Invasion In Endometrial Carcinoma Research Articles

Mechanism of E2F1 in the proliferation, migration, and invasion of endometrial carcinoma cells via the regulation of BMI1 transcription.

Endometrial carcinoma (EC) is the most prevalent gynecological cancer. Transcription factor (TF) regulates a large number of downstream target genes and is a key determinant of all physiological activities, including cell proliferation, differentiation, apoptosis, and cell cycle. The transcription factor E2F1 shows prominent roles in EC. BMI1 is a member of Polycomb suppressor Complex 1 (PRC1) and has been shown to be associated with EC invasiveness. It is currently unclear whether E2F1 can participate in the proliferation, migration, and invasion processes of EC cells by regulating BMI1 transcription. We investigated whether E2F1 could participate in the proliferation, migration, and invasion processes of EC cells by regulating BMI1 transcription, in order to further clarify the pathogenesis and etiology of EC, and provide reference for identifying potential therapeutic targets and developing effective prevention and treatment strategies for this disease. Human endometrial epithelial cells (hEECs) and human EC cell lines were selected. E2F1 expression was assessed by Western blot. E2F1 was silenced in AN3CA or overexpressed in HEC-1 by transfections, or E2F1 was silenced and BMI1 was overexpressed in AN3CA by cotransfection. Cell proliferation, migration, and invasion were detected by MTT, wound healing, and Transwell assays. The binding sites between E2F1 and BMI1 promoters were predicted through JASPAR website, and the targeted binding was verified by dual-luciferase report and ChIP assays. E2F1 was up-regulated in human EC cell lines, with its expression highest in AN3CA, and lowest in HEC-1. AN3CA invasion, migration, and proliferation were repressed by E2F1 knockdown, while those of HEC-1 cells were promoted by E2F1 overexpression. E2F1 overexpression increased the activity of wild type BMI1 reporter vector promoter, while this promotion was weakened after mutation of the predicted binding site in the BMI1 promoter. In the precipitated E2F1, BMI1 promoter site level was higher than that of IgG immunoprecipitant. BMI1 silencing suppressed AN3CA cell growth. BMI1 overexpression partially abrogated E2F1 silencing-inhibited EC cell growth. E2F1 promoted EC cell proliferation, invasion, and migration by promoting the transcription of BMI1.

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.

Diagnostic accuracy of MRI for assessing lymphovascular space invasion in endometrial carcinoma: a meta-analysis.

The lymphovascular space invasion (LVSI) status of endometrial cancer (EC) has guiding significance in lymph node dissection. However, LVSI can only be obtained after surgery. Researchers have tried to extract the information of LVSI using magnetic resonance imaging (MRI). To evaluate the ability of preoperative MRI to predict the LVSI status of EC. A search was conducted by using the PubMed/MEDLINE, EMBASE, Web of Science, and the Cochrane Library databases. Articles were included according to the criteria. Methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2. A bivariate random effects model was used to obtain pooled summary estimates, heterogeneity, and the area under the summary receiver operating characteristic curve (AUC). A subgroup analysis was performed to identify sources of heterogeneity. A total of nine articles (814 patients) were included. The risk of bias was low or unclear for most studies, and the applicability concerns were low or unclear for all studies. The summary AUC values as well as pooled sensitivity and specificity of LVSI status in EC were 0.82, 73%, and 77%, respectively. According to the subgroup analysis, radiomics/non-radiomics features, country/region, sample size, age, MR manufacturer, magnetic field, scores of risk bias, and scores of applicability concern may have caused heterogeneity. Our meta-analysis showed that MRI has moderate diagnostic efficacy for LVSI status in EC. Large-sample, uniformly designed studies are needed to verify the true value of MRI in assessing LVSI.

