Depth Of Myometrial Invasion Research Articles

Molecular Genetic Factors of Risk Stratification of Lymph Node Metastasis in Endometrial Carcinoma

Background: According to epidemiological studies, endometrial carcinoma is one of the most frequently diagnosed malignancies of the female reproductive system, with an increasing incidence. Currently, the risk stratification of this neoplasm takes into account the stage, degree of tumor differentiation, histological type and depth of myometrial invasion. Since the publication of the last International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer in 2009, numerous reports have appeared on the molecular characteristics of different types of endometrial carcinoma. Taking this into account, the FIGO Committee determined in 2023 that changes and updates to the staging system are justified to reflect new information about this tumor. Due to the high prevalence of the disease and mortality from endometrial cancer, an in-depth study of the molecular genetic characteristics of tumor cells is relevant; the results of such studies can be used to improve the efficiency of diagnosis, assess the risk of metastasis and prognosis of the disease. Lymph node assessment is crucial for the choice of treatment strategy for endometrial cancer, since metastatic lymph node involvement is one of the main factors affecting prognosis. At the same time, the criteria for the appropriateness of lymphadenectomy in low-differentiated malignant tumors are not clearly defined. Various molecular methods have been proposed to assess the status of lymph nodes; candidate genes are being studied as potential diagnostic biomarkers, as well as microRNA. The aim of the study was to analyze the literature data on numerous studies of molecular risk factors for progression in endometrioid carcinoma, as well as to preserve the most important marker changes in relation to the prognostic development of this disease. Methods: A literature review was conducted using data from the electronic databases PubMed, Google Scholar, and Wiley Cochrane Library for the period from 2018 to 2023 using the specific keywords. Results: The current scientific genetic studies on metastasis and prognostic factors in uterine cancer were analyzed, and a systematization of the reviewed data from the modern literature was done. Conclusions: To select the most effective treatment - intraoperative, adjuvant or combination therapy, minimize postoperative risks of lymphadenectomy and clearly predict the results - further study of the molecular genetic features of endometrial cancer is necessary.

Analysis of Clinicopathological and Molecular Features of Microcystic, Elongated, and Fragmented Pattern Invasion in Endometrioid Endometrial Cancer.

Background: Microcystic, elongated, and fragmented (MELF) invasion is a special invasion pattern in endometrioid endometrial cancer (EEC). This study aimed to investigate the clinical, pathological, and molecular features of the MELF pattern and its prognostic value in patients with EEC. Materials and Methods: The clinical and pathological data of 342 patients with EEC were retrospectively collected at Peking University People's Hospital from January 2019 to December 2022. Some key clinicopathological features were evaluated, including the tumor grade, Federation of Gynecology and Obstetrics (FIGO) staging, cervical stromal involvement, lymph node status, and lymphatic vascular space infiltration (LVSI). Immunohistochemical staining and molecular tests were performed, and the relevant literature was reviewed. Results: The MELF pattern was more prevalent in low-grade EEC. A significant correlation was found between the MELF pattern and advanced FIGO staging, LVSI, the depth of myometrial invasion, cervical stromal involvement, and lymph node metastasis (LNM). The incidence of mismatch-repair-deficient (MMRd) proteins was much higher in the MELF group than in the no-MELF group. Molecular testing revealed that, after copy number-low (CNL), microsatellite instability-high (MSI-H) was the second-most frequent subtype in the MELF group. The recurrence risk did not significantly differ between the MELF and no-MELF groups, but the differences among the four molecular subtypes were statistically significant. However, the MELF group experienced a shorter recurrence time. Among the four molecular subtypes, the recurrence risk was the highest in the CNH subgroup, followed by the MSI-H subgroup. Conclusions: MELF is a special invasion pattern in EEC and is associated with distinct clinicopathological and molecular characteristics, including the latest 2023 FIGO staging. Further research is warranted to explore its implications for treatment strategies and patient outcomes.

