Diagnosis Of Endometrial Cancer Research Articles

Direct next-generation sequencing analysis using endometrial liquid-based cytology specimens for rapid cancer genomic profiling.

Genomic examination of cytology specimens is often performed on cell blocks or conventional smears rather than on liquid-based cytology (LBC) specimens. Since LBC specimens preserve high-quality DNA, cancer genome profiling using next-generation sequencing (NGS) is also attainable from residual LBC specimens. One of the advantages of using LBC specimens for NGS is that it allows direct extraction of DNA from residual specimens, avoiding a sacrifice of smear slides and minimizing genomic profiling processing time. Endometrial LBC specimens were subjected to NGS analysis to validate the practicality of rapid cancer genomic profiling in a pathology laboratory. The extracted DNA was subjected to NGS using a customized cancer gene panel comprising 56 genes and 17 microsatellite regions. The workflow strategy was defined, and the processing time estimated for specimen sampling, cell counting, NGS run, and genome profiling. NGS analysis of most LBC specimens revealed somatic mutations, tumor mutation burden, and microsatellite instability, which were almost identical to those obtained from formalin-fixed paraffin-embedded tissues. The processing time for direct NGS analysis and cancer genomic profiling of the residual LBC specimens was approximately 5 days. The residual LBC specimens collected using endometrial cytology were verified to carry a high tumor fraction for NGS analysis and could serve as an alternate source for rapid molecular classification and diagnosis of endometrial cancers, as a routine process in a pathology laboratory.

The Correlation of the IETA Ultrasound Score with the Histopathology Results for Women with Abnormal Bleeding in Western Romania.

In the early differential diagnosis of endometrial cancer (EC), decisive and mandatory histological aspects are considered, in addition to obvious clinical manifestations. In addition, sonographic aspects are characteristic in relation to the stage, degree, and histological types of identified cancer. This bi-center retrospective observational study included 594 women with abnormal uterine bleeding outside pregnancy, for which a biopsy was performed in the Obstetrics and Gynecology Departments of the Emergency County Hospitals of Arad and Timis Counties, Romania, between 2015 and 2019. Most of the cases were represented by EC or endometrial hyperplasia (EH). Of the 594 cases, 25.5% (n = 153) were EC at women aged between 41 and 85 years. High International Endometrial Tumor Analysis (IETA) scores (3, 4) were associated with a relative risk of 2.9335 compared with other endometrial lesions (95% CI 2.3046 to 3.734, p < 0.0001, NNT 1.805). Histological aspects and pelvic ultrasound using IETA scores represent valuable noninvasive assets in diagnosing and differentiating endometrial cancer from benign uterine pathology.

HE4 in the Diagnostic Approach of Endometrial Cancer in Patients with Postmenopausal Bleeding, the METRODEC Protocol: Protocol for a Multicenter Prospective Study.

Background: Endometrial cancer is the most common pelvic gynecological cancer in France. The most frequent symptom is post-menopausal bleeding and is one of the primary reasons for consultation in gynecological emergencies. The treatment is very codified and consists of a surgical intervention for anatomopathological analysis. The latter is frequently reassuring. These interventions are often performed in mild situations and there is currently no element to be sufficiently reassuring to avoid surgery. This study aims to explore the sensitivity of an innovative marker: Human Epididymis 4 (HE4) in the diagnosis approach of endometrial cancer in case of postmenopausal bleedings. Methods: This is a prospective multicenter diagnostic study with three centers involved. Inclusion criteria are any patient with post-menopausal bleeding who is to undergo hysteroscopy, endometrial biopsy, or endometrial resection. In accordance with the recommendations for the management of post-menopausal bleedings, the medical conduct consists of performing a clinical examination, an ultrasound and, in general, even in case of paraclinical examination reassuring, an anatomopathological analysis. This pathological analysis can be obtained in several ways: biopsy, hysteroscopy-curettage (which is the most frequently performed surgery), and hysterectomy. Our protocol consists of taking a blood sample from each woman who will undergo one of the interventions mentioned above. The dosage of HE4 and CA125 requires the withdrawal of an additional heparinized tube during the preoperative assessment usually performed. This research is therefore classified as non-interventional. The primary outcome is to evaluate the sensitivity of the HE4 marker in patients with postmenopausal bleeding in the diagnosis of endometrial cancer. The secondary outcomes are other parameters (specificity, VPP, VPN) of HE4, Evaluating the diagnostic capabilities of the CA125 marker alone and associated with HE4, as well as those of the REM and REM-B algorithms. We aim to include 100 patients over a period of one year in three centers. Discussion: As of now, there is no biological marker used in routine practice in the diagnosis of endometrial cancer. The ultimate goal of HE4 in endometrial cancer is to avoid surgery for those who are identified as non-sick. This study is the precursor of others for use in routine practice, HE4 would represent a great help to diagnosis if our study demonstrates it as reliable in the management of these patients and avoid many unnecessary and risky surgeries.