Landscape of chromatin remodeling gene alterations in endometrial carcinoma

ObjectiveChromatin remodeling genes (CRGs) encode components of epigenetic regulatory mechanisms and alterations in these genes have been identified in several tumor types, including gynecologic cancers. In this study, we sought to investigate the prevalence and clinicopathological associations of CRG alterations in endometrial carcinoma (EC). MethodsWe performed a retrospective analysis of 660 ECs sequenced using a clinical massively parallel sequencing assay targeting up to 468 genes, including 25 CRGs, and defined the presence of somatic CRG alterations. Clinicopathologic features were obtained for all cases. Immunohistochemical interrogation of ARID1A and PTEN proteins was performed in a subset of samples. ResultsOf the 660 ECs sequenced, 438 (66.4%) harbored CRG alterations covered by our panel. The most commonly altered CRG was ARID1A (46%), followed by CTCF (21%), KMT2D (18%), KMT2B (17%), BCOR (16%), ARID1B (12%) and SMARCA4 (11%). We found that ARID1A genetic alterations were preferentially bi-allelic and often corresponded to altered ARID1A protein expression in ECs. We further observed that ARID1A alterations were often subclonal when compared to PTEN alterations, which were primarily clonal in ECs harboring both mutations. Finally, CRG alterations were associated with an increased likelihood of myometrial and lymphovascular invasion in endometrioid ECs. ConclusionCRG alterations are common in EC and are associated with clinicopathologic features and likely play a crucial role in EC.

Association of Lymphovascular Space Invasion (LVSI) with Histological Tumor Grade and Myometrial Invasion in Endometrial Carcinoma: A Review Study.

Endometrial carcinoma is one of the most frequent gynecological cancers in developed countries. Lymphovascular space invasion (LVSI), histological grade, and myometrial invasion (MMI) are important prognostic factors of endometrial carcinoma. LVSI is considered an independent poor prognostic factor in endometrial carcinoma. Based on the importance of LVSI, this study aimed to discuss the association of LVSI with tumor grade and MMI. A search of PubMed, EMBASE, Web of Science, Scopus, Google Scholar, and Cochrane Library was carried out to collect related studies. Consequently, most studies showed that LVSI is significantly associated with higher histologic grade and deep MMI.

S100A7 promotes endometrial carcinoma progression by activating the MAPK signaling pathway

S100 calcium binding protein A7 (S100A7) has been proofed to play a carcinogenic role in several cancers. However, its role and the regulatory mechanism in Endometrial carcinoma (EC) was unknown. Western blot was applied to determine the expression of S100A7 and Mitogen-activated protein kinase (MAPK) pathway-related protein in EC cells. Functional in vitro experiments were conducted to explore the effects of S100A7 on cell proliferation, apoptosis, migration, invasion and angiogenesis in EC. As a result, S100A7 expression was dramatically up-regulated in EC cells. Overexpression of S100A7 enhanced EC cells proliferation, migration, invasion and angiogenesis, and suppressed cell apoptosis, as well as activated MAPK signaling pathway. Whereas, knockdown of S100A7 exerted the opposite effects. Our finding suggested that S100A7 may promote the malignant progression of EC by activating MAPK pathway, implying S100A7 has significant potential to be used as an emerging therapeutic target for EC treatment.

XPO1-Mediated EIF1AX Cytoplasmic Relocation Promotes Tumor Migration and Invasion in Endometrial Carcinoma.

Dysregulation of eukaryotic translation initiation factor 1A, X-linked (EIF1AX), has been implicated in the pathogenesis of some cancers. However, the role of EIF1AX in endometrial carcinoma (EC) remains unknown. We investigated the EIF1AX expression in EC patients and assessed its tumorigenesis-associated function and nucleocytoplasmic transport mechanism in vitro and in vivo. The results indicated that the cytoplasmic EIF1AX expression showed a gradual increase when going from endometrium normal tissue, simple endometrial hyperplasia, complex endometrial hyperplasia, and endometrial atypical hyperplasia to EC, while vice versa for the nuclear EIF1AX expression. In addition, the cytoplasmic EIF1AX expression was positively correlated with histologic type, high International Federation of Gynecology and Obstetrics (FIGO) grade, advanced FIGO stage, deeper infiltration, high Ki67 index, and shorter recurrence-free survival in EC patients. In vitro, short hairpin RNA-mediated EIF1AX depletion or SV40NLS-mediated EIF1AX import into the nucleus in multiple human EC cells potently suppressed cell migration and invasion, epithelial-mesenchymal transition, and lung metastasis. Moreover, exportin 1 induced the transport of EIF1AX from the nucleus to the cytoplasm that could be inhibited by leptomycin B treatment or the mutation in the EIF1AX location sequence. These results demonstrate that cytoplasmic EIF1AX may play a key role in the incidence and promotion of EC, and thus, targeting EIF1AX or its nucleocytoplasmic transport process may offer an effective new therapeutic approach to EC.

A review of Molecular Mechanism of Endometrial Carcinoma Invasion and Tumor Markers

A review of Molecular Mechanism of Endometrial Carcinoma Invasion and Tumor Markers

The roles and clinical applications of interleukins in endometrial carcinoma.

