Diagnosis Of Endometrial Carcinoma Research Articles

Мodern methods of diagnosis of endometrial carcinoma

The main methods of histological diagnosis of endometrial carcinoma are dilatation and curettage, fractional curettage, and diagnostic hysteroscopy with endometrial biopsy. This retrospective study aims to compare the preoperative histological results obtained by different diagnostic methods with the postoperative ones in patients with endometrial carcinoma and determine the most accurate and safest method for diagnosing the disease. From 06.2020 to 09.2023, a retrospective study was conducted on 80 patients with histologically proven carcinoma of the endometrium, treated at University Hospital Saint Marina-Pleven. The mean age of the patients was 58.04 ± 10.46, ranging from 28 to 78. The comparative analysis of the discrepancies of the histological verification methods in the evaluation of the preoperative and postoperative histological result showed that a statistically significantly higher percentage of discrepancies (19.5%) had the dilatation and curettage compared to the zero discrepancy of the hysteroscopy (0.0%). The relative proportion of discrepancies of the fractional curettage is 14.3%. The cytological result was negative for tumor cells in 97.5% and positive in 2.5%. In all patients with a positive cytological result for tumor cells, the method of histological verification was dilatation and curettage. Performing diagnostic hysteroscopy and observing safety principles such as creating low intrauterine pressure and short operative time is a safe and reliable method for diagnosing endometrial carcinoma.

Analysis of characteristics of peripheral blood lymphocytes in endometrial carcinoma: a single-center study based on five-year clinical data

IntroductionThis study analyzed and discussed the characteristics of peripheral blood lymphocytes (PBLs) in patients with endometrial carcinoma (EC) to explore the PBLs’ clinical application value.MethodsThis single-center case‒control study analyzed the clinical data of patients with EC and uterine fibroids who underwent surgery at the First Affiliated Hospital of Chongqing Medical University between October 2018 and October 2023 retrospectively. The Center for Clinical Molecular Medical Detection of our hospital performed PBLs detection using flow cytometry, and recorded the detection results in the electronic medical records system. Between-group and subgroup comparisons of PBLs in patients with EC were analyzed using t-test or Mann–Whitney U test. The effect of surgery on PBLs in patients with EC was assessed using a paired t-test or the Wilcoxon signed rank test.ResultsThe immune function of patients with EC was significantly lower than that of healthy people (P < 0.05) and those with benign uterine diseases (P < 0.05) and was related to body mass index (BMI), hypertension, diabetes, and blood lipids (P < 0.05). In patients with EC, the PBLs counts decreased significantly after surgery (P < 0.05) and more kinds of lymphocytes were affected in the laparoscopic surgery group than in the open surgery group.ConclusionsWith the decrease of PBLs counts, the immune status of patients with EC is impaired. Metabolic syndrome (Mets), including obesity, hypertension, diabetes, and high blood lipids, also affects the immune function of patients with EC. And for EC patients, the effect of laparoscopic surgery is greater than that of open surgery. PBLs has the potential to be one of indicator during the diagnosis and treatment of EC.Trial registrationThis study was retrospectively registered by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (approval number K2023-578).

Combination of circulating tumor cells, lncRNAs and DNA methylation for the diagnosis of endometrial carcinoma.

Endometrial carcinoma (EC) is one of the most common gynecological malignant neoplasms, the prognosis of which is strongly related to the time of diagnosis, with an earlier diagnosis leading to a better prognosis. Therefore, effective diagnostic indicators and methods are needed to ensure early detection. The present study explored the following in EC: Circulating tumor cells (CTCs); the long noncoding RNAs (lncRNAs) RP4-616B8.5, RP11-389G6.3 and carboxy-terminal domain (CTD)-2377D24.6; and the methylation of cysteine dioxygenase type 1 (CDO1) and CUGBP Elav-like family member 4 (CELF4). In total, 85 patients, including 71 with EC, and 14 without EC (NO-EC) but with uterine fibroids or polyps, were included in the present study. In total, 46 patients with EC and 8 NO-EC patients underwent CTC detection. In the evaluation of the EC vs. NO-EC groups, the results showed that the CTC-positive rate of the EC group was 80.43% and that the area under the curve (AUC) value of CTCs was 0.8872 (P=0.0098). A total of 35 patients with EC and 14 NO-EC patients underwent detection of the RP4-616B8.5, RP11-389G6.3 and CTD-2377D24.6 lncRNAs. When the levels of the three lncRNAs RP4-616B8.5, RP11-389G6.3 and CTD-2377D24.6 were compared between the EC and NO-EC groups, they were higher in the EC group; the P-values were 0.0002, 0.0001 and <0.0001, respectively, and the AUC values were 0.8184, 0.8347 and 0.8265, respectively. In addition, a total of 35 patients with EC and 8 NO-EC patients underwent CDO1 and CELF4 DNA methylation analysis. The positive rates of the methylated genes CDO1 and CELF4 were 20% (7/35) and 5.71% (2/35), and the P-values of the comparisons between the EC and NO-EC groups were 0.1748 and 0.5004, respectively; the AUC values were 0.6000 and 0.5286. Furthermore, the combination of CTCs, and lncRNAs RP4-616B8.5, RP11-389G6.3 and CTD-2377D24.6 exhibited high performance in the detection of EC (AUC=0.9375).