A RARE CASE OF CLEAR CELL CARCINOMA OF ENDOMETRIUM IN A POST-MENOPAUSAL WOMAN- A HISTOPATHOLOGICAL CASE REPORT

Clear cell carcinoma of endometrium is a rare but aggressive malignancy with high predisposition of early extra-uterine spread. It commonly presents with vaginal bleeding or discharge. Less commonly, it may be diagnosed subsequent to an abnormal pap smear. Endometrial biopsy is ideally the first step for early diagnosis of such unfavourable endometrial cancer. Histopathological diagnosis is mandatory to confirm the presence of clear cells in the endometrial sample before planning the course of treatment. Here, we report a case of a postmenopausal woman who presented with vaginal bleeding without a specific medical history. Endometrial biopsy was done and sample was sent to our department of Pathology for histopathological diagnosis. We report the case from a histopathological perspective with a brief review of the relevant literature.

Estimated Performance of Transvaginal Ultrasonography for Evaluation of Postmenopausal Bleeding in a Simulated Cohort of Black and White Women in the US

Black women in the US with endometrial cancer (EC) are more likely to be diagnosed with advanced-stage disease independent of insured status and histologic type. The most common way of diagnosing EC at early stages is through screening of people with postmenopausal bleeding to detect endometrial thickness (ET). This approach may disproportionately underperform in Black women secondary to a higher prevalence of fibroids and nonendometrioid EC in this population, both of which affect the quality of ET measurement. To compare the performance of recommended transvaginal ultrasonography (TVUS) ET thresholds as a screening method to prompt endometrial biopsy by race in a simulated cohort of symptomatic women. In a simulated retrospective cohort study, based on data from Surveillance, Epidemiology, and End Results (SEER) national cancer registry 2012-2016; the US census; and published estimates of ET distribution and fibroid prevalence, diagnostic test characteristics of the 3-mm or more, 4-mm or more, and 5-mm or more ET thresholds for biopsy to capture EC diagnoses were calculated. The simulated cohort was constructed from February 2, 2020 (date of access to SEER data), to August 31, 2020. Analysis occurred from September 30, 2020, to March 30, 2021, including the primary analysis and the sensitivity calculations. The main outcome measured was accuracy of the TVUS ET threshold to accurately identify cases of EC, measured by sensitivity, negative predictive value, and area under the curve (AUC). A total of 367 073 simulated Black and White women with postmenopausal bleeding were evaluated, including 36 708 with EC. Among Black women, the currently recommended 4-mm or greater ET threshold prompted biopsy for fewer than half of EC cases (sensitivity, 47.5%; 95% CI, 46.0%-49.0%); of women referred for biopsy, 13.1% were EC cases (positive predictive value, 13.1%; 95% CI, 12.5%-13.6%). The AUC for the 4-mm or more threshold was 0.57 (95% CI, 0.56-0.57). In contrast, among the White women, the 4-mm or more threshold led to biopsy for most with EC (sensitivity, 87.9%; 95% CI, 87.6%-88.3%). Of those referred for biopsy, 14.6% had EC (positive predictive value, 14.6%; 95% CI, 14.4%-14.7%); AUC was 0.73 (95% CI, 0.73-0.74). The same variations held for the 3-mm or more and 5-mm or more ET thresholds: sensitivity, positive predictive value, and AUC were consistently lower for Black women than White women. The findings of this simulated cohort study suggest that use of ET as measured by TVUS to determine the need for EC diagnostic testing in symptomatic women may exacerbate racial disparities in EC stage at diagnosis. In simulated data, TVUS ET screening missed almost 5 times more cases of EC among Black women vs White women owing to the greater prevalence of fibroids and nonendometrioid histologic type in Black women.