As a common malignant tumor of the female reproductive system, endometrial carcinoma (EC) seriously endangers women's health with an increasing incidence. The oncogenesis and progression of cancer are closely linked with immune microenvironment, of which interleukins are the important components. In order to illustrate the roles and clinical applications of interleukins in EC, literature of interleukins and EC were reviewed. Based on the present studies, interleukins play crucial roles in the oncogenesis and development of EC via regulating the proliferation, migration, invasion, angiogenesis, apoptosis, pyroptosis and autophagy of EC as well as the immune function against EC. And some of the interleukins seems to have prospective clinical applications in EC, such as evaluating the risk of tumorigenesis, discriminating the malignancy from benign disorders or normal condition, indicating cancer aggressiveness, predicting the prognosis of patients and serving as the novel therapy. However, there is still a long way to go before the clinical applications of interleukins in EC come into reality. Nevertheless, it is certain that the exploration of interleukins will definitely be of great benefit to the screening, diagnosis and treatment of EC in the future.

Tissue Characteristics of Endometrial Carcinoma Analyzed by Quantitative Synthetic MRI and Diffusion-Weighted Imaging.

This study investigates the association of T1, T2, proton density (PD) and the apparent diffusion coefficient (ADC) with histopathologic features of endometrial carcinoma (EC). One hundred and nine EC patients were prospectively enrolled from August 2019 to December 2020. Synthetic magnetic resonance imaging (MRI) was acquired through one acquisition, in addition to diffusion-weighted imaging (DWI) and other conventional sequences using 1.5T MRI. T1, T2, PD derived from synthetic MRI and ADC derived from DWI were compared among different histopathologic features, namely the depth of myometrial invasion (MI), tumor grade, cervical stromal invasion (CSI) and lymphovascular invasion (LVSI) of EC by the Mann-Whitney U test. Classification models based on the significant MRI metrics were constructed with their respective receiver operating characteristic (ROC) curves, and their micro-averaged ROC was used to evaluate the overall performance of these significant MRI metrics in determining aggressive histopathologic features of EC. EC with MI had significantly lower T2, PD and ADC than those without MI (p = 0.007, 0.006 and 0.043, respectively). Grade 2-3 EC and EC with LVSI had significantly lower ADC than grade 1 EC and EC without LVSI, respectively (p = 0.005, p = 0.020). There were no differences in the MRI metrics in EC with or without CSI. Micro-averaged ROC of the three models had an area under the curve of 0.83. Synthetic MRI provided quantitative metrics to characterize EC with one single acquisition. Low T2, PD and ADC were associated with aggressive histopathologic features of EC, offering excellent performance in determining aggressive histopathologic features of EC.

Preoperative Evaluation of 3D-MRI on the Depth of Myometrial Invasion of Endometrial Carcinoma: 3D Study of Endometrial Carcinoma

Background: To evaluate the preoperative diagnostic efficacy of 3D-MRI for the depth of myometrial invasion of endometrial carcinoma. Methods: A total of 116 patients with endometrial carcinoma who had undergone pelvic MRI before surgery were included. Mimics 21.0 (Materialize Co., Belgium) software was used to reconstruct three-dimensional MRI models (3D-MRI). The tumor volume and surface area, uterine volume and surface area were measured, and the tumor volume ratio was calculated. TVR (Tumor Volume Ratio) = tumor volume/uterine volume, TAR (Tumor Area Ratio) = tumor surface area/uterine surface area. Postoperative pathology was used as the gold standard to compare the accuracy, sensitivity, specificity, negative predictive value, and positive predictive value of conventional MRI and 3D-MRI in preoperative assessment of endometrial carcinoma myometrial invasion. Results: The accuracy and specificity of 3D-MRI in the diagnosis of deep myometrial invasion were better than conventional MRI (p &lt; 0.05). There was no statistically significant difference in tumor volume or surface area between stage IA and stage IB (p &gt; 0.05), while TVR and TAR showed significant statistical differences (8.05 ± 0.66 vs. 19.12 ± 3.20, p &lt; 0.01; 21.38 ± 1.04 vs. 35.15 ± 3.42, p &lt; 0.01). Further analysis, the area under the ROC curve of TVR is 0.738, p &lt; 0.01, and the best cut-off value is 13.59%; the area under the ROC curve of TAR is 0.770, p &lt; 0.01, and the best cut-off value is 27.41%. Conclusions: Preoperative 3D-MRI can effectively assess the myometrial invasion of endometrial carcinoma.

