Invasion In Endometrial Cancer Research Articles

Multiparametric magnetic resonance imaging-based assessment of the effect of adenomyosis on determining the depth of myometrial invasion in endometrial cancer.

Accurate preoperative diagnosis of endometrial cancer (EC) with deep myometrial invasion (DMI) is critical to deciding whether to perform lymphadenectomy. However, the presence of adenomyosis makes distinguishing DMI from superficial myometrial invasion (SMI) on magnetic resonance imaging (MRI) challenging. We aimed to evaluate the accuracy of multiparametric MRI (mpMRI) in diagnosing DMI in EC coexisting with adenomyosis (EC-A) compared with EC without coexisting adenomyosis and to evaluate the effect of different adenomyosis subtypes on myometrial invasion (MI) depth in EC. Patients with histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage I EC who underwent preoperative MRI were consecutively included in this 2-center retrospective study. Institution 1 was searched from January 2017 to November 2022 and institution 2 was searched from June 2017 to March 2021. Patients were divided into 2 groups: group A, patients with EC-A; group B, EC patients without coexisting adenomyosis, matched 1:2 according to age ±5 years and tumor grade. A senior radiologist assessed the MRI adenomyosis classification in group A. Then, 2 radiologists (R1/R2) independently interpreted T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), T1-weighted contrast-enhanced (T1CE), and a combination of all images (mpMRI) respectively, and then assessed MI depth. Accuracy, sensitivity, specificity, and the areas under the receiver operating curve (AUC) were calculated. The chi-square test was used to compare the accuracy of diagnosing DMI. Interobserver agreement was evaluated using the Kappa test. A total of 70 cases in group A and 140 cases in group B were included. The accuracy, sensitivity, and specificity of consensus were 94.3% [95% confidence interval (CI): 88.9-99.7%] vs. 92.1% (95% CI: 87.7-96.6%), 60.0% (95% CI: 17-92.7%) vs. 86.7% (95% CI: 68.4-95.6%), and 96.9% (95% CI: 88.4-95.5%) vs. 93.6% (95% CI: 86.8-97.2%) (group A vs. group B, respectively). There was no significant difference in the diagnostic accuracy of DMI on each sequence between the groups (Reviewer 1/Reviewer 2): PT2WI=0.14/0.17, PDWI=0.50/0.33, PT1CE=0.90/0.18, PmpMRI=0.50/0.37. The AUC for T2WI, DWI, T1CE, and mpMRI (Reviewer 1/Reviewer 2), respectively, were 0.54 (95% CI: 0.42-0.66)/0.78 (95% CI: 0.67-0.87), 0.63 (95% CI: 0.50-0.74)/0.77 (95% CI: 0.65-0.86), 0.69 (95% CI: 0.57-0.80)/0.79 (95% CI: 0.68-0.88), and 0.91 (95% CI: 0.82-0.97)/0.89 (95% CI: 0.79-0.95) (group A) and 0.83 (95% CI: 0.76-0.89)/0.85 (95% CI: 0.78-0.90), 0.83 (95% CI: 0.76-0.89)/0.86 (95% CI: 0.79-0.91), 0.88 (95% CI: 0.82-0.93)/0.86 (95% CI: 0.80-0.92), and 0.91 (95% CI: 0.85-0.95)/0.87 (95% CI: 0.80-0.92) (group B). Interobserver agreement was highest with mpMRI [κ=0.387/0.695 (case/control)]. The consensus results of MRI categorization of adenomyosis revealed no significant difference in the accuracy of diagnosing DMI by adenomyosis subtype (Pspatial relationship>0.99, Paffected area=0.52, Paffected pattern=0.58, Paffected size>0.99). The presence of adenomyosis or adenomyosis subtype had no significant effect on the interpretation of the depth of MI. T1CE can increase the contrast between adenomyosis and cancer foci; therefore, the information provided by T1CE should be valued.

Can MRI Accurately Diagnose and Stage Endometrial Adenocarcinoma?