Diagnostic value of different color ultrasound diagnostic method in endometrial lesions

BACKGROUNDEndometrial lesions include endometrial cancer and inferior fibroids. Among them, endometrial cancer as a malignant tumor seriously endangers the life and health of patients. Ultrasonography is an important means of diagnosing female reproductive system diseases, and it is of critical value for the early diagnosis of endometrial cancer. However, different ultrasound inspection programs have achieved different results. It is of great significance to choose a suitable inspection program.AIMTo explore the diagnostic efficacy of different ultrasonic examination methods in clinical endometrial lesions.METHODSThe 140 patients with endometrial lesions who were treated in our hospital from April 2018 to October 2019 were used as the research subjects. All patients underwent transvaginal color ultrasound and transabdominal color ultrasound. We compared the diagnostic coincidence and image display effects of the two different examination methods, and the endometrial thickness, blood flow, uterine effusion and resistance index of different diseases were observed by transvaginal color ultrasound.RESULTSThe diagnostic coincidence rate of all types of diseases of transvaginal color ultrasound was significantly higher than that of transabdominal color ultrasound (P = 0.001, 0.005, 0.001 and 0.001). In addition, the excellent and good rate of image display of transvaginal color ultrasound was higher than that of transabdominal color ultrasound (P = 0.001). There were significant differences in endometrial thickness in patients with different types of endometrial lesions through the transvaginal color examination (P = 0.001). The incidence rate of uterine effusion in patients with endometrial carcinoma was significantly higher than that in patients with other types of endometrial lesions (P = 0.001), and the rate of the blood flow was the highest (P = 0.001). The comparison of blood flow resistance index indicated that the blood flow resistance index in endometrial cancer patients was the lowest, which shows that the difference was statistically significant (P = 0.001).CONCLUSIONThe overall diagnostic efficacy of transvaginal color ultrasound in the clinical diagnosis of endometrial lesions is better than that of transabdominal color ultrasound, which held higher diagnostic coincidence rate and image display effect. There were significant differences in the thickness of the endometrium and the blood flow in different types of lesions.

Near-Infrared Fluorescent Agent for In Vitro Screening of Endometrial Cancer and Precancerous Lesions.

The lack of cytopathologists delays the advancement of screening for endometrial cancer. It was urgent to develop a new dye for rapid diagnosis. Our study aimed to synthesize a targeted folate receptor-α near-infrared (NIR) fluorescent agent, folic acid-zwitterionic NIR fluorophore (ZW-FA), and explore the feasibility for screening of endometrial cancer and precancerous change. Folic acid was conjugated with zwitterionic NIR fluorophore. The preparation of ZW-FA was validated by 1H NMR, mass spectrometric, ultraviolet spectra and fluorescence spectra. ZW-FA was incubated with endometrial cytology samples obtained from patients who underwent dilation and curettage or total hysterectomy. Diagnostic utility was calculated by applying laser confocal microscope, Image-J and statistical models, such as enumeration, receiver operating characteristic curve, logistic regression, support vector machine and decision tree were used. The purity of ZW-FA was > 95% determined by 1H NMR. ZW-FA had the strongest absorption peak at 633 nm in ultraviolet spectra. Photostability of ZW-FA was over 8 hours. In clinical validation, a total of 92 patients were enrolled. The cut-off value of ZW-FA was 49 in enumeration, which was used to distinguish the type of samples. Indicators about diagnostic utility are as follows: sensitivity 90.77%, specificity 62.96%, false-positive rate 37.04%, false-negative rate 9.23%, positive predictive value 85.51% and negative predictive value 73.91%. The samples processed by ZW-FA did not affect further Hematoxylin-Eosin staining and pathological diagnosis. It was an effective cytologic strategy for in vitro diagnosis of endometrial cancer and precancerous change by using ZW-FA.Clinical Trial Registration http://www.chictr.org.cn/index.aspx, identifier ChiCTR1800020123.

Prediction of Myometrial Invasion in Stage I Endometrial Cancer by MRI: The Influence of Surgical Diagnostic Procedure.