Accuracy of intraoperative frozen section in surgical staging of endometrial cancer

ObjectiveThis study evaluates the role of frozen section (FS) in determining the extent of disease during surgery. Materials and methodsThis study retrospectively analyzed a cohort of patients diagnosed with endometrioid-type endometrial cancer between 2019 and 2022 who underwent surgical intervention. The frozen section (FS) results were compared with the final pathology reports, focusing on tumor grade, depth of myometrial invasion, cervical involvement, and tumor diameter. ResultsThe final analysis included 187 patients. The predictive accuracy of FS in determining PS results was 85.6 % for endometrioid histology, 95.7 % for grade 3 tumors, 90.2 % for depth of myometrial invasion, 89.7 % for cervical involvement, and 95.9 % for tumor diameter. Notably, 9.8 % of cases initially classified as grade 1 intraoperatively were upgraded with the final pathology. Similarly, 6.3 % of grade II cases were upgraded, while 60.4 % were downgraded. ConclusionOur study highlights the effectiveness of FS as a dependable tool for assessing endometrial carcinomas and guiding surgical staging decisions. By utilizing FS, the risk of unnecessary surgeries and associated morbidity in patients can be reduced.

Instrumental Diagnosis of Placenta Accreta and Obstetric and Perinatal Outcomes: Literature Review and Observational Study.

Placenta accreta (PA) is a condition where the placenta is pathologically adherent to the uterus due to a defect in the basal decidua with myometrium invasion by chorionic villi and is classified based on the depth of myometrial invasion by histology. However, ultrasound and magnetic resonance imaging have excellent accuracy. In this study, we investigated clinical benefits of early instrumental diagnosis of PA, especially in reducing maternal-fetal complications and improving perinatal outcomes. We also evaluated diagnostic accuracy of ultrasound and magnetic resonance imaging on placental invasiveness assessment. In this review and observational retrospective study, risk factors of PA were collected, and pregnant women underwent third-trimester ultrasound and magnetic resonance imaging (MRI) to evaluate the degree of infiltration. Imaging results compared to histological findings and surgical evaluation. A total of 38 patients were diagnosed with at the University Hospital "San Giovanni di Dio and Ruggi d'Aragona", Salerno, Italy, by second-trimester ultrasound with high sensitivity (100%) and accuracy (86%). Moreover, 37 of them performed MRI and 60.5% were diagnosed with Accreta, 7.9% increta, 10.5% percreta, and 21.1% not accrue with high sensitivity (100%), specificity (88.9%), and accuracy (97.4%). Histological assay confirmed MRI findings in 96.7% of cases. Risk factors of PA were age >35 years and previous CT scans. In unborn babies, mean 1-min Apgar was 4.3 (range, 3-6), and mean 5-min Apgar was 7.13 (range, 7-9). MRI could be a not-invasive, specific, sensitive, and accurate diagnostic tool for assessing the degree of infiltration in PA, and could guide clinical decisions, such as delivery plan, thus reducing perioperative and fetal complications.

The Impact of Positive Peritoneal Cytology on the Survival of Endometrial Cancer Patients

Background: Since the revision of the FIGO staging of endometrial cancer in 2009, patients with positive peritoneal cytology are no longer upstaged to stage IIIA. However, several studies demonstrated poorer outcomes in patients with positive washings. We conducted a survival analysis with the aim of evaluating the impact of positive peritoneal cytology on the survival of EC patients. Methods: We performed a retrospective analysis of prospectively collected data on patients with endometrial cancer operated in our institution between 2008 and 2014. We analysed the impact of positive peritoneal cytology and other established prognostic factors on survival. Results: A total of 227 patients with a median follow-up of 6.9 years were included in the study. A total of 12.8% had positive peritoneal cytology. Positive peritoneal cytology was significantly associated with worse overall survival (HR 1.82; 95% CI 1.02–3.26; p 0.043) but not with worse recurrence-free survival (HR 1.64; 95% CI 0.92–2.93; p 0.091) in univariate analyses. In addition, tumour stage, histologic subtype, lymphovascular space invasion, grade, and the depth of myometrial invasion were all significant prognostic factors for overall survival in univariate analyses. In multivariate survival analysis, only the histologic subtype, tumour stage, and myometrial invasion remained in the model at the last step. Conclusions: Positive peritoneal cytology was associated with worse overall survival in our series of endometrial cancer patients. However, other traditional prognostic factors had a more important prognostic role for survival in a multivariate model.