Screening for ferroptosis genes related to endometrial carcinoma and predicting of targeted drugs based on bioinformatics.

Endometrial carcinoma is one of most common malignant tumors in women, and ferroptosis is closely related to the development and treatment of endometrial carcinoma. The aim of this study was to screen ferroptosis-related genes associated with endometrial carcinoma and predict targeted drugs through bioinformatics. 761 differentially expressed genes were obtained by the dataset GSE63678 from the GEO database, and most of the genes were enriched in the KEGG_CELL_CYCLE and KEGG_OOCYTE_MEIOSIS signaling pathways. 22 ferroptosis-differentially expressed genes were obtained by intersection with the FerrDb database. These genes were involved in biological processes including macromolecular complex assembly and others, and involved in signal pathways including glutathione metabolism, p53 signaling pathway and others. CDKN2A, IDH1, NRAS, TFRC and GOT1 were obtained as hub genes by PPI network analysis. GEPIA showed that CDKN2A, IDH1, NRAS and TFRC were significantly expressed in endometrial carcinoma. Immunohistochemical results showed that CDKN2A, NRAS and TFRC were significantly expressed in endometrial carcinoma clinical tissue samples. The ROC constructed by TCGA database showed that CDKN2A, NRAS and TFRC had significant value in the diagnosis of endometrial carcinoma, and all had prognostic efficacy. 136,572-09-3 BOSS and others were identified as potential targeted drugs for endometrial carcinoma targeting ferroptosis. Our study has shown that ferroptosis-related genes CDKN2A, NRAS and TFRC are diagnostic markers of endometrial carcinoma, and 136,572-09-3 BOSS, methyprylon BOSS, daunorubicin CTD 00005752, nitroglycerin BOSS and dUTP BOSS, IRON BOSS, Imatinib mesylate BOSS, 2-Butanone BOSS, water BOSS, and L-thyroxine BOSS may be potential therapeutic drugs.

Potential application of body fluids autofluorescence in the non-invasive diagnosis of endometrial cancer.

Endometrial carcinoma (EC) is the most common cancer of the female reproductive tract in developed countries. The prognosis and 5-year survival rates are closely tied to the stage diagnosis. Current routine diagnostic methods of EC are either lacking specificity or are uncomfortable, invasive and painful for the patient. As of now, the gold diagnostic standard is endometrial biopsy. Early and non-invasive diagnosis of EC requires the identification of new biomarkers of disease and a screening test applicable to routine laboratory diagnostics. The application of untargeted metabolomics combined with artificial intelligence and biostatistics tools has the potential to qualitatively and quantitatively represent the metabolome, but its introduction into routine diagnostics is currently unrealistic due to the financial, time and interpretation challenges. Fluorescence spectral analysis of body fluids utilizes autofluorescence of certain metabolites to define the composition of the metabolome under physiological conditions. This review highlights the potential of fluorescence spectroscopy in the early detection of EC. Data obtained by three-dimensional fluorescence spectroscopy define the quantitative and qualitative composition of the complex fluorescent metabolome and are useful for identifying biochemical metabolic changes associated with endometrial carcinogenesis. Autofluorescence of biological fluids has the prospect of providing new molecular markers of EC. By integrating machine learning and artificial intelligence algorithms in the data analysis of the fluorescent metabolome, this technique has great potential to be implemented in routine laboratory diagnostics.