Simple SummaryFertility sparing treatment can be considered for young women with clinical stage 1A endometrial cancer (EC) without myometrial invasion (MI). Surgical diagnostic procedures (SDP) were needed to make diagnosis of EC, but different extents of SDP including diagnostic hysteroscopic biopsy (DHB, group 1), operative hysteroscopic partial resection (OHPR, group 2), operative hysteroscopic complete resection (OHCR, group 3), and cervical dilatation and fractional curettage (D&C, group 4) may affect the accuracy of MI assessment by magnetic resonance imaging (MRI) after SDP. Here, we retrospectively review those initially diagnosed with stage 1A EC and compare MI status on MRI reports and final histopathology of hysterectomy. We found that the MRI accuracy of MI was better in patients with EC diagnosed with D&C. Three diagnostic procedures using hysteroscopy might interfere with the diagnostic power of MI on MRI. Thus, D&C for diagnosis of EC and further hysteroscopic complete resection with hormone as a fertility sparing treatment for those confirmed as stage 1A without MI from MRI may be a choice in the future.Young women with endometrial cancer (EC) can choose fertility-sparing treatment for stage 1A disease without myometrial invasion (MI). The surgical diagnostic procedure (SDP) may affect the accuracy of magnetic resonance imaging (MRI) to assess MI. Here, we evaluated different SDP and compared the MI on MRI results with further pathologic results after hysterectomy. We retrospectively collected data on 263 patients with clinical stage IA EC diagnosed between January 2013 and December 2015. Patients were classified into four groups based on SDP, including diagnostic hysteroscopic biopsy (DHB, group 1), operative hysteroscopic partial resection (OHPR, group 2), operative hysteroscopic complete resection (OHCR, group 3), and cervical dilatation and fractional curettage (D&C, group 4). The sensitivity, specificity, diagnostic accuracy, positive predictive value, and negative predictive value of MRI to assess MI were 73.1%, 46.7%, 63.9%, 71.8%, and 48.3%, respectively. Three hysteroscopic procedures (groups 1 to 3) had a trend with a higher odds ratio of discrepancy between MRI and histopathology (p = 0.068), especially in group 2 (odds ratio 2.268, p = 0.032). Here, we found MRI accuracy of MI was better in patients with EC diagnosed with D&C. Three diagnostic procedures using hysteroscopy might interfere with the diagnostic power of MI on MRI.

Obesity increases endometrial cancer risk in Chinese women with postmenopausal bleeding.

We examined the relationship between body mass index (BMI) at referral and subsequent diagnosis of endometrial cancer in a cohort of Chinese women presenting with postmenopausal bleeding, to determine whether BMI of 25 kg/m2 would serve to delineate women at increased risk of endometrial cancer. This cohort included 4,164 Chinese women referred for postmenopausal bleeding from 2002 to 2013. For all women, a medical history was taken, and physical examination, BMI measurement, transvaginal pelvic ultrasonography, and endometrial sampling were performed. Additional investigations were performed as indicated clinically. The presence of risk factors for endometrial cancer and histological diagnoses were compared among groups defined by the standard Asian BMI cut-off values. Within the cohort, 868 (20.8%) were overweight (BMI 23-24.9 kg/m2) and 1,611 (38.7%) were obese (BMI ≥25 kg/m2), and 162 (3.9%) had endometrial cancer. The prevalence of endometrial cancer correlated with BMI category (P < 0.001). On multivariate analysis, BMI ≥25 kg/m2 was independently associated with 1.57 times risk of endometrial cancer (95% CI 1.13-2.20, P = 0.008) compared with BMI less than 25 kg/m2. When managing postmenopausal bleeding in Chinese women, the Asian BMI standard for obesity at 25 kg/m2 identified 51% of endometrial cancers in this group and denoted a 57% increased risk of endometrial cancer. Thus obesity could be used to triage women presenting with postmenopausal bleeding for prioritized investigations.

CircSLC6A6 Sponges miR-497-5p to Promote Endometrial Cancer Progression via the PI4KB/Hedgehog Axis.

Background As a new kind of noncoding RNAs, circular RNAs (circRNAs) have been substantiated to be involved in multiple biological processes. Accumulating studies indicate that circular RNAs (circRNAs) regulate the development of cancers by acting as miRNA sponges. However, the role of circRNAs in endometrial cancer (EC) is rarely reported. This study was aimed at investigating the functional roles of circSLC6A6 in EC. Methods The qRT-PCR assay was performed to detect the circSLC6A6 expression in EC tissues and cell lines. The luciferase reporter assay was performed to explore the connection between circSLC6A6 and miR-497-5p as well as the connection between miR-497-5p and PI4KB. The colony formation assay, EdU assay, wound healing assay, and transwell assay were performed to examine the proliferation, migration, and invasion of EC cells. The in vivo assay was performed to reveal the function of circSLC6A6 in tumorigenesis. Results We found that circSLC6A6 was highly expressed in both EC tissues and cells. And circSLC6A6 promoted the proliferation, migration, and invasion of EC cells in vitro. In vivo, circSLC6A6 promoted tumor growth. Besides, a mechanistic study demonstrated that circSLC6A6 could regulate tumor-associated signaling PI4KB/hedgehog pathway by sponging miR-497-5p. Conclusion This study illustrates that circSLC6A6 plays a role in promoting EC progression via the miR-497-5p-mediated PI4KB/hedgehog pathway. Our study may provide a potential novel biomarker for EC diagnosis or treatment.