Angiogenesis in endometrial cancer: clinical and biological significance

Objective: to summarize the available data on the features of vascularization of endometrioid adenocarcinoma (EAC). Material and Methods. The search for relevant sources was performed in the “PubMed” database using the keywords “endometrium + cancer + angiogenesis”, “endometrium + cancer + angiogenesis + lymph”. Of the selected sources, 78 were included in this review. Results. Angiogenesis is an important and necessary stage in the pathogenesis of the appearance, progression and metastasis of EAC and, thus, the study of tumor vascularization provides an opportunity to improve diagnosis and personalized approach to treatment. Vascular density correlates with advanced stage of EAC, high grade of malignancy, myometrial invasion, cervical and adnexal lesions, vascular invasion, metastases to lymph nodes (LN), the presence of cancer cells in the peritoneal fluid, low overall survival and survival without tumor progression. There are publications that deny the connection of vascularization with the histological type of tumor, its grade, lymphovascular invasion, lymph node metastases, the depth of myometrial invasion, and these publications even prove that microvessel density is not an independent prognostic factor. So, there is still no consensus and final opinion, as evidenced by low or high vascularization of EAC. Recently, there are many drugs that affect both the processes of angiogenesis directly and the inducers and factors that control vascular growth. Unfortunately, all such drugs have a fairly high toxicity, and resistance to them very quickly develops. Conclusion. Despite numerous results of studies devoted to the study of the formation of blood vessels and isolated data on lymphangiogenesis in EAC, there is no data in the literature on studying changes in the vascularization of LN in gynecological cancer. However, proangiogenic and antiangiogenic factors are disseminated throughout the body and must exert their effects in distant organs and tissues. Based on changes in the vascularization of LN, it will apparently become possible to predict the activity of angiogenesis in the primary tumor, assess the prognosis of the disease, and the effectiveness of the treatment. In addition, significant expression of the vascular network in an enlarged lymph node biopsied for diagnosis may be a symptom of the development of a malignant tumor in the lymph collection region, even in the absence of metastases.

How deep is too deep? Assessing myometrial invasion as a predictor of distant recurrence in stage I endometrioid endometrial cancer

ObjectivesThe goal of this study was to evaluate the depth of myometrial invasion as a predictor of distant recurrence in patients with node-negative stage IB endometrioid endometrial cancer.MethodsA retrospective multicenter...

Diagnostic utility of apparent diffusion coefficient in preoperative assessment of endometrial cancer: are we ready for the 2023 FIGO staging?

BackgroundAlthough endometrial cancer (EC) is staged surgically, magnetic resonance imaging (MRI) plays a critical role in assessing and selecting the most appropriate treatment planning. We aimed to assess the diagnostic performance of quantitative analysis of diffusion-weighted imaging (DWI) in preoperative assessment of EC.MethodsProspective analysis was done for sixty-eight patients with pathology-proven endometrial cancer who underwent MRI and DWI. Apparent diffusion coefficient (ADC) values were measured by two independent radiologists and compared with the postoperative pathological results.ResultsThere was excellent inter-observer reliability in measuring ADCmean values. There were statistically significant lower ADCmean values in patients with deep myometrial invasion (MI), cervical stromal invasion (CSI), type II EC, and lympho-vascular space involvement (LVSI) (AUC = 0.717, 0.816, 0.999, and 0.735 respectively) with optimal cut-off values of ≤ 0.84, ≤ 0.84, ≤ 0.78 and ≤ 0.82 mm2/s respectively. Also, there was a statistically significant negative correlation between ADC values and the updated 2023 FIGO stage and tumor grade (strong association), and the 2009 FIGO stage (medium association).ConclusionsThe preoperative ADCmean values of EC were significantly correlated with main prognostic factors including depth of MI, CSI, EC type, grade, nodal involvement, and LVSI.

Association between metabolic disorders and clinicopathologic features in endometrial cancer.

In recent years, the incidence of Endometrial cancer (EC) has been on the rise due to high-fat, high-calorie diets and low-exercise lifestyles. However, the relationships between metabolic disorders and the progression of EC remain uncertain. The purpose of our study was to explore the potential association between obesity, hypertension, hyperglycemia and clinicopathologic characteristics in EC patients. In categorical variables, Chi-square tests were used to calculate P values. Univariate logistic regression and multivariate logistic regression were used to identify the risk factors of myometrial invasion>1/2 and lymph node metastasis. Overall survival (OS) was estimated using the Kaplan-Meier method. The study included 406 individuals with EC, 62.6% had type I and 37.4% had type II. Hypertension was seen in 132 (32.5%), hyperglycemia in 75 (18.5%), and overweight or obesity in 217 (53.4%). Hypertension, hyperglycemia, and obesity are strongly associated with the clinicopathologic features of EC. Multivariate logistic regression revealed that hyperglycemia (OR=2.439,95% CI: 1.025-5.804, P = 0.044) was a risk factor for myometrial invasion depth >1/2 in patients with type I EC, and hypertension (OR=32.124,95% CI: 3.287-313.992, P = 0.003) was a risk factor for lymph node metastasis in patients with type I EC. Survival analysis found that hyperglycemia (P < 0.001) and hypertension (P = 0.002) were associated with OS in type I EC. Neither hyperglycemia, hypertension, nor obesity were associated with the prognosis in type II EC. Hyperglycemia was a risk factor for myometrial invasion depth >1/2 in patients with type I EC and hypertension was a risk factor for lymph node metastasis in patients with type I EC. Hypertension and hyperglycemia were associated with poor prognosis in patients with type I EC.

