 patients diagnosed with myoma, and 20 participants diagnosed with endometrial polyps or endometrial hyperplasia were included as the control group. miR-204-5p expression was also detected in lymph node tissues using in situ hybridization. The results revealed that serum miR-204-5p expression was downregulated in patients with EC compared with its expression in patients with benign ovarian cysts, myoma and endometrial hyperplasia/polyps (P<0.01). In accordance with the final pathological evaluation, patients with EC with a positive SLN status had a significantly lower level of miR-204-5p compared with those with a negative SLN status (P<0.01). The area under the ROC curve of miR-204-5p was 0.923, 95% CI (0.847-1.000), and the diagnostic value had a sensitivity of 87.2% and specificity of 80.0%, with an optimal cut-off value of 0.253. On the whole, it was demonstrated that a lower miR-204-5p expression is associated with lymph node metastasis in these SLN(+) EC tissues, indicating that the downregulation of serum miR-204-5p in patients with EC has potential for use as an early diagnostic biomarker combined with SLNM. In addition, with a cut-off value of 0.253, it appeared optimal for the prediction of lymph node metastasis in EC.

Role of Nucleolin in Endometrial Precancerous Hyperplasia and Carcinogenesis: Ex Vivo and In Silico Study.

Endometrial cancer (EC) is the most common gynaecological malignancy. Nucleolin (NCL) is involved in rDNA transcription, cell proliferation, and apoptosis, with high expression associated with worse overall survival (OS) in other adenocarcinomas. Our aims were to assess NCL gene and protein expression and explore the differential expression of NCL-associated genes (NAGs) in endometrial carcinogenesis. Endometrial samples were obtained from 157 women to include healthy, hyperplastic (EH), EC, and metastatic groups. RT-qPCR and immunohistochemistry were employed to assess NCL gene and protein levels. In silico analysis of NAGs in TCGA and GEO datasets was performed, with the prognostic value determined via Human Protein Atlas. NCL mRNA level of EC was lower than in healthy post-menopausal endometrium (p < 0.01). EH samples had lower NCL immuno-expression scores than healthy pre-menopausal (p < 0.001), benign post-menopausal (p < 0.01), and EC (p < 0.0001) samples. Metastatic lesions demonstrated higher NCL quick scores than primary tissue (p = 0.04). Higher NCL Immuno quick scores carried a worse OS in high-grade EC (p = 0.01). Interrogating Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) and Uterine Carcinosarcoma (TCGA-UCS) cohorts revealed NCL to be the most highly upregulated gene in carcinosarcoma, with S100A11, LMNB2, RERG, E2F1 and CCNA2 representing key dysregulated NAGs in EC. Since NCL is implicated in transforming hyperplastic glands into cancer, with further involvement in metastasis, it is suggested to be a promising target for better-informed diagnosis, risk stratification, and management of EC.

Hysterectomy as a risk-reducing procedure in BRCA1 and BRCA2 women.

10611 Background: BRCA1/2 pathogenic variants (PV) are associated with an increased lifetime risk of developing several malignancies, particularly breast (BC) and ovarian (OC) cancers. The association between BRCA1/2 and endometrial cancer (EC) is controversial. Therefore, adding hysterectomy (HT) to risk-reducing (RR) bilateral salpingo-oophorectomy (BSO) is of uncertain benefit. In our multidisciplinary group this decision is personalized and takes in account other gynaecological pathologies or, for BC survivors, tamoxifen treatment. Objectives of this study are to assess the risk of EC on BRCA1/2 families registered in our program and to discuss the role of prophylactic HT in BRCA1/2 carriers. Methods: Pathologic confirmed EC cases were extracted from the prospective follow up cohort of 949 women diagnosed with a BRCA1/ 2 PV through the hereditary breast, ovarian and prostate program at our centre. Data was collected from the medical records. Results: Of the 949 women, 345 (36.3%) were diagnosed with a BRCA1 PV, 603 (63.5%) with a BRCA2 PV and 1 (0.1%) with PV in both genes. Of all women, 648 (68.3%) had a previous cancer diagnosis while 291 (30.7%) were in primary risk management. Excluding non-melanoma skin cancer, EC was the fourth most frequent neoplasia: BC (553, 85.3%), ovarian, fallopian and peritoneal cancer (117, 18.1%), thyroid cancer (15, 2.3%) and EC (8, 1.2%). BSO with HT was performed in 372 (39.1%) women: RR in 259 (69.6%; BRCA1 36.7%, BRCA2 63.3%, history of cancer 75.7%, no history of cancer 24.3%) and therapeutic in 113 (30.4%; ovarian/fallopian cancer 92.0%, uterine cancer 8.0%). BSO alone was performed in 174 (18.3%), being RR in 170 (97.7%; BRCA1 34.7%, BRCA2 65.3%, history of cancer 72.9%, no history of cancer 27.1%). HT alone was performed in 3 (benign disease). Regarding family phenotype, we found another 2 cases of EC in possible BRCA carriers. For these 10 cases of EC, median age of diagnosis was 58.5 years (42-75), 7 in BRCA1 and 3 in BRCA2 patients (pts). Pathology: endometrioid (5), serous (1), mixed (2, 1 endometrioid and serous and 1 endometrioid, squamous cell and seromucous) and carcinosarcoma (2). Six (out of 10) pts had previous BC: 4 BRCA1 (2 triple negative, 2 luminal-like) and 2 BRCA2 (2 luminal-like), 4 of them had previous tamoxifen use (2 BRCA1, 2 BRCA2). In 1 case the diagnosis of EC occurred after RR BSO ( BRCA1, no tamoxifen use) and another during the RR surgery ( BRCA2, tamoxifen use). There was no significant association of EC with BRCA1 or BRCA2 (two-sided p= 0.149). EC was the cause of dead in 5 pts (50%), all BRCA1. Conclusions: EC was the fourth most frequently cancer registered in our cohort of BRCA1/2 women. BRCA1 women, representing around 1/3 of all cohort, had 70% of all EC diagnoses. This apparent excess of BRCA1 EC diagnoses was not statistically significant. Tamoxifen may be a confounding factor. While an association was not confirmed at this time, our data also reinforces the need to discuss HT with our BRCA1/2 pts.