Whether preoperative hysteroscopy increases the dissemination of endometrial cancer cells: A systematic review and meta-analysis.

To determine whether hysteroscopy (HSC) increases the risk of intraperitoneal dissemination in endometrial cancer patients. We conducted a comprehensive review of multiple databases. Quality assessments of eligible studies were performed using the Newcastle-Ottawa and Jadad scales. Positive peritoneal cytology (PPC) as the outcome of interest was compared between endometrial cancer patients with and without HSC. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated as a measure of effects. Three case-control studies and eight retrospective cohort studies included 3364 patients, of whom 1116 underwent preoperative HSC, which resulted in a significantly higher PPC rate (OR, 1.82; 95% CI, 1.31-2.54; p=0.0004). I2 was 11%, and the heterogeneity was acceptable. The difference between the groups with stages I-II was statistically insignificant (OR, 1.50; 95% CI, 0.75-2.99; p=0.25). When liquid was used as the uterine distension medium during HSC and the intrauterine pressure was controlled under 80 mmHg, the difference between the two groups was also insignificant (OR, 1.18; 95% CI, 0.50-2.79; p=0.71). However, when the intrauterine pressure exceeded 80 mmHg, the difference between the two groups was statistically significant (OR, 2.18; 95% CI, 1.28-3.73; p=0.004). This meta-analysis indicates that preoperative HSC in patients with endometrial cancer may increase the risk of intraperitoneal dissemination of malignant cells, which may be associated with intrauterine pressure >80 mmHg but not with stages I-II. There is no reason to avoid HSC for the diagnosis of endometrial cancer, especially in early stages, but intrauterine pressure should possibly be controlled below 80 mmHg.

Three plasma-based microRNAs as potent diagnostic biomarkers for endometrial cancer.

MicroRNAs (miRNAs), with noticeable stability and unique expression pattern in plasma of patients with various diseases, are powerful non-invasive biomarkers for cancer detection including endometrial cancer (EC). The objective of this study was to identify promising miRNA biomarkers in plasma to assist the clinical screening of EC. A total of 93 EC and 79 normal control (NC) plasma samples were analyzed using Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) in this four-stage experiment. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic value. Additionally, the expression features of the identified miRNAs were further explored in tissues and plasma exosomes samples. The expression of miR-142-3p, miR-146a-5p, and miR-151a-5p was significantly overexpressed in the plasma of EC patients compared with NCs. Areas under the ROC curve of the 3-miRNA signature were 0.729, 0.751, and 0.789 for the training, testing, and external validation phases, respectively. The diagnostic performance of the identified signature proved to be stable in the three public datasets and superior to the other miRNA biomarkers in EC diagnosis. Moreover, the expression of miR-151a-5p was significantly elevated in EC plasma exosomes. A signature consisting of 3 plasma miRNAs was identified and showed potential for the non-invasive diagnosis of EC.

Immune infiltration-related N6-methyladenosine RNA methylation regulators influence the malignancy and prognosis of endometrial cancer.

N6-methyladenosine (m6A) RNA methylation is associated with malignant tumor progression and is modulated by various m6A RNA methylation regulator proteins. However, its role in endometrial cancer is unclear. In this work, we analyzed sequence, copy number variation, and clinical data obtained from the TCGA database. Expression was validated using real-time quantitative polymerase chain reaction and immunohistochemistry. Changes in m6A RNA methylation regulators were closely related to the clinicopathological stage and prognosis of endometrial cancer. In particular, ZC3H13, YTHDC1, and METTL14 were identified as potential markers for endometrial cancer diagnosis and prognosis. The TIMER algorithm indicated that immune cell infiltration correlated with changes in ZC3H13, YTHDC1, and METTL14 expression. Meanwhile, ZC3H13 or YTHDC1 knockdown promoted the proliferation and invasion of endometrial cancer cells. Through gene enrichment analysis, we constructed a regulatory network in order to explore the potential molecular mechanism involving ZC3H13, YTHDC1, and METTL14. Virtual screening predicted interactions of potential therapeutic compounds with METTL14 and YTHDC1. These findings advance the understanding of RNA epigenetic modifications in endometrial cancer while identifying m6A regulators associated with immune infiltration, prognosis, and potential treatment strategies.