Abstract 7312: Construction of a gene panel for liquid biopsy-based diagnostics of gynecologic cancer

Abstract Background: Ovarian carcinoma (OC) is the leading cause of death from gynecologic cancers mainly due to late detection, where most patients are diagnosed at advanced stages (51% in stage III; 29% in stage IV). Despite an overall more favorable prognosis, endometrial carcinoma (EC) is the most common gynecologic cancer, with an increasing incidence and where some subtypes are associated with a poor prognosis. Identification of DNA mutations from precancerous lesions or early-stage OC and EC would allow for early intervention. Liquid biopsies through routine sampling such as endocervical sampling, or blood collection for isolation and analysis of ctDNA have previously been assessed for their use in detection of OC and EC. These studies have provided evidence that tumor-derived mutations can be detected in endocervical samples, supporting endocervical liquid biopsies as a potential source of ctDNA. Herein, we aimed to construct a diagnostic gene panel corresponding to common mutation profiles of OC and EC to detect early-stage malignancy through a non-invasive approach. Methods: Using the NGS-method, Simple multiplexed PCR-based barcoding of DNA for sensitive mutation detection using sequencing (SiMSen-Seq), a gene panel was constructed targeting hotspot mutations in known OC- and EC-associated genes. Hotspots were identified using the Catalogue of Somatic Mutations in Cancer (COSMIC) database or retrieved from the literature and assays were designed for amplification of short DNA fragments. Precise assay development was carried out including multiple steps of careful validation to ensure high specificity and efficient amplification. Individual assays were validated in multiple steps using qPCR and fragment analysis. Results: The gene panel was designed as two non-overlapping subunits for comprehensive diagnosis of OC and EC. The two constructed multiplexes, together composed of 125 single assays target genomic regions in 34 EC and OC-associated genes e.g., PTEN, TP53, PIK3CA and CTNNB1. Included assays had a median amplicon size of 92 bp (range 57-111 bp). Both multiplexes displayed good performance with distinguishable libraries at low DNA input (10 ng). Validation of individual assays showed high specificity and efficient amplification where &amp;gt;80% of assays displayed a sequencing coverage &amp;gt;500 UMI counts at a consensus depth of 3. Patient coverage calculations of COSMIC data suggested comparable coverage as similar published approaches. Conclusion: The results suggest that the constructed gene panel has great potential to detect mutations in liquid biopsies collected from the gynecologic tract, despite low tumor DNA levels. Validation of the two multiplexes by fragment analysis and sequencing showed high performance, hence, prospective for the approaching sequencing of liquid biopsies. Citation Format: Sara Schumacher, Therese Carlsson, Jacob Malchau Lauesgaard, Anna Linder, Amanda Olsson Widjaja, Karin Sundfeldt. Construction of a gene panel for liquid biopsy-based diagnostics of gynecologic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7312.

Abstract IA002: Management of newly diagnosed endometrial cancers and molecular classification

Abstract In the past 50 years, the treatment of this cancer has evolved from a regimen of preoperative radiation therapy followed by hysterectomy, to individualized management consisting of surgical treatment with or without additional therapy depending on whether various risk factors are identified. After the diagnosis of endometrial carcinoma has been histologically confirmed, uterine and extrauterine risk factors affect the probability of retroperitoneal lymph node involvement and subsequent survival. Surgical staging is a critical component for the proper diagnosis and management of all endometrial carcinomas. FIGO stage is the most powerful predictor of prognosis. Surgical staging is feasible by minimally invasive techniques. Patients with significant medical comorbidities who are not acceptable candidates for surgery may be managed by alternative means. Women with EC are diagnosed under the age of 40 may be eligibile for nonoperative management if there is no clear evidence of myometrial invasion. As the contemporary management of EC continues to evolve, and the indications for lymph node dissection remain controversial. Minimally invasive management of EC has increasingly been integrated into standard practice. In 2006, The Cancer Genome Atlas (TCGA) began with studies in glioblastoma and high-grade serous ovarian cancer. The National Institutes of Health committed major resources to TCGA to collect and characterize the genomic landscape of more than 20 cancer types. In 2013, TCGA published findings for endometrial cancers. Only serous and endometrioid subtypes were accrued in the endometrial cancer project. TCGA has reclassified endometrioid and serous endometrial cancers in four broad categories using comprehensive genomic approaches. One-third of the cancers is characterized by microsatellite instability (MSI) and associated hyper-mutation. The cancers without MSI can be further separated into two groups. Serous cases with extensive DNA copy number alterations and genomic instability comprise one group, and endometrioid cases with few or only focal copy number alterations comprise the other. A smaller fourth sub-group contains samples with very high mutation rates and is characterized by mutations in POLE. Molecular features can be distinctly overlaid onto these four sub-classifications, and each have important clinical implications that are currently being used in both clinical practice and clinical trial design. In this educational presentation, we will discuss the management of newly diagnosed endometrial cancers, review the molecular classification of endometrial cancers, and identify approaches that incorporate these findings into clinical care and clinical trial design. Citation Format: Douglas A. Levine. Management of newly diagnosed endometrial cancers and molecular classification [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA002.