Background and Objectives: Endometrial carcinoma is one of the most common gynecological cancers, and benign lesions such as endometrial hyperplasia, polyps, adenomyosis and leiomyomas should be included in the differential diagnosis. Magnetic resonance imaging has an important role in evaluating endometrial cancer and assessing the depth of myometrial invasion, and it closely correlates with the prognosis of the patient. The purpose of this study is to evaluate the MRI semiology of the endometrial carcinomas that mimic benign lesions, the main factors that may affect the correct diagnosis and the feasibility of magnetic resonance imaging to evaluate the depth of the myometrial invasion of endometrial cancer. Materials and Methods: This is a retrospective analysis of 45 patients that underwent MRI examinations and the lesions were pathologically diagnosed as endometrial carcinoma after surgical resection. This study evaluated the staging accuracy of T2-weighted imaging, diffusion-weighted imaging (DWI), ADC mapping and T1-weighted imaging with fat saturation before and after gadolinium injection. Results: In 36 of the 45 cases, the MRI of the lesion showed the characteristics of endometrial cancer and the diagnosis was certain. Nine lesions (20%) were described as unequivocal and had unspecific MR appearance. In eight of the nine cases (89%), the histopathologic report revealed the presence of leiomyomas and two of these cases (22%) were also associated with adenomyosis. The cause of underestimation in these patients was coexisting lesions exhibiting heterogenous intensity and contrast enhancement, which made it difficult to detect the margins of the lesions. The depth of the myometrial invasion was underestimated in nine cases and overestimated in three cases. The staging accuracy with MRI was 74%. There was a significant correlation between MR imaging and histopathologic finding in the assessment of myometrial invasion (p < 0.001). Cervical extension was noted in eight cases (18%), but was missed on MR imaging in two patients and overstaged in none. Six of them were associated with myometrial invasion in more than 50% of the thickness. There was a significant correlation between MR imaging and histopathologic finding in the assessment of cervical extension (p < 0.001). Conclusions: Our data confirm the high accuracy of MRI in the diagnosis and local staging of endometrial carcinoma. The information provided by MRI has an important role in planning the treatment and the prognosis of the patients.

Molecular and pathologic data to guide selection of patients with endometrioid endometrial cancer for ovarian preservation

ObjectivesTo investigate the association of molecular and pathologic factors with concurrent or recurrent ovarian disease to guide ovarian preservation in endometrioid endometrial cancer.MethodsPatients with endometrial cancer ≤50 years of age...

Fully Automated Identification of Lymph Node Metastases and Lymphovascular Invasion in Endometrial Cancer From Multi-Parametric MRI by Deep Learning.

Early and accurate identification of lymphatic node metastasis (LNM) and lymphatic vascular space invasion (LVSI) for endometrial cancer (EC) patients is important for treatment design, but difficult on multi-parametric MRI (mpMRI) images. To develop a deep learning (DL) model to simultaneously identify of LNM and LVSI of EC from mpMRI images. Retrospective. Six hundred twenty-one patients with histologically proven EC from two institutions, including 111 LNM-positive and 168 LVSI-positive, divided into training, internal, and external test cohorts of 398, 169, and 54 patients, respectively. T2-weighted imaging (T2WI), contrast-enhanced T1WI (CE-T1WI), and diffusion-weighted imaging (DWI) were scanned with turbo spin-echo, gradient-echo, and two-dimensional echo-planar sequences, using either a 1.5 T or 3 T system. EC lesions were manually delineated on T2WI by two radiologists and used to train an nnU-Net model for automatic segmentation. A multi-task DL model was developed to simultaneously identify LNM and LVSI positive status using the segmented EC lesion regions and T2WI, CE-T1WI, and DWI images as inputs. The performance of the model for LNM-positive diagnosis was compared with those of three radiologists in the external test cohort. Dice similarity coefficient (DSC) was used to evaluate segmentation results. Receiver Operating Characteristic (ROC) analysis was used to assess the performance of LNM and LVSI status identification. P value <0.05 was considered significant. EC lesion segmentation model achieved mean DSC values of 0.700 ± 0.25 and 0.693 ± 0.21 in the internal and external test cohorts, respectively. For LNM positive/LVSI positive identification, the proposed model achieved AUC values of 0.895/0.848, 0.806/0.795, and 0.804/0.728 in the training, internal, and external test cohorts, respectively, and better than those of three radiologists (AUC = 0.770/0.648/0.674). The proposed model has potential to help clinicians to identify LNM and LVSI status of EC patients and improve treatment planning. 3 TECHNICAL EFFICACY: Stage 2.

A novel predictive model of lymphovascular space invasion in early-stage endometrial cancer.