MicroRNA expression profile in serum reveals novel diagnostic biomarkers for endometrial cancer.

Purpose: Circulating microRNAs (miRNAs) prove to be promising diagnostic biomarkers for various cancers, including endometrial cancer (EC). The present study aims to identify serum microRNAs that can serve as potential biomarkers for EC diagnosis.Patients and methods: A total of 92 EC and 102 normal control (NC) serum samples were analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) in this four-phase experiment. The logistic regression method was used to construct a diagnostic model based on the differentially expressed miRNAs in serum. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value. To further validate the diagnostic capacity of the identified signature, the 6-miRNA marker was compared with previously reported biomarkers and verified in three public datasets. In addition, the expression characteristics of the identified miRNAs were further explored in tissue and serum exosomes samples.Results: Six miRNAs (miR-143-3p, miR-195-5p, miR-20b-5p, miR-204-5p, miR-423-3p, and miR-484) were significantly overexpressed in the serum of EC compared with NCs. Areas under the ROC of the 6-miRNA signatures were 0.748, 0.833, and 0.967 for the training, testing, and the external validation phases, respectively. The identified signature has a very stable diagnostic performance in the large cohorts of three public datasets. Compared with previously identified miRNA biomarkers, the 6-miRNA signature in the present study has superior performance in diagnosing EC. Moreover, the expression of miR-143-3p and miR-195-5p in tissues and the expression of miR-20b-5p in serum exosomes were consistent with those in serum.Conclusions: We established a 6-miRNA signature in serum and they could function as potential non-invasive biomarker for EC diagnosis.

The Clinical Significance of DJ1 and L1CAM Serum Level Monitoring in Patients with Endometrial Cancer.

Circulating tumor markers are not routinely used in patients with endometrial cancer (EC). This pilot study evaluated the role of monitoring new biomarkers DJ1 and L1CAM, in correlation with CA125 and HE4, for the effects of anticancer treatment and preoperative management in EC patients. Serial serum levels of DJ1, L1CAM, CA125 and HE4 were collected in 65 enrolled patients. Serum DJ1, L1CAM, CA125 and HE4 levels were significantly higher at the time of diagnosis compared to those measured during follow-up (FU). In patients with recurrent disease, serum DJ1, CA125 and HE4 levels were significantly higher at the time of recurrence compared to levels in disease-free patients. Serum L1CAM levels were also higher in patients with recurrence but without reaching statistical significance. While DJ1 levels were not affected by any of the observed patient-related characteristics, L1CAM levels were significantly higher in patients with age ≥60 years who were overweight. At the time of EC diagnosis, DJ1 and L1CAM serum levels did not correlate with stage, histological type or risk of recurrence. This is a preliminary description of the potential of serial DJ1 and L1CAM serum level measurement for monitoring the effects of treatment in EC patients.

“Identification and characterization of endometrial carcinoma with tumor markers HE4 and CA125 in serum and endometrial tissue samples and systematic review of the literature”

Diagnosis of endometrial cancer (EC) is made by biopsy sampling with pathological analysis, but it is extremely important to make an accurate diagnosis in order to plan the specific treatment. We hypothesized that human epididymis protein 4 (HE4) in endometrial tissue and in serum could be beneficial for a more precise diagnosis. This prospective study compared patients with EC against non- EC, matched through several variables. The inclusion criteria were: females older than 18 years who accepted to participate; who had never undergone surgery for other oncological pathologies (ovarian, colon, cervical carcinoma or uterine sarcoma); none of them had received preoperative chemo- or radio-therapy; and no participant had any severe renal or liver pathology. All had pre-surgery blood sampling and then underwent hysterectomy. Histopathological assessment of endometrial samples was made by a pathologist who compared normal histopathological staining with HE4-antibody staining. In total there were 34 cases and 35 controls recruited. There was poor correlation between tissue HE4 in patients with and without carcinoma. However, serum HE4 was significant for the diagnosis of endometrial carcinoma (median EC: 123.1 U, median NE: 64.67 U, p=0.002), although the carbohydrate antigen 125 level was not significant (p=0.208). The findings concerning the utility of HE4 contrast with earlier reports. However, the conclusions for serum measurements are positive and suggest that the tumor marker HE4 seems to be able to diagnose EC.

Transvaginal Real-Time Shear Wave Elastography in the Diagnosis of Endometrial Lesions.