Impact of obesity in the identification of the sentinel lymph node in endometrial cancer: a retrospective, monocentric study and literature review

PurposeTo evaluate the sentinel lymph node (SLN) protocol for staging endometrial carcinomas, assessing its impact on surgical management, and determining indications for adjuvant therapies. The study also examines factors that may influence SNL mapping, particularly focusing on the failure of the technique due to obesity.MethodsA retrospective analysis was conducted on the medical records of patients with a histological diagnosis of endometrial carcinoma, who underwent surgical staging with SLN biopsy. The lymph node status was compared between non-obese (group 1) and obese (group 2) patients.Results71 women were included in the study, of which 33 were non-obese (46.5%) and 38 were obese (53.5%). The failure detection rate was higher in obese patients (14, 36.8%) compared to non-obese patients (5, 15.2%) (p = 0.039). The risk of mapping failure increased by 1.6 times for every 5-unit increase in body mass index (BMI) (OR 1.672, 95% CI 1.024–2.730, p = 0.040). BMI was confirmed as an independent risk factor for mapping failure in both univariate (OR 3.267, 95% CI 1.027–10.395, p = 0.045) and multivariate analyses (OR 5.779, 95% CI 1.320–25.297, p = 0.020).ConclusionSLN detection in obese patients requires great care, as obesity may alter the sensitivity of the technique.

Function of homocysteine and HE4 in endometrial carcinoma: verified by prospective experiment.

Timely diagnosis is the key factor to improve the prognosis of endometrial carcinoma (EC). To date, no particularly good markers could significantly improve the detection rate of EC. This study aimed to assess the utility of serum markers homocysteine (Hcy), human epididymal protein 4 (HE4), cancer antigen 199 (CA199), cancer antigen 125 (CA125), fibrinogen (Fib), and D-dimer (D-D) for EC diagnosis, especially Hcy of which its role in EC has not been noticed. Pre-test and verification tests were performed. In Pre-test, the diagnostic value of the included markers was evaluated and the right marker was chosen to establish an efficient new risk index for screening EC. In verification tests, the applicability of the new risk index was tested. Several evaluation indices including receiver operating characteristic (ROC) curve, Youden Index, sensitivity (SN), and specificity (SP), were adopted to assess the diagnostic value of the included markers for EC. Hcy may be useful in the diagnosis of EC. Its diagnostic value was not significantly lower than that of HE4. Based on the diagnostic value of Hcy and HE4, a new risk index was established, which demonstrated high value in EC diagnosis (ROC, 0.801), especially among young female patients (age ≤50 years, ROC, 0.871). Furthermore, the level of Hcy, but not HE4, was notably different in normal or benign endometrial lesions, atypical endometrial hyperplasia (AEH), and EC. The change of Hcy levels could be used to diagnose EC and when taken into consideration together with the detection of HE4, the diagnostic accuracy of EC is further improved.

EXOSC5 maintains cancer stem cell activity in endometrial cancer by regulating the NTN4/integrin β1 signalling axis.

Endometrial carcinoma (EC) is a common type of uterine cancer in developed countries, originating from the uterine epithelium. The incidence rate of EC in Taiwan has doubled from 2005. Cancer stem cells (CSCs) are a subpopulation of cancer cells that have high tumorigenicity and play a crucial role in the malignant processes of cancer. Targeting molecules associated with CSCs is essential for effective cancer treatments. This study delves into the role of Exosome component 5 (EXOSC5) in EC. Data from The Cancer Genome Atlas suggests a correlation between high EXOSC5 mRNA expression and unfavorable EC prognosis. EXOSC5 knockdown diminished EC-CSC self-renewal and reduced expression of key cancer stemness proteins, including c-MYC and SOX2. Intriguingly, this knockdown significantly curtailed tumorigenicity and CSC frequency in EC tumor spheres. A mechanistic examination revealed a reduction in netrin4 (NTN4) levels in EXOSC5-depleted EC cells. Moreover, NTN4 treatment amplified EC cell CSC activity and, when secreted, NTN4 partnered with integrin β1, subsequently triggering the FAK/SRC axis to elevate c-MYC activity. A clear positive relation between EXOSC5 and NTN4 was evident in 93 EC tissues. In conclusion, EXOSC5 augments NTN4 expression, activating c-MYC via the integrin β1/FAK/SRC pathway, offering potential avenues for EC diagnosis and treatment.