A Comparison of Dynamic Contrast-Enhanced Magnetic Resonance Imaging and T2-Weighted Imaging in Determining the Depth of Myometrial Invasion in Endometrial Carcinoma-A Retrospective Study.

This study aims to compare dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with T2-weighted imaging (T2WI) in defining the depth of myometrial invasion in endometrial carcinoma. This retrospective study included 32 subjects with endometrial carcinoma who underwent 3.0T magnetic resonance imaging (MRI) prior to hysterectomy. DCE-MRI and T2WI were evaluated to determine the depth of myometrial invasion in endometrial carcinoma. A set of data consisting of the sensitivity, specificity, predictive values, and accuracy of DCE-MRI and T2WI were obtained and compared with the histopathological results. Out of the 32 cases included, the histopathological examination revealed that 50% myometrial invasion was found in 11 patients and ≥50% myometrial invasion was found in 21 patients. In the assessment of the tumor invasion, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of T2WI were 45.45%, 90.48 %, 71.43%, 76.0%, and 75.0%, respectively. The corresponding values for DCE-MRI were 81.82%, 76.19%, 64.29%, 88.89 %, and 78.12%, respectively. When T2WI were read together with DCE-MRI, the values were 90.91%, 90.48%, 83.33%, 95.0%, and 90.62%, respectively. Thus, the sensitivity and accuracy of DCE-MRI were greater compared to T2WI in defining the depth of myometrial invasion. However, the merging of T2WI and DCE-MRI increased the specificity and PPV value and improved the sensitivity, NPV and accuracy in detecting myometrial invasion. DCE-MRI was more sensitive but less specific than T2WI in defining the depth of myometrial invasion. In conclusion, combining DCE-MRI and T2WI further improves the diagnostic performance for myometrial invasion in endometrial carcinoma.

LncRNA GATA3-AS1 promoted invasion and migration in human endometrial carcinoma by regulating the miR-361/ARRB2 axis

Endometrial carcinoma (EC) is a kind of fatal female malignancy. lncRNA GATA3-AS1 has been identified as an oncogene in various cancers. However, the functions and mechanisms of GATA3-AS1 in EC remain to be explored. Human EC tissues and four EC cell lines were used. Western blotting and quantitative real-time PCR (qRT-PCR) were used to evaluate the expression of GATA3-AS1, miR-361, and ARRB2. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction among GATA3-AS1, miR-361, and ARRB2. Flow cytometry, colony formation assay, scratch assay, and transwell assay were used to examine the cell apoptosis, proliferation, migration, and invasion of EC cells, respectively. In vivo tumor growth was monitored in nude mice. GATA3-AS1 and ARRB2 were upregulated while miR-361 was downregulated in human EC tissues and EC cells. GATA3-AS1 knockdown constrained cell proliferation, invasion, migration, and EMT while promoting the apoptosis of EC cells by upregulating miR-361. GATA3-AS1 negatively regulated miR-361 expression. ARRB2 was the direct target of miR-361 and could activate the Src/Akt pathway. In vivo, GATA3-AS1 knockdown suppressed tumor progression by upregulating the miR-361 expression. lncRNA GATA3-AS1 promoted EC invasion and migration by the miR-361/ARRB2 axis, which indicated that GATA3-AS1 might be a promising therapeutic option for advanced EC progression. KEY MESSAGES: GATA3-AS1 knockdown suppressed EC proliferation, invasion, and migration. GATA3-AS1 directly inhibited miR-361 as a ceRNA. MiR-361 knockdown reversed the tumor suppressive effect caused by GATA3-AS1 knockdown. MiR-361 bound to ARRB2 directly and suppressed its expression. The GATA3-AS1/miR-361/ARRB2 axis regulated EC cell proliferation, invasion, and migration.