BackgroundTo explore the value of transvaginal real-time shear wave elastography (SWE) in the diagnosis of endometrial lesions.MethodsA total of 140 female patients with endometrial lesions, confirmed by pathological results, were divided into three groups: 45 cases of endometrial polyps, 29 cases of endometrial hyperplasia and 66 cases of endometrial cancer. A total of 100 cases of normal endometrium were used as the control group, including 52 cases in the proliferative stage and 48 cases in the secretory stage. Transvaginal real-time shear wave elastography was performed in all four groups.ResultsEmean, Emax and Esd were expressed as the average standard deviation. Among the control group, the results were 26.24±9.74, 38.09±9.18, and 4.25±2.73 kPa, respectively, in the proliferative endometrium cases and 12.51±7.46, 27.22±11.32, 4.40±2.52 kPa, respectively, in the secretory endometrium cases. Among the experimental group, the result was 15.68±8.18, 27.28±10.28 and 3.62±1.81 kPa respectively in the endometrial polyps cases; 21.20 ± 12.57, 36.32 ± 15.04, and 5.09 ±3.93 kPa in the endometrial hyperplasia cases; 49.36±25.51, 86.66±42.27 and 14.86±10.63 kPa in the endometrial cancer cases. The difference was statistically significant (P <0.05). When the truncation values of Emean, Emax and Esd were 28.50, 52.45 and 9.05 kPa, respectively, to distinguish between normal endometrium and endometrial cancer, Emax has the highest diagnostic value.ConclusionReal-time SWE technology might be used as an auxiliary method in the diagnosis and differential diagnosis of endometrial cancer. More quantitative indicators are conducive to diagnosis.

Assessment of Modifiable Factors for the Association of Marital Status With Cancer-Specific Survival

Married patients with cancer have better cancer-specific survival than unmarried patients. Increasing the early diagnosis and definitive treatment of cancer among unmarried patients may reduce the survival gap. To evaluate the extent to which marriage is associated with cancer-specific survival, stage at diagnosis, and treatment among patients with 9 common solid cancers and to recommend methods for reducing the survival gap. This retrospective, population-based cohort study included patients older than 18 years who were diagnosed with 1 of 9 common cancers between January 1, 2007, and December 31, 2016. Patient data were retrieved from the Surveillance, Epidemiology, and End Results Program. Statistical analyses were performed from August 1 to October 1, 2020. Marital status, classified as married and unmarried (including single, separated, divorced, widowed, and unmarried patients or domestic partners). The primary outcome was the time ratio (TR) of cancer-specific survival (married vs unmarried). Mediation analyses were conducted to determine the extent to which the association of marriage with cancer-specific survival was mediated by stage at diagnosis and treatment. This study included 1 733 906 patients (894 379 [51.6%] women; 1 067 726 [61.6%] married; mean [SD] age, 63.76 [12.60] years). Multivariate analyses found that those who were married were associated with better cancer-specific survival than unmarried patients (TR, 1.36; 95% CI, 1.35-1.37). Early diagnosis in breast cancer, colorectal cancer, endometrial cancer, and melanoma mediated the association between marital status and cancer-specific survival (breast cancer: proportion mediated [PM], 11.4%; 95% CI, 11.2%-11.6%; colorectal cancer: PM, 10.9%; 95% CI, 10.7%-11.2%; endometrial cancer: PM, 12.9%; 95% CI, 12.5%-13.3%; melanoma: PM, 12.0%; 95% CI, 11.7-12.4%). Surgery mediated the association between marital status and cancer-specific survival in lung (PM, 52.2%; 95% CI, 51.9%-52.4%), pancreatic (PM, 28.9%; 95% CI, 28.6%-29.3%), and prostate (PM, 39.3%; 95% CI, 39.0%-39.6%) cancers. Chemotherapy mediated the association of marital status with cancer-specific survival in lung (PM, 37.7%; 95% CI, 37.6%-37.9%) and pancreatic (PM, 28.6%; 95% CI, 28.4%-28.9%) cancers. Improved cancer-specific survival associated with marriage was greater among men than women (men: TR, 1.27; 95% CI, 1.25-1.28; women: TR, 1.20; 95% CI, 1.19-1.21). The contribution of receiving an early diagnosis and treatment with surgery or chemotherapy to the association between marital status and cancer-specific survival was greater among men than women (early diagnosis: PM, 21.7% [95% CI, 21.5%-21.9%] vs PM, 20.3% [95% CI, 20.2%-20.4%]; surgery: PM, 26.6% [95% CI, 26.4%-26.7%] vs PM, 11.1% [95% CI, 11.0%-11.2%]; chemotherapy: PM, 6.8% [95% CI, 6.7%-6.8%] vs PM, 5.1% [95% CI, 5.0%-5.2%]). In this study, survival disparities associated with marital status were attributable to early diagnosis in breast, colorectal, and endometrial cancers as well as melanoma and to treatment-related variables in lung, pancreatic, and prostate cancers. The findings also suggest that marriage may play a greater protective role in the cancer-specific survival of men than of women.