Vaginal hysterectomy for the treatment of low-risk endometrial cancer: Surgical technique, costs, and perioperative and oncologic results

ObjectivesThis study aimed to describe an operative technique for vaginal hysterectomy (VH) and assess the costs, perioperative, and oncological outcomes for this procedure when used in the treatment of patients with low-risk endometrial cancer (LREC). MethodsA retrospective analysis of medical records was conducted on patients who underwent VH to treat precursor and invasive endometrial lesions between April 2019 and November 2021 at a single center in São Paulo, Brazil. ResultsThirty-four patients met the inclusion criteria. The mean patient age was 61.9 years, and the mean body mass index (BMI) was 34. Obese patients (BMI ≥ 30) accounted for 77% of the sample. Preoperative functional capacity measures were Eastern Cooperative Oncology Group (ECOG) 0–1 and ECOG-2 for 91% and 9% of the patients, respectively. The mean operative time and length of hospital stay were 109 min and 1.2 days, respectively. Four patients had a conversion of the surgical route to laparotomy. No major intraoperative complications were observed. Patients who underwent surgical conversion had a greater uterine volume (227 versus 107 mL, p = 0.006) and longer operative time (177 versus 96 min, p = 0.001). The total cost associated with VH was, on average, US$ 2058.77 (R$ 10,925.91), representing 47% of the cost associated with non-vaginal routes. Twenty-eight patients received a definitive diagnosis of endometrial carcinoma; of these, three received adjuvant radiotherapy. The mean follow-up period was 34.6 months for the patients diagnosed with cancer. One case of disease recurrence occurred 16.6 months after surgery, with one death at 28.6 months of follow-up. ConclusionsThese findings suggest that VH could be a feasible and cost-effective alternative for selected patients with LREC in low-resource settings.

Keratinization in atypical glandular cell clusters as a cytological clue to endometrioid carcinoma on cervical cytology.

Specific diagnosis of endometrial carcinomas on cervical cytology is difficult with few useful cytomorphological clues reported. This study reviews a cohort of cervical cytology to investigate the presence of keratinization in atypical glandular cells (AGC), an undescribed cytomorphological clue for identifying endometrial endometrioid carcinomas on cervical cytology. Cervical cytology slides from patients with a histologic diagnosis of endometrial endometrioid carcinoma were reviewed for the presence of keratinization associated with AGCs. Corresponding histology slides were reviewed for tumour grading and degree of squamous differentiation. In total, 42 cases of cervical cytology specimens from 41 patients were retrieved, including 7 (16.7%) with keratinization associated with AGCs seen and 35 (83.3%) without. Comparison of histologic grading did not demonstrate an association with the presence of keratinization on cytology (p = 0.565). Corresponding histology slides were available for 37 cases. Cytologic and histologic keratinization were associated statistically (p = 0.002). Frank keratinization was seen on histologic slides of five cases, with four also showing cytologic keratinization. Area of squamous differentiation, including squamous morule formation, did not correlate with keratinization on cytologic preparation (p = 0.185). Histologic and cytologic keratinization are observed in endometrioid endometrial carcinomas. Such is reflected in cervical cytology by the presence of orangeophilic, rigid and acellular fragments within or associated with AGC clusters. Keratinization, when identified with AGCs, should be regarded as a cytologic clue suggestive of an endometroid carcinoma of endometrial origin.