Evaluation of the Depth of Myometrial Invasion of Endometrial Carcinoma: Comparison of Orthogonal Pelvis-axial Contrast-enhanced and Uterus-axial Dynamic Contrast-enhanced MRI Protocols

To compare the diagnostic performance of orthogonal pelvis-axial (OPA) contrast-enhanced (CE) and orthogonal uterus-axial (OUA) dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) protocols in assessing the depth of myometrial invasion (MI) of endometrial carcinoma (EC). Preoperative MRI of 398 consecutive EC patients (197 patients with OPA CE-MRI protocol and 201 patients with OUA DCE-MRI protocol) was analyzed. Two radiologists independently interpreted the depth of MI, with postoperative histopathology as the reference standard. The chi-square test, Fisher's exact test, and receiver operating characteristic curve analysis were used for diagnostic performance comparison. OUA DCE-MRI showed a significantly larger area under the curve than OPA CE-MRI in detecting the presence of MI for radiologist 1 (0.71 versus 0.49, p < 0.05) but not for radiologist 2 or deep MI (all p > 0.05). Compared to OPA CE-MRI, OUA DCE-MRI significantly improved the diagnostic accuracy of non-MI and superficial MI (radiologist 1: 45.5% versus 0 and 88.7% versus 86.4%, p=0.045 and 0.567, respectively; radiologist 2: 45.5% versus 12.5% and 88.7% versus 78.8%, p=0.177 and 0.027, respectively) and of EC with adenomyosis/submucous myomas, cornual tumor, and antero-posterior diameter ≤ 10 mm (radiologist 1: 86.4% versus 71.4%, 91.2% versus 67.7%, and 90.1% versus 81.1%, p=0.048, 0.018, and 0.081, respectively; radiologist 2: 86.4% versus 64.3%, 88.2% versus 64.5%, and 87.0% versus 71.6%, p=0.006, 0.023, and 0.019, respectively). The OUA DCE-MRI protocol was superior to the OPA CE-MRI protocol in assessing the depth of MI of EC.

Tumor stiffness measured by 3D magnetic resonance elastography can help predict the aggressiveness of endometrial carcinoma: preliminary findings

BackgroundPreoperative evaluation of aggressiveness, including tumor histological subtype, grade of differentiation, Federation International of Gynecology and Obstetrics (FIGO) stage, and depth of myometrial invasion, is significant for treatment planning and prognosis in endometrial carcinoma (EC). The purpose of this study was to evaluate whether three-dimensional (3D) magnetic resonance elastography (MRE) can help predict the aggressiveness of EC.MethodsFrom August 2015 to January 2019, 82 consecutive patients with suspected uterine tumors underwent pelvic MRI and MRE scans, and 15 patients with confirmed EC after surgical resection were enrolled. According to pathological results (tumor grade, histological subtype, FIGO stage, and myometrial invasiveness), the patients were divided into two subgroups. The independent-samples t-test or Mann-Whitney U test was used to compare the stiffness between different groups. The diagnostic performance was determined with receiver operating characteristic (ROC) curve analysis.ResultsThe stiffness of EC with ≥ 50 % (n = 6) myometrial invasion was significantly higher than that with < 50 % (n = 9) myometrial invasion (3.68 ± 0.59 kPa vs. 2.61 ± 0.72 kPa, p = 0.009). Using a stiffness of 3.04 kPa as a cutoff value resulted in 100 % sensitivity and 77.8 % specificity for differentiating ≥ 50 % myometrial invasion from < 50 % myometrial invasion of EC. The stiffness of poorly differentiated EC (n = 8) was significantly higher than that of well/moderately differentiated EC (n = 7) (3.47 ± 0.64 kPa vs. 2.55 ± 0.82 kPa, p = 0.028). Using a stiffness of 3.04 kPa as a cutoff value resulted in 75 % sensitivity and 71.4 % specificity for differentiating poorly differentiated from well/moderately differentiated EC. The stiffness of FIGO stage II/III EC was significantly higher than that of FIGO stage I EC (3.69 ± 0.65 kPa vs. 2.72 ± 0.76 kPa, p = 0.030). Using a stiffness of 3.04 kPa as a cutoff value resulted in 100 % sensitivity and 70 % specificity for differentiating FIGO stage I EC from FIGO stage II/III EC. The tumor stiffness value in type II (n = 3) EC was higher than that in type I (n = 12) EC (3.67 ± 0.59 kPa vs. 2.88 ± 0.85 kPa), but the difference was not significant (p = 0.136).ConclusionsTumor stiffness measured by 3D MRE may be potentially useful for predicting tumor grade, FIGO stage and myometrial invasion of EC and can aid in the preoperative risk stratification of EC.

Characterization of the Endometrial MSC Marker Ectonucleoside Triphosphate Diphosphohydrolase-2 (NTPDase2/CD39L1) in Low- and High-Grade Endometrial Carcinomas: Loss of Stromal Expression in the Invasive Phenotypes.