Mismatch repair gene alteration subtypes impact age of onset of mismatch repair-deficient cancers.

10521 Background: This study investigated whether mismatch repair (MMR) gene alterations and alteration subtypes impacted age at onset of MMR-deficient cancers. Methods: A retrospective study of association of MMR-deficient alterations and age of onset of MMR-deficient lung, breast, prostate, bladder, colorectal, endometrial, and/or ovarian cancers was conducted by using cBIPORTAL dataset. Results: A total of 815 participants with MMR-deficient alterations were enrolled, 346 males and 469 females (median age 63 years; age range, 20-90 years). Males were diagnosed as colorectal and bladder cancer at later ages than females. When stratified by alteration type, individuals with MSH6 or PMS2 missense alterations had later ages of onset of colorectal cancer than those with no missense alterations. Participants with MSH2 AMP alterations were older at the diagnosis of endometrial cancer than those without MSH2 AMP alterations. Females with MLH1 missense alterations had later ages of onset of ovarian cancer than those with no missense alterations. Individuals with PMS2 AMP alterations were confirmed with lung cancer at later ages than those with no PMS2 AMP alterations. Carriers with MSH6or PMS2 missense alterations were older at the time of diagnosis of prostate cancer than those with no missense alterations. Conclusions: Gene alterations and subtype of alterations could stratify carriers with MMR-deficiency in bespoke surveillance. The mechanism of the association of MMR-deficient alterations and alteration subtypes and age at the diagnosis of MMR-deficient cancers needs to be further study.[Table: see text]

Risk and distribution of venous thromboembolic events during treatment for advanced endometrial cancer.

e17565 Background: Understanding the incidence and timing of venous thromboembolic (VTE) events among patients receiving treatment for advanced endometrial cancer (EC) may help to inform VTE risk stratification and consideration of thromboprophylaxis. We aimed to describe the rate of VTE at each stage of primary treatment for advanced EC as well as the baseline Khorana Score (KS) distribution in this population. Methods: This was a retrospective cohort study of patients diagnosed with stage IVB EC from January 2001 to July 2020 at a single academic institution. The primary outcome was VTE incidence at each stage of primary treatment (at diagnosis, during neoadjuvant chemotherapy [NACT] if applicable, post-operatively [&lt; 30 days from surgery], or during adjuvant chemotherapy). Subjects who were anticoagulated at EC diagnosis were excluded. Khorana score was calculated according to established parameters (1 point each for gynecologic malignancy, pre-chemotherapy platelet count ≥ 350, hemoglobin &lt; 10 or use of red blood cell growth factors, leukocyte count &gt;11, and BMI ≥ 35). Descriptive statistics were used for analysis. Results: There were 76 patients diagnosed with stage IVB EC, 2 of whom were excluded for anticoagulation at cancer diagnosis. Of the remaining 74 patients, 58 underwent primary surgery (78%) and 16 received NACT (22%). A total of 59 received adjuvant chemotherapy after either primary or interval debulking surgery. The two predominant tumor histologies were serous (48%) and endometrioid (20%).A total of 16 VTE occurred during the primary treatment course (22%), 11 among the cohort receiving primary surgery (19%) and 5 among the cohort receiving NACT (31%). The distribution of VTE by stage of primary treatment is shown in Table. The rate of VTE was highest during adjuvant chemotherapy. There were 62 patients for whom a Khorana score could be calculated either before NACT or adjuvant chemotherapy. The distribution of KS was: 17 (27%) with KS 1 (low risk) and 45 (73%) with KS ≥ 2 (intermediate – high risk). Of the 11 non-postoperative VTE, 3 patients (27%) had KS 1 and 8 (73%) had KS ≥ 2. Conclusions: The incidence of VTE among patients with advanced EC was high regardless of whether treatment was initiated with NACT or primary surgery. The majority of VTE occurred among patients with a high KS, but those with a low KS remained at risk. Thromboprophylaxis among all patients with advanced EC may be warranted, and larger studies are needed to determine the performance of KS as a VTE predictor in advanced EC.[Table: see text]