To predict lymphovascular space invasion (LVSI) positivity in early-stage (stage 1-2) endometrial cancer (EC) using a predictive model with prognostic factors of EC. We included 461 patients who underwent total hysterectomy and bilateral salpingo-oophorectomy with pelvic-paraaortic lymphadenectomy as the primary treatment for presumed early-stage EC at our clinic between 2010 and 2020. Moreover, all surgical specimens were examined histopathologically for the positivity or negativity of LVSI, and the patients were divided into two groups based on these pathologic outcomes. Age, menopausal status, histological type (type 1-2), histological grade (grades 1-2-3), depth of myometrial invasion, and peritoneal cytology results were recorded and analyzed as clinicopathological and demographic characteristics of the patients. The Loess algorithm determined the relationship between the observed and predicted outcomes. The distinction between the algorithms was evaluated by calculating the C-index. LVSI positivity was significantly associated with advanced age, menopause, type 2 EC, advanced histological grade, malignant peritoneal cytology, cervical involvement, and a tumor exceeding 50% of the myometrial depth (p<0.001, respectively). Remarkably, LVSI was most strongly associated with three explanatory variables: 1- More than 50% myometrial invasion [odds ratio (OR): 3.78; 95% confidence interval (CI): 1.80-7.60], 2- Advanced histological grade [OR=1.98 (1.20-3.20) 95% CI], 3- Malignant peritoneal cytology [OR= 3.06 (1.40-6.30) 95% CI]. The penalized maximum likelihood estimation model correctly classified 87% of the included patients (C-index: 0.876). Our predictive model may help predict LVSI based on different prognostic factors. The prognostic factors included in the nomogram were significantly associated with LVSI, particularly myometrial invasion depth of more than 50%, advanced histological grade, and malignant peritoneal cytology.

Accuracy of MRI in predicting deep myometrial invasion in endometrial cancer and the influence of leiomyoma, adenomyosis and the microcystic elongated and fragmented tumour pattern.

The most common form of endometrial cancer is Type 1 endometrioid adenocarcinoma. Depth of myometrial invasion is the most important prognostic factor correlating with overall patient survival. The objective was to investigate how accurate magnetic resonance imaging (MRI) is in predicting the depth of myometrial invasion in preoperative assessment, and the influence of leiomyoma and/or adenomyosis, or microcystic, elongated and fragmented (MELF) pattern of invasion on MRI diagnostic performance. Retrospective audit of 235 endometrial cancer patients from the regional Gynaecology Oncology multidisciplinary meeting at Auckland City Hospital, between January 2020 and January 2021. Radiologist assigned stage was compared to histopathology. Presence of leiomyoma, adenomyosis andMELF pattern evaluated followed by analysis under a Biostatistician's supervision. Overall MRI diagnostic accuracy for depth of myometrial invasion was 86%. For deep myometrial invasion, MRI had a sensitivity of 72% and specificity 91%. Out of the misreported 32/235 cases, 16 demonstrated fibroids and/or adenomyosis leading to a sensitivity of 57% and specificity 93% for deep invasion, compared with 94% and 74% respectively in the population without, demonstrating statistical significance. Thirty seven cases with MELF pattern of invasion showed a sensitivity of 81% and specificity 80% for deep invasion, compared with 63% and 92% respectively in the group without, demonstrating no statistical significance. MRI assessment of the depth of myometrial invasion in endometrial cancer has high accuracy. In the presence of background uterine fibroids/adenomyosis, pre-operative MRI accuracy of evaluating deep invasion shows a statistically significant reduction.

Mismatch repair gene MSH6 correlates with the prognosis, immune status and immune checkpoint inhibitors response of endometrial cancer.