Diagnostic value of transvaginal contrastenhanced ultrasound in identifying benign and malignant endometrial lesions and assessing myometrial invasion.

The objective of this study was to evaluate the diagnostic value of transvaginal contrastenhanced ultrasound (CEUS) in differentiating benign from malignant endometrial lesions and assessing the extent of myometrial invasion. A total of 70 patients who underwent surgery for endometrial lesions at the authors' hospital were selected. Transvaginal ultrasound examination and CEUS were performed for quantitative and qualitative analysis. Based on the CEUS results, an International Federation of Gynecology and Obstetrics (FIGO) disease grade was assigned and compared with pathological findings. Postmenopausal vaginal bleeding is a key clinical manifestation of endometrial carcinoma. Among the patients with endometrial carcinoma, compared with normal myometrium, the lesion areas exhibited a greater rate of rise (defined as enhanced intensity divided by enhancement time) and a shorter half-clearance time (P&lt;0.05). These findings suggest that in endometrial carcinoma, the contrast agent displays a "fast-in/fast-out/hyperenhancement" perfusion pattern. In contrast, the characteristic perfusion pattern for benign endometrial lesions is low enhancement (P&lt;0.05). The diagnostic accuracy of CEUS in detecting myometrial invasion was 88% (22 of 25 cases). Transvaginal CEUS is a practical and effective diagnostic imaging method for distinguishing between benign and malignant endometrial lesions. It can also be used to evaluate the depth of myometrial invasion in patients with early-stage endometrial carcinoma.

THE EFFECT OF TUMOR FREE DISTANCE ON THE PROGNOSTIC FACTORS OF ENDOMETRIAL CANCER

OBJECTIVE: We aimed to evaluate the importance of tumor-free distance (TFD) in prognostic factors of endometrial cancer (EC) and determine the best TFD cut-off value for predicting advanced EC. MATERIAL AND METHODS: This study included 153 patients diagnosed with EC. The depth of myometrial invasion (DOI) and TFD were measured, and the associations between prognostic factors for EC and DOI and TFD were evaluated. RESULTS: The mean ± standard deviation values of TFD and DOI were 12 ± 6 and 7 ± 6 mm, respectively. TFD and DOI were significantly related to lymph node (LN) metastasis, lymphovascular space invasion (LVSI) and cervical involvement. A shorter TFD was significantly associated with a higher tumor grade, positive cytology and LVSI. Shorter DOI was significantly associated with LN metastasis and cervical involvement. A receiver operating characteristics curve analysis demonstrated that the optimal TFD cut-off value was 48% for LN metastasis. A DOI of 47% had the best sensitivity and specificity for LN metastasis. CONCLUSIONS: TFD was superior for predicting LVSI as compared to DOI, whereas DOI showed good diagnostic performance for predicting LN metastasis. Further studies are needed to predict the effect of TFD and DOI on the prognostic factors of endometrial cancer.

New online dynamic nomograms to predict recurrence-free and overall survival after resection of endometrial cancer: a single-institution retrospective cohort study