Ectonucleoside triphosphate diphosphohydrolase-2 (NTPDase2/CD39L1) has been described in human non-pathological endometrium in both epithelial and stromal components without changes along the cycle. It was identified as a stromal marker of basalis. In the present study, we aimed to evaluate NTPDase2 distribution, using immunolabeling and in situ enzyme activity approaches, in endometrial carcinoma (EC) at different tumor grades. NTPDase2 was present in tumor epithelial EC cells, as in the non-pathological endometria, but the expression underwent changes in subcellular distribution and also tended to decrease with the tumor grade. In stroma, NTPDase2 was identified exclusively at the tumor-myometrial junction but this expression was lost in tumors of invasive phenotype. We have also identified in EC samples the presence of the perivascular population of endometrial mesenchymal stem cells (eMSCs) positive for sushi domain containing 2 (SUSD2) and for NTPDase2, already described in non-tumoral endometrium. Our results point to NTPDase2 as a histopathological marker of tumor invasion in EC, with diagnostic relevance especially in cases of EC coexisting with other endometrial disorders, such as adenomyosis, which occasionally hampers the assessment of tumor invasion parameters.

MRI-based traditional radiomics and computer-vision nomogram for predicting lymphovascular space invasion in endometrial carcinoma

PurposeTo determine the capabilities of MRI-based traditional radiomics and computer-vision (CV) nomogram for predicting lymphovascular space invasion (LVSI) in patients with endometrial carcinoma (EC). Materials and methodsA total of 184 women (mean age, 52.9±9.0 [SD] years; range, 28–82 years) with EC were retrospectively included. Traditional radiomics features and CV features were extracted from preoperative T2-weighted and dynamic contrast-enhanced MR images. Two models (Model 1, the radiomics model; Model 2, adding CV radiomics signature into the Model 1) were built. The performance of the models was evaluated by the area under the curve (AUC) of the receiver operator characteristic (ROC) in the training and test cohorts. A nomogram based on clinicopathological metrics and radiomics signatures was developed. The predictive performance of the nomogram was assessed by AUC of the ROC in the training and test cohorts. ResultsFor predicting LVSI, the AUC values of Model 1 in the training and test cohorts were 0.79 (95% confidence interval [CI]: 0.702–0.889; accuracy: 65.9%; sensitivity: 88.8%; specificity: 57.8%) and 0.75 (95% CI: 0.585–0.914; accuracy: 69.5%; sensitivity: 85.7%; specificity: 62.5%), respectively. The AUC values of Model 2 in the training and test cohorts were 0.93 (95% CI: 0.875–0.991; accuracy: 94.9%; sensitivity: 91.6%; specificity: 96.0%) and 0.81 (95% CI: 0.666–0.962; accuracy: 71.7%; sensitivity: 92.8%; specificity: 62.5%), respectively. The discriminative ability of Model 2 was significantly improved compared to Model 1 (Net Reclassification Improvement [NRI]=0.21; P=0.04). Based on histologic grade, FIGO stage, Rad-score and CV-score, AUC values of the nomogram to predict LVSI in the training and test cohorts were 0.98 (95% CI: 0.955–1; accuracy: 91.6%; sensitivity: 91.6%; specificity: 96.0%) and 0.92 (95% CI: 0.823–1; accuracy: 91.3%; sensitivity: 78.5%; specificity: 96.8%), respectively. ConclusionsMRI-based traditional radiomics and computer-vision nomogram are useful for preoperative risk stratification in patients with EC and may facilitate better clinical decision-making.

Lymphovascular space invasion in endometrial carcinoma: Tumor size and location matter