Many patients treated with immune checkpoint inhibitors (ICIs) developed primary or secondary drug resistance for unknown reasons. This study investigates whether mismatch repair (MMR) genes are responsible for this therapeutic restriction. We obtained the transcriptional, clinical and single nucleotide polymorphism data for endometrial cancer (EC) from The Cancer Genome Atlas and the immunophenoscore data of EC from The Cancer Immunome Atlas, then analyzed in R to evaluate the relationship between MMR genes and clinicopathological features, prognosis, immune infiltration, immune checkpoint expression and responsiveness to ICIs in EC. We used differentially expressed genes in the MSH6 high and low expression groups to conduct GO and KEGG analyses to explore the impact of MSH6 on the biological functions of EC. Finally, we verified the bioinformatics results with in vitro experiments. Our analyses showed that compared with the high MSH6 expression group, the low MSH6 expression group had better survival outcomes and less aggressive clinicopathological features. In the multivariate Cox analysis, MSH6 was the only independent risk factor that could predict the prognosis of EC. Besides, the low MSH6 expression group also had a higher immune score, more active immune infiltration and higher immune checkpoint expression, resulting in better responsiveness to ICIs treatment, consistent with the enrichment of GO terms and KEGG pathways related to immune response in this group. Meanwhile, the GO and KEGG enrichment results of the MSH6 high expression group were associated with cell cycle, DNA damage repair and tumorigenesis. To exclude the influence of MSH6 mutations, we performed the previous analyses on the MSH6 wild-type tumor samples and obtained consistent results. In vitro experiments also confirmed that after knocking down MSH6 in endometrial cancer cells, their proliferation, migration and invasion abilities were weakened, while the expression levels of PD-L1 and PD-L2 were elevated. In comparison, overexpression of MSH6 showed an opposite trend. Reduced MSH6 expression could serve as a potential biomarker for predicting better prognosis, active immune status, higher immune checkpoint expression level and better responsiveness to ICIs treatment in EC. MSH6 may become a potential target for treating solid tumors.

Kisspeptin Regulates Cell Invasion and Migration in Endometrial Cancer.

Kisspeptin (a product of the KISS1 gene and its receptor) plays an important role in obstetrics, gynecology, and cancer cell metastasis and behavior. In hypothalamic-pituitary-gonadal axis and placentation, Kisspeptin/Kisspeptin receptor affects hormone release and represses trophoblast invasion into maternal deciduae. Endometrial cancer is one of the common gynecological cancers and is usually accompanied by metastasis, the risk factor that causes death. Recently, research has demonstrated that Kisspeptin/Kisspeptin receptor expression in aggressive-stage endometrial cancer tissues. However, the detailed mechanism of Kisspeptin/Kisspeptin receptor in regulating the motility of endometrial cancers is not well understood. In this study, we use endometrial cancer cell lines RL95-2, Ishikawa, HEC-1-A, and HEC-1-B as models to explore the molecular mechanism of Kisspeptin on cell motility. First, we discovered that Kisspeptin/Kisspeptin receptor was expressed in endometrial cancer cells, and Kisspeptin significantly regulated the migration and invasion of endometrial cancer cells. Furthermore, we explored the epithelial-mesenchymal transition marker expression and the underlying signals were regulated on Kisspeptin treatment. In conclusion, we suggest that Kisspeptin regulates endometrial cancer cell motility via FAK and Src expression and the ERK1/2, N-Cadherin, E-Cadherin, beta-Catenin, Twist, and matrix metalloproteinase signaling pathways. We expect these molecules could be candidates for the development of new approaches and therapeutic targets.

Retrospective analysis of the 18F-FDG PET/CT cutoff value for metabolic parameters was performed as a prediction model to evaluate risk factors for endometrial cancer

PurposeThe study retrospectively analyzed the accuracy and predictive ability of preoperative integrated whole-body 18F-FDG PET/CT for the assessment of high-risk factors in patients with endometrial carcinoma (EC).Materials and methodsA total of 205 patients with endometrial cancer who underwent preoperative PET/CT at Shanghai General Hospital from January 2018 to December 2021 were retrospectively evaluated and last follow-up was June 2023. Our study evaluated the ability and optimal cutoff values of three metabolic and volumetric parameters—standardized uptake value (SUV), metabolic tumor volume (MTV) and total lesion glycolysis (TLG)—to predict deep myometrial invasion (DMI), endocervical stroma invasion (ESI) and lymph node metastases (LNM) in endometrial cancer. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET/CT were used to assess the diagnostic performance for the prediction.ResultsOur study demonstrated a significant relationship between SUVmax (11.29, 17.38, 9.47), SUVmean (5.20, 6.12, 4.49), MTV (38.15, 36.28, 33.79 ml), and TLG (199.30, 225.10, 156.40 g) on PET/CT and histologically confirmed DMI, ESI and LNM in endometrial carcinoma (EC), with sensitivity, specificity, accuracy, PPV, and NPV of 100%/100%/100%, 96.53%/98.89%/87.14%, 97.56%/99.02%/91.22%, 92.42%/92.85%/78.31%, and 100%/100%/100%, respectively. Our study showed a risk model based on optimal cutoff values for MTV and TLG of 19.6 ml/126.3 g, 20.54 ml/84.80 g and 24 ml/49.83 g to preoperatively predict DMI, ESI, and LNM, respectively, in endometrial carcinoma. The 4-year OS (HR) for Stage IA, IB, II, III and IV according to 2009 FIGO was 98.00% (0.22), 95.20% (0.04), 83.90% (0.18), 90.50% (0.09) and 60% (0.51). Accordingly, estimated 4-year DFS (HR) for the stage IA-III was 98% (0.02), 95.20% (0.05), 76.90% (0.27) and 76.30% (0.35), all the patients in stage IV occurred recurrence and progression.ConclusionThe present study showed patients with MTV > = 19.6 ml of MI and PET- positive LN with MTV cutoff > = 24 ml tended to predict poor OS and PFS in endometrial carcinoma. The cutoff of MTV and TLG in PET/CT assessment could be an independent prognostic factors to predict aggressive forms of EC.Graphic