The value of T2 mapping for evaluating the pathological type, grade and depth of myometrial invasion in endometrial carcinoma

Objective: To investigate the value of T2 map and synthetic T2WI generated by T2 mapping in evaluating the histological type, pathological classification and depth of myometrial invasion of endometrial carcinoma (EC). Methods: Seventy-three patients with pathologically proven EC diagnosed at the First Affiliated Hospital of Zhengzhou University from December 2019 to December 2021 and 42 healthy volunteers were enrolled in the study. All subjects underwent conventional MRI, diffusion weighted imaging (DWI) and T2 mapping sequence for the pelvic cavity to test the T2 values and the apparent diffusion coefficient (ADC) of the focus nidus of the patients and the normal endometrium of the volunteers. The T2 and ADC values of EC vs normal endometrium, and those of different histological types and pathological grades were compared. The receiver operating characteristic (ROC) curves were constructed to evaluate the diagnostic performance of T2 and ADC values in determining the pathological type and classification of EC. In addition, two radiologists used synthetic T2WI combined with T2 map and conventional T2WI combined with DWI, respectively, to evaluate the depth of myometrial invasion, and compared the imaging results with the results of pathological diagnosis to evaluate the diagnostic efficacy of the two methods in determining the depth of myometrial invasion. Results: The T2 and ADC values of endometrial carcinoma were 85.0 (80.8, 92.5) ms and 0.71 (0.64, 0.77) ×10(-3) mm(2)/s, respectively, which were significantly lower than those of normal endometrium [147.4 (123.4, 176.7) ms and 1.46 (1.26, 1.76)×10(-3) mm(2)/s, respectively; both P<0.05]. The T2 values of endometrioid carcinoma (EA) [84.1 (79.5, 88.7) ms] were significantly lower than those of non-EA [98.8 (92.1, 102.8) ms; P<0.05]. There was no significant difference in ADC values between EA and non-EA (P=0.075). The T2 values of G1, G2 and G3 groups in EA were 89.1 (84.4, 94.4) ms, 83.6 (80.9, 86.2) ms, and 76.5 (71.4, 80.3) ms, respectively. There were significant differences in the T2 values between G1 vs G2, G1 vs G3, and G2 vs G3 groups, respectively (all P<0.017). Significant difference was also found in the ADC values between the G1 and G3 groups (P<0.017). The area under the ROC curve (AUC) of T2 values in distinguishing EA from non-EA was 0.867. The AUC of T2 values, ADC values and their combination in predicting high-grade EA was 0.888, 0.730 and 0.895, respectively. The accuracy of synthetic T2WI+ T2 map and conventional T2WI+ DWI in the diagnosis of deep myometrial invasion was 78.1% and 79.5%, respectively, with no significant difference (P>0.05). Conclusions: T2 mapping has great potential in preoperative evaluation of EC. The quantitative T2 value can be used in the diagnosis, pathological classification and grading of EC. The combination of synthetic T2WI and T2 map may be helpful to determine the depth of myometrial invasion.

Clear cell endometrial carcinoma with high microsatellite instability in a complicated pregnancy: a case report

BackgroundEndometrial carcinomas are the most common female genital malignancies. They are very rare in pregnancy and worldwide less than 60 cases associated with pregnancy are published. No clear cell carcinoma has been described in a pregnancy with a live birth.Case presentationWe present the course of a 43-year-old Uyghur female patient with the diagnosis of endometrial carcinoma with a deficiency in the DNA mismatch repair system in the pregnancy. The malignancy with clear cell histology was confirmed by biopsy following the delivery via caesarean section due to preterm birth of a fetus with sonographically suspected tetralogy of Fallot. Earlier whole exome sequencing after amniocentesis had shown a heterozygous mutation in the MSH2 gene, which was unlikely to be related to the fetal cardiac defect. The uterine mass was initially deemed an isthmocervical fibroid by ultrasound and was confirmed as stage II endometrial carcinoma. The patient was consequently treated with surgery, radiotherapy and chemotherapy. Six months after the adjuvant therapy, re-laparotomy was performed due to ileus symptoms and an ileum metastasis was found. The patient is currently undergoing immune checkpoint inhibitor therapy with pembrolizumab.ConclusionRare endometrial carcinoma should be included in the differential diagnosis of uterine masses in pregnant women with risk factors.

Circular RNA differential expression profiles and bioinformatics analysis of hsa_circRNA_079422 in human endometrial carcinoma