PurposeThe significant global burden of endometrial cancer (EC) and the challenges associated with predicting EC recurrence indicate the need for a dynamic prediction model. This study aimed to propose nomograms based on clinicopathological variables to predict recurrence-free survival (RFS) and overall survival (OS) after surgical resection for EC.MethodsThis single-institution retrospective cohort study included patients who underwent surgical resection for EC. Web-based nomograms were developed to predict RFS and OS following resection for EC, and their discriminative and calibration abilities were assessed.ResultsThis study included 289 patients (median age, 56 years). At a median follow-up of 51.1 (range, 4.1–128.3) months, 13.5% (39/289) of patients showed relapse or died, and 10.7% (31/289) had non-endometrioid tumors (median size: 2.8 cm). Positive peritoneal cytology result (hazard ratio [HR], 35.06; 95% confidence interval [CI], 1.12–1095.64; P = 0.0428), age-adjusted Charlson comorbidity index (AACCI) (HR, 52.08; 95% CI, 12.35–219.61; P < 0.001), and FIGO (Federation of Gynecology and Obstetrics) stage IV (HR, 138.33; 95% CI, 17.38–1101.05; P < 0.001) were predictors of RFS. Similarly, depth of myometrial invasion ≥ 1/2 (HR, 1; 95% CI, 0.46–2.19; P = 0.995), AACCI (HR, 93.63; 95% CI, 14.87–589.44; P < 0.001), and FIGO stage IV (HR, 608.26; 95% CI, 73.41–5039.66; P < 0.001) were predictors of OS. The nomograms showed good predictive capability, positive discriminative ability, and calibration (RFS: 0.895 and OS: 0.891).ConclusionThe nomograms performed well in internal validation when patients were stratified into prognostic groups, offering a personalized approach for risk stratification and treatment decision-making.

Enhancing Preoperative Assessment of Endometrial Cancer: The Role of Diffusion-Weighted Magnetic Resonance Imaging in Evaluating Myometrial Invasion.

Endometrial cancer (EC) is the most common gynecological malignancy. Accurate preoperative staging is essential for guiding treatment. The depth of myometrial invasion is a key prognostic factor. This prospective study aimed to evaluate the added benefit of diffusion-weighted imaging (DWI) compared to T2-weighted imaging (T2WI) and dynamic contrast-enhanced MRI (DCE-MRI) for the preoperative assessment of myometrial invasion in EC. The aim of this prospective study was to evaluate the added benefit of DWI in the preoperative assessment of myometrial invasion in EC, in comparison with T2WI and DCE-MRI. The objectives were to assess the imaging characteristics of endometrial carcinoma on T2WI, DCE, and DW MR, to assess the depth of myometrial invasion and overall stage in EC patients, to compare the diagnostic performance of DCE-MRI with that of DW-MRI combined with T2WI, to describe how MR imaging findings can be combined with tumor histologic features and grading to guide treatment planning, and to evaluate the pitfalls and limitations of DCE and DW MR in the assessment of EC. Thirty-one patients with histologically confirmed EC underwent preoperative pelvic MRI on a 1.5T scanner. T2WI, DWI (b-values 0, 1000 s/mm2), and DCE-MRI were performed. Two radiologists independently assessed myometrial invasion on T2WI, T2WI + DWI, and T2WI + DCE-MRI. Histopathology after hysterectomy was the reference standard. Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each MRI protocol, with separate analyses for superficial (<50%) and deep (≥50%) myometrial invasions. The accuracy for assessing superficial invasion was 61.3% for T2WI, 87.1% for T2WI + DWI, and 87.1% for T2WI + DCE-MRI. For deep invasion, accuracy was 64.5% for T2WI, 90.3% for T2WI + DWI, and 90.3% for T2WI + DCE-MRI. Sensitivity, specificity, PPV, and NPV for T2WI + DWI and T2WI + DCE-MRI were high and comparable (88.9-91.7%) for both superficial and deep invasions. T2WI had markedly lower sensitivity and specificity. The differences between T2WI and the functional MRI protocols were statistically significant (p < 0.01). DWI and DCE-MRI significantly improve the diagnostic performance of MRI for the preoperative assessment of myometrial invasion depth in EC compared to T2WI alone. DWI + T2WI and DCE-MRI + T2WI demonstrate comparable high accuracy. DWI may be preferable since it is faster and avoids contrast administration.

The Importance of Metabolic Factors in Endometrial Cancer: Evaluating the Utility of the Triglyceride-to-Glycemia Index and Triglyceride-to-High-Density Lipoprotein Ratio As Biomarkers.

Introduction Endometrial cancer (EC) is the most common gynecological malignancy in developed countries worldwide. Its incidence is rising, making it a significant public health concern. The relationship between lipids, hyperglycemia, and anthropometric risk factors in the development of EC has gained increasing attention in recent years. Understanding the role of dyslipidemia as a part of metabolic syndrome is crucial for developing effective prevention and treatment strategies for EC. We investigate the association between dyslipidemia, hyperglycemia, and EC. This study aims to elucidate the potential