Reducing the Invasiveness of Low- and High-Grade Endometrial Cancers in Both Primary Human Cancer Biopsies and Cell Lines by the Inhibition of Aquaporin-1 Channels.

Aquaporin (AQP) channels in endometrial cancer (EC) cells are of interest as pharmacological targets to reduce tumor progression. A panel of compounds, including AQP1 ion channel inhibitors (AqB011 and 5-(phenoxymethyl) furan-2-carbaldehyde, PMFC), were used to test the hypothesis that inhibition of key AQPs can limit the invasiveness of low- and high-grade EC cells. We evaluated the effects on transwell migration in EC cell lines (Ishikawa, MFE-280) and primary EC cells established from surgical tissues (n = 8). Quantitative PCR uncovered classes of AQPs not previously reported in EC that are differentially regulated by hormonal signaling. With estradiol, Ishikawa showed increased AQPs 5, 11, 12, and decreased AQPs 0 and 4; MFE-280 showed increased AQPs 0, 1, 3, 4, 8, and decreased AQP11. Protein expression was confirmed by Western blot and immunocytochemistry. AQPs 1, 4, and 11 were colocalized with plasma membrane marker; AQP8 was intracellular in Ishikawa and not detectable in MFE-280. AQP1 ion channel inhibitors (AqB011; PMFC) reduced invasiveness of EC cell lines in transwell chamber and spheroid dispersal assays. In Ishikawa cells, transwell invasiveness was reduced ~41% by 80 µM AqB011 and ~55% by 0.5 mM 5-PMFC. In MFE-280, 5-PMFC inhibited invasion by ~77%. In contrast, proposed inhibitors of AQP water pores (acetazolamide, ginsenoside, KeenMind, TGN-020, IMD-0354) were not effective. Treatments of cultured primary EC cells with AqB011 or PMFC significantly reduced the invasiveness of both low- and high-grade primary EC cells in transwell chambers. We confirmed the tumors expressed moderate to high levels of AQP1 detected by immunohistochemistry, whereas expression levels of AQP4, AQP8, and AQP11 were substantially lower. The anti-invasive potency of AqB011 treatment for EC tumor tissues showed a positive linear correlation with AQP1 expression levels. In summary, AQP1 ion channels are important for motility in both low- and high-grade EC subtypes. Inhibition of AQP1 is a promising strategy to inhibit EC invasiveness and improve patient outcomes.

MiR-429 Suppresses Endometrial Cancer Progression and Drug Resistance via DDX53.

(1) Background: To examine miR-429-meditated DEAD (Asp-Glu-Ala-Asp) box polypeptide 53 (DDX53) function in endometrial cancer (EC). (2) Methods: DDX53 and miR-429 levels were measured using quantitative real-time polymerase chain reaction and western blotting assays, cell invasion and migration using Transwell invasion and wound healing assays, and cell proliferation using colony-forming/proliferation assays. A murine xenograft model was also generated to examine miR-429 and DDX53 functions in vivo. (3) Results: DDX53 overexpression (OE) promoted key cancer phenotypes (proliferation, migration, and invasion) in EC, while in vivo, DDX53 OE hindered tumor growth in the murine xenograft model. Moreover, miR-429 was identified as a novel miRNA-targeting DDX53, which suppressed EC proliferation and invasion. (4) Conclusions: DDX53 and miR-429 regulatory mechanisms could provide novel molecular therapies for EC.