The aim of our study was to explore circular RNA (circRNA) expression profiles associated with human endometrial carcinoma (EC) and to analyse the molecular mechanisms involved in cancer development and their potential clinical importance. Differential expression profiles were revealed by Arraystar human circRNA microarray analysis. The results of the circRNA microarray were confirmed by quantitative real-time PCR. Interactions between circRNAs and microRNAs (miRNAs) were predicted using Arraystar’s miRNA target prediction software. The functions of the circRNA-miRNA coexpression network were identified by KEGG pathway analysis and GO analysis. Compared with para-tumorous tissues, 14 genes were significantly upregulated and 12 genes were significantly downregulated in EC tissues (P < 0.05). The quantitative real-time PCR data demonstrated consistency with the results of the microarray profile analysis. We generated a circRNA-miRNA coexpression network. Hsa_circRNA_079422 expression was significantly lower and miR-136-5p expression was higher in EC tissues than in normal endometrial tissues. KEGG pathway analysis and GO analysis indicated that hsa_circRNA_079422 might play roles in different signalling pathways and biological functions. We confirmed the presence of different circRNA expression profiles and predicted the circRNA-miRNA coexpression network in human EC tissues. Hsa_circRNA_079422 might be involved in the pathogenesis and biological process of EC via interactions with miRNAs. IMPACT STATEMENT What is already known on this subject? EC is a common malignancy of the female reproductive system. CircRNAs were demonstrated to exert critical roles in cancers, including EC. What do the results of this study add? The results of this study add circRNAs expression profiles, the circRNA-miRNA coexpression network and cancer-related circRNA-miRNA target genes in EC. It was first found that hsa_circRNA_079422 was downregulated, while miR-136-5p was upregulated in EC tissues. What are the implications of these findings for clinical practice and/or further research? In clinical practice, early EC diagnosis lacks specific biomarkers, so most EC patients are diagnosed at an advanced stage. In the management of EC patients, we also lack personalised adjuvant treatment that combines the clinical pathological characteristics. For the existing literature, we identified a new EC differential expression biomarker, hsa_circ_079422. It can be used to verify the correlation with EC clinical severity or poor prognosis. Its targeting can also be used to stratify EC patients with different molecular types, including to guide adjuvant therapy. In addition, we can verify and analyse regulatory pathways associated with it for the design of regulating engineering circRNA.

Recommandations pour la pratique clinique Nice/Saint-Paul-de-Vence 2022–2023 : Diagnostic histomoléculaire des carcinomes de l'endomètre

French recommendations for clinical practice Nice-Saint-Paul de Vence 2022-2023: histomolecular diagnosis of endometrial carcinomas The characterisation of endometrial carcinomas has been recently modified and enriched by molecular classification, the integration of which now impacts therapeutic decisions on whether adjuvant therapy should be administered or not in localized tumors, and influences treatment selection in advanced disease. Mandatory information includes histological type according to WHO 2020 classification, histological grade, hormone receptors status and molecular classification, the main new elements to provide being analysis of MMR proteins, p53 status and POLE status in selected cases. Sampling and preparation of material must be performed adequately to allow complete analysis. Numerous markers can be used to better define histological type, distinguish between primary lesion or metastases, or provide prognostic information. Determination of MMR/MSI profile is complex but well defined by guidelines that precisely describe techniques to be used and interpretation rules. Knowledge of POLE status is useful to guide therapeutic strategy, especially to consider de-escalation in stages I and II, in particular in case of high grade and/or p53 mutated tumors. This is why indications of POLE determination must be well defined. Finally, oncogenetics consultation is recommended in dMMR tumors (except in case or MLH1 promoter methylation) and in patients with evocative familial history.

Effectiveness of endometrial biopsy and diagnostic dilatation and curettage aiming adequate specimen collection for histopathology for the diagnosis of endometrial carcinoma in patients with abnormal vaginal bleeding.

Objective: To compare the effectiveness of endometrial biopsy and diagnostic dilatation and curettage (D&amp;C) in terms of adequate specimen collection for histopathology for diagnosing endometrial carcinoma in patients with abnormal vaginal bleeding. Study Design: Randomized Controlled Trial. Setting: Department of Obstetrics &amp; Gynecology, Bahawalpur Medical &amp; Dental College, Bahawalpur. Period: October 2022 to March 2023. Material &amp; Methods: A total of 172 peri and post-menopausal women with abnormal uterine bleeding of more than 6 months were analyzed. Randomization was 1:1 for biopsy group (n=86) and D&amp;C group (n=86). Patients in biopsy group underwent biopsy endometrial sampling while those in D&amp;C group underwent diagnostic D&amp;C for endometrial sampling. In biopsy group pipelle suction curette was used to collect the specimen. In D&amp;C group, procedures were done employing general anesthesia. Obtained samples were sent for histopathology examination. Results: In a total of 172 women, the mean duration of abnormal vaginal bleeding were 9.267±2.37 months and 9.174±2.33 months in in biopsy and D&amp;C groups respectively. Adequate specimen collection was noted in 93% women in biopsy group as compare to 97.7% in D&amp;C group (p=0.147). Conclusion: Diagnostic dilatation and curettage as well as endometrial biopsy were effective in terms of adequate specimen collection for histopathology. Endometrial sampling using Pipelle was safe and accurate procedure conducted in outpatient department that avoided general anesthesia.