ObjectiveTo analyze histological factors possibly associated with lymphovascular space invasion (LVSI) and to determine which of those can act as independent surrogate markers. MethodsRetrospective cohort study performed between January 2001 and December 2014. LVSI was defined as the presence of tumor cells inside a space completely surrounded by endothelial cells. Risk factors evaluated included myometrial invasion, tumor grade, size, location, and cervical invasion. Univariate logistical regression models were applied to study any possible association of LVSI with these factors. Values were adjusted by multivariate logistic regression analysis. ResultsA total of 327 patients with endometrial carcinoma treated in our Centre were included. LVSI was observed in 120 patients (36.7%). Lower uterine segment involvement (OR 5.21, 95% CI:2.6–10.4, p < 0.001) and size ≥2 cm (OR 2.62, 95% CI: 1.14–6.1, p < 0.001) were independent factors for LSVI in multivariate analysis. In univariate analysis, LVSI was a surrogate marker in type 1 tumors with deep myometrial invasion (IB, 51.9% vs. IA, 16.0%; p < 0.001), grade 3 (G3 55.8% vs. G1 16.2%; p < 0.001), size ≥2 cm (37.9% vs. 16.1%, p = 0.005), those with involving the lower segment of the uterus (58.9% vs. 22.5%, p < 0.001) and/or with cervical stromal invasion (65.4% vs. 26.1%, p < 0.001), and in type 2 tumors (61.5% vs. 30.5%, p < 0.001). The use of uterine manipulator did not increase the rate of LVSI (35.5% vs. 40.5%, p = 0.612) as compared to no manipulator use. ConclusionsSize ≥2 cm and involvement of the lower uterine segment are independent factors for LSVI, in type 1 tumors, which can be used for surgical planning. LVSI is also more common in type 1 tumors with deep myometrial invasion, grade 3 and/or cervical stromal invasion, and also in type 2 tumors. The use of a uterine manipulator does not increase LVSI.

Assessment of myometrial invasion of endometrial carcinoma with preoperative transvaginal sonography

Objective: Routine pelvic and para-aortic lymphadenectomy up to the level of the renal veins is controversial in endometrial cancer as the complication rate and prolonging the operation time is considerable. Intraoperative frozen section analysis of the uterus is the mainstay for the decision of performing a staging lymphadenectomy. Preoperative estimation of myometrial invasion may be useful for surgical planning. Our objective is to assess the accuracy of preoperative transvaginal ultrasound for identifying myometrial invasion. Methods: 80 consecutive patients operated between August 2017 and December 2019 with a histologically confirmed diagnosis of endometrial carcinoma evaluated within two weeks before surgery by transvaginal ultrasound are the subject of this study. Myometrial invasion estimation is documented and intraoperative frozen section analysis and final pathologic diagnosis as the reference standard was recorded. Results: Preoperative TVUS had 76.5% sensitivity, 91.3% specificity, whereas frozen section analysis had 85.3% sensitivity and 93.5% specificity, and they correlate well with each other (P &lt; 0.01). Agreement between these two methods was substantial according to Cohen’s kappa index (κ) = 0.74 (P &lt; 0.01) and percentage of agreement was 88%. Increasing tumor diameter decreased the prediction accuracy of preoperative ultrasound (P &lt; 0.01). Conclusion: There is good correlation of preoperative transvaginal ultrasound with intraoperative frozen section analysis and final pathology results. The subjective assessment of transvaginal ultrasound can guide surgeons as a useful preoperative tool for preparing surgery

Long Non-Coding RNA SNHG14 Impedes Viability, Migration and Invasion of Endometrial Carcinoma Cells Through Modulating miR-93-5p/ZBTB7A Axis.

BackgroundThe function of long non-coding RNA small nucleolar RNA host gene 14 (SNHG14) in endometrial carcinoma (EC) has not been thoroughly reported. This research is designed to research the action mechanism of SNHG14 in EC development.MethodsThe expression of SNHG14 was estimated in The Cancer Genome Atlas and was verified by qRT-PCR in EC tissues. The correlation between SNHG14 expression and clinicopathological features of EC patients was analyzed. Cell viability, wound healing rate, and relative invasion rate were examined by MTT, wound healing, and transwell assay. StarBase, TargetScan, RNA pull-down, and dual luciferase reporter gene (DLR) assay were conducted to analyze the relationship among SNHG14, miR-93-5p and ZBTB7A.ResultsSNHG14 was underexpressed in EC. SNHG14 expression was significantly relevant to menstruation, FIGO stage, histological grade and lymphatic metastasis of EC patients. SNHG14 overexpression hampered viability, migration and invasion of EC cells. SNHG14 functioned as a sponge for miR-93-5p, and miR-93-5p inhibition restrained cell viability, migration and invasion in EC. In addition, miR-93-5p directly targeted to ZBTB7A, which was underexpressed in EC. The suppressive action of SNHG14 overexpression on the viability, migration and invasion of EC cells was partly rescued by miR-93-5p overexpression or ZBTB7A silencing.ConclusionLncRNA SNHG14 hampered the viability, migration and invasion of EC cells via modulating miR-93-5p/ZBTB7A axis.