Expression and clinical significance of HER2/neu, aromatase P450 and adhesion molecule CD24 in endometrial cancer.

This study aimed at exploring the expression and clinical significance of aromatase P450, adhesion molecule CD24 and HER2/neu in endometrial cancer. The expression of aromatase P450, adhesion molecule CD24 and HER2/neu was detected by immunohistochemistry in 15 cases of endometrial hyperplasia group, 50 cases of endometrial adenocarcinoma and 3 cases of uterine papillary adenocarcinoma, with 15 cases of normal endometrium as control group. We detected no expression of aromatase P450, adhesion molecule CD24 or HER2/neu in control group. Aromatase P450 positive expression rate was 66.7% in endometrial hyperplasia group and 70.3% in endometrial carcinoma group, without significant difference (p>0.05). There was no significant difference (p>0.05) in the positive expression rate of aromatase P450 between different myometrial invasion groups of endometrial adenocarcinomas. CD24 positive expression rate was 40.0% in endometrial hyperplasia group and 79.6% in endometrial carcinoma group, with significant difference (p<0.05). HER2/neu positive expression rate was 26.7% in the endometrial hyperplasia group and 57% in endometrial carcinoma group, with significant difference (p<0.05). In conclusion, aromatase P450 may be one factor associated with endometrial cancer cell proliferation, while CD24 and HER2/neu may be important factors associated with the invasion and metastasis of endometrial cancer.

Development and external validation of a clinical-radiomics nomogram for preoperative prediction of LVSI status in patients with endometrial carcinoma.

To develop and validate a model that incorporates radiomics based on MRI scans and clinical characteristics to predict lymphovascular invasion (LVSI) in endometrial cancer (EC) patients. There were 332 patients with EC enrolled retrospectively in this multicenter study. Radiomics score (Radscore) were computed using the valuable radiomics features. The independent predictors of LVSI were identified by univariate logistic analysis. Multivariate logistic regression was used to develop a clinical-radiomics predictive model. Based on the model, a nomogram was developed and validated internally and externally. The nomogram was evaluated with discrimination, calibration, decision curve analysis (DCA), and clinical impact curves (CIC). Three predictive models were constructed based on clinicopathological features, radiomic factors and a combination of them, and that the clinic-radiomic model performed best among the three models. Four independent factors comprised the clinical-radiomics model: dynamic contrast enhancement rate of late arterial phase (DCE2), deep myometrium invasion (DMI), lymph node metastasis (LNM), and Radscore. Clinical-radiomics model performance was 0.901 (95% CI 0.84-0.96) in the training cohort, 0.80 (95% CI 0.68-0.92) in the internal validation cohort, and 0.81 (95% CI 0.73-0.9) in the external validation cohort for identifying patients with LVSI, respectively. The model is used to develop a nomogram for clinical use. The MRI-based radiomics nomogram could serve as a noninvasive tool to predict LVSI in EC patients.

Non-SMC Condensin I Complex Subunit G Promotes the Proliferation, Invasion and Homologous Recombination Repair of Endometrial Cancer Through PI3K/AKT Signaling Pathway

This study aimed to investigate the role of Non-SMC condensin I complex subunit G (NCAPG) in endometrial cancer (EC) progression and prognosis. The researchers utilized various techniques, including analysis of The Cancer Genome Atlas (TCGA) database, immunohistochemistry, qRT-PCR, Western blotting, and functional assays to assess the impact of NCAPG on EC cells. The TCGA analysis revealed that NCAPG was significantly associated with overall survival and disease-free survival in EC patients. Immunohistochemistry analysis further confirmed a positive correlation between NCAPG expression, histological grade, and myometrial invasion in EC tissues. In vitro experiments demonstrated that NCAPG promoted EC cell proliferation, invasion, and influenced the G1/S cell cycle transition. Additionally, NCAPG was found to regulate the expression of FANCD2 and RAD51 in the homologous recombination repair pathway, and its knockdown sensitized EC cells to poly (ADP-ribose) polymerase inhibitors. The study also revealed the involvement of the PI3K/AKT signaling pathway in mediating the effects of NCAPG on EC cells’ proliferation, invasion, and homologous recombination repair. In conclusion, NCAPG acts as an oncogene in EC, driving proliferation, invasion, and homologous recombination repair through the PI3K/AKT pathway. NCAPG expression correlates with EC prognosis, revealing its significance as a therapeutic target for advanced cases, illuminating EC progression mechanisms.