Hematological and biochemical markers in determining the diagnosis and stage prediction of endometrial cancer.

To establish whether there is a statistically significant difference in hematological and biochemical parameters between the patients with premalignant changes of the uterine mucosa and those with malignant changes. The aim is to establish whether hematological and biochemical parameters may be useful in predicting the stages of endometrial malignancy and in differentiating premalignant and malignant endometrial changes. A retrospective study included 100 patients (70 with endometrial carcinoma diagnosis and 30 with atypical hyperplasia). We compared hematological and biochemical parameters in both groups. CRP, granulocytes, platelets, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) are statistically significantly higher in patients with malignant changes. Lymphocyte count is statistically significantly lower in patients with malignant changes. Platelet count is statistically significantly lower in patients with stages I and II in comparison to patients with higher disease stage. NLR and PLR have good discriminatory power for carcinoma presence. Patients with advanced changes have statistically significantly higher CRP values, higher granulocyte and platelet count, as well as higher values of NLR and PLR, and statistically significantly lower values of lymphocytes and MPV in comparison to benign changes. There is a possibility of using hematological and biochemical parameters in the assessment of endometrial changes as well as in the prediction of stages, in confirmed malignant changes of the endometrium.

P16 expression as a diagnostic parameter of endometrial carcinoma and endometrial hyperplasia

Background: Endometrial cancer is malignant epithelial neoplasm originating from endometrium; endometrial cancer is the sixth most common cancer in women and the fifteenth most common cancer worldwide. The aim of study is to evaluate the expression of P16 IHC in endometrial carcinoma; and its diagnostic role in different histopathological types of endometrial carcinoma. Method: Retrospective study of 70 cases with collection of paraffin embedded tissue blocks and clinical data of patients with endometrial carcinoma and endometrial hyperplasia. H&E staining of slides done to confirm the histopathological diagnosis by specialist pathologist and then stained immunohistochemically for P16 marker. Results: In the current study, the average age of women was 32 to 78 years with a mean age of 53.42. More than half of the women with endometrial carcinoma (EC) (66.6%) presented in the age group between 50 and 70 years, half of the patients with atypical hyperplasia (50%) fall in the same age group as endometrial carcinoma, and the rest of the atypical hyperplasia patients and 65% of those without atypia presented in younger ages (30-50 years’ age group). (63.3%) of patients with endometrial cancer had postmenopausal bleeding; 70% of patients with atypical endometrial hyperplasia and 75% of those without atypia had excessive monthly bleeding (HMB). Histopathology correlated with patient age and clinical presentation. P16 immune marker expression did not correlate with stage at diagnosis of endometrial cancer in TAH & BSO instances. All endometrial serous carcinoma and more than half of EEC had positive p16 IHC. Endometrial hyperplasia had no P16 IHC expression, although more than half of endometrial cancer cases did. Conclusion: All endometrial serous carcinomas expressed high P16 IHC stain. More than half of endometrioid carcinomas had p16 IHC stain, with significant expression in high-grade morphological sections (FIGO 3). Most low-grade endometrioid carcinomas are P16-negative. P16 loss in all endometrial hyperplasia. P16 immunohistochemistry marker aids endometrial carcinoma diagnosis.

Research progress on the relationship between common hematological indicators and endometrial carcinoma

Endometrial carcinoma (EC) is one of the most common malignant tumors in female reproductive tract, which mainly occurs in perimenopausal and postmenopausal women and has a good prognosis. Due to the increase of life expectancy and the change of living habits, the incidence of cervical cancer has been rising continuously in recent years, and patients are getting younger and younger. In some developed cities in China, the incidence of EC has reached the first place in gynecological malignant tumors. From the point of view of secondary prevention, making early screening strategy is the fundamental way to reduce the incidence of EC. Studies show that the hematological indexes of normal endometrial patients and EC patients are different, which is of great significance for early diagnosis, treatment and improvement of prognosis of EC patients. In order to provide reference for the early diagnosis and treatment of EC, this paper reviews the research status of hematological indexes in the diagnosis and treatment of EC.