O‑GlcNAcylation mediates endometrial cancer progression by regulating the Hippo‑YAP pathway.

The incidence of endometrial cancer (EC) is rapidly increasing worldwide. The majority of endometrial cancers are diagnosed at an early stage and are associated with a good prognosis; however, patients with advanced‑stage EC have a poor prognosis and present with invasive metastasis. The mechanisms responsible for the invasion and metastasis of endometrial cancer remain unknown. Here, the present study aimed to examine the effects of O‑GlcNAcylation on the malignancy of EC and its association with Yes‑associated protein (YAP). It was found that the expression of O‑GlcNAc transferase (OGT) and O‑GlcNAcylation were increased in EC tissues; the decrease in O‑GlcNAcylation levels was found to lead to the decreased proliferation, migration and invasion of EC cells. Mass spectrometric analysis revealed that OGT knockdown reduced the O‑GlcNAcylation of YAP. Furthermore, it was found that the reduction in the O‑GlcNAcylation of YAP promoted its phosphorylation, which in turn inhibited the access of YAP to the nucleus and downstream target gene activation, demonstrating that the level of O‑GlcNAcylation affects the development of EC. On the whole, the findings of the present study indicate that YAP is a key molecule linking the O‑GlcNAcylation and Hippo pathways, which together regulate the progression of EC.

Preoperative prediction of lymphovascular space invasion in endometrioid adenocarcinoma: an MRI-based radiomics nomogram with consideration of the peritumoral region.

Lymphovascular space invasion (LVSI) of endometrial cancer (EC) is a postoperative histological index, which is associated with lymph node metastases. A preoperative acknowledgement of LVSI status might aid in treatment decision-making. To explore the utility of multiparameter magnetic resonance imaging (MRI) and radiomic features obtained from intratumoral and peritumoral regions for predicting LVSI in endometrioid adenocarcinoma (EEA). A total of 334 EEA tumors were retrospectively analyzed. Axial T2-weighted (T2W) imaging and apparent diffusion coefficient (ADC) mapping were conducted. Intratumoral and peritumoral regions were manually annotated as the volumes of interest (VOIs). A support vector machine was applied to train the prediction models. Multivariate logistic regression analysis was used to develop a nomogram based on clinical and tumor morphological parameters and the radiomics score (RadScore). The predictive performance of the nomogram was assessed by the area under the receiver operator characteristic curve (AUC) in the training and validation cohorts. Among the features obtained from different imaging modalities (T2W imaging and ADC mapping) and VOIs, the RadScore had the best performance in predicting LVSI classification (AUCtrain = 0.919, and AUCvalidation = 0.902). The nomogram based on age, CA125, maximum anteroposterior tumor diameter on sagittal T2W images, tumor area ratio, and RadScore was established to predict LVSI had AUC values in the training and validation cohorts of 0.962 (sensitivity 94.0%, specificity 86.0%) and 0.965 (sensitivity 90.0%, specificity 85.3%), respectively. The intratumoral and peritumoral imaging features were complementary, and the MRI-based radiomics nomogram might serve as a non-invasive biomarker to preoperatively predict LVSI in patients with EEA.

Lymphovascular Space Invasion in Early-Stage Endometrial Cancer (LySEC): Patterns of Recurrence and Predictors. A Multicentre Retrospective Cohort Study of the Spain Gynecologic Oncology Group.

The main aim is to compare oncological outcomes and patterns of recurrence of patients with early-stage endometrioid endometrial cancer according to lymphovascular space invasion (LVSI) status. The secondary objective is to determine preoperative predictors of LVSI. We performed a multicenter retrospective cohort study. A total of 3546 women diagnosed with postoperative early-stage (FIGO I-II, 2009) endometrioid endometrial cancer were included. Co-primary endpoints were disease-free survival (DFS), overall survival (OS), and pattern of recurrence. Cox proportional hazard models were used for time-to-event analysis. Univariate and multivariate logistical regression models were employed. Positive LVSI was identified in 528 patients (14.6%) and was an independent prognostic factor for DFS (HR 1.8), OS (HR 2.1) and distant recurrences (HR 2.37). Distant recurrences were more frequent in patients with positive LVSI (78.2% vs. 61.3%, p < 0.01). Deep myometrial invasion (OR 3.04), high-grade tumors (OR 2.54), cervical stroma invasion (OR 2.01), and tumor diameter ≥ 2 cm (OR 2.03) were independent predictors of LVSI. In conclusion, in these patients, LVSI is an independent risk factor for shorter DFS and OS, and distant recurrence, but not for local recurrence. Deep myometrial invasion, cervical stroma invasion, high-grade tumors, and a tumor diameter ≥ 2 cm are independent predictors of LVSI.

Diagnostic accuracy of MRI for evaluating myometrial invasion in endometrial cancer: a comparison of MUSE-DWI, rFOV-DWI, and DCE-MRI.

To compare the image quality of high-resolution diffusion-weighted imaging (DWI) using multiplexed sensitivity encoding (MUSE) versus reduced field-of-view (rFOV) techniques in endometrial cancer (EC) and to compare the diagnostic performance of these techniques with that of dynamic contrast-enhanced (DCE) MRI for assessing myometrial invasion of EC. MUSE-DWI and rFOV-DWI were obtained preoperatively in 58 women with EC. Three radiologists assessed the image quality of MUSE-DWI and rFOV-DWI. For 55 women who underwent DCE-MRI, the same radiologists assessed the superficial and deep myometrial invasion using MUSE-DWI, rFOV-DWI, and DCE-MRI. Qualitative scores were compared using the Wilcoxon signed-rank test. Receiver operating characteristic analysis was performed to compare the diagnostic performance. Artifacts, sharpness, lesion conspicuity, and overall quality were significantly better with MUSE-DWI than with rFOV-DWI (p < 0.05). The area under the curve (AUC) of MUSE-DWI, rFOV-DWI, and DCE-MRI for the assessment of myometrial invasion were not significantly different except for significantly higher AUC of MUSE-DWI than that of DCE-MRI for superficial myometrial invasion (0.76 for MUSE-DWI and 0.64 for DCE-MRI, p = 0.049) and for deep myometrial invasion (0.92 for MUSE-DWI and 0.80 for DCE-MRI, p = 0.022) in one observer, and that of rFOV-DWI for deep myometrial invasion in another observer (0.96 for MUSE-DWI and 0.89 for rFOV-MRI, p = 0.048). MUSE-DWI exhibits better image quality than rFOV-DWI. MUSE-DWI and rFOV-DWI shows almost equivalent diagnostic performance compared to DCE-MRI for assessing superficial and deep myometrial invasion in EC although MUSE-DWI may be helpful for some radiologists.

Correction: The Effect of Adenomyosis in Myometrial Invasion and Overall Survival in Endometrial Cancer.

Correction: The Effect of Adenomyosis in Myometrial Invasion and Overall Survival in Endometrial Cancer.

Relationship between molecular markers and lymphadenectomy and lymphovascular space invasion in endometrial cancer.

Relationship between pathologic parameters, surgical parameters, or lymph node status with oncologic outcomes is not fully elucidated in endometrial cancer (EC). We want to investigate the molecular classification of uterine cancer in the Turkish population and its relationship between lymphadenectomy and lymph node metastasis. In this study, 100 patients' clinical and pathologic data diagnosed with EC were analyzed. Pathologic and molecular parameters were investigated and compared them with clinical parameters. According to the molecular analysis, 16 patients (16%) had p53 mutation, 3 patients (3%) were classified as POLE mutant group, 38 (38%) patients in the MSI group, and the remaining 43 patients (43%) into the no specific mutation profile (NSMP) group. Lymph node metastasis rate was significantly higher in copy number high (CNH) group compared to the others. In the CNH group, 29 of 437 (6.6%) dissected lymph nodes had metastasis. The median OS was the highest in the POLE group (72months) and lowest in the CNH group (36months). Endometrial cancer patients showed significantly different overall and disease-free survival according to the molecular subtypes and it was consistent with the literature, Lymph node metastasis risk was the highest in CNH group. MSI status is important for the lymph node metastasis risk but not all abnormalities, especially PMS2 and MLH1 expression changes showed the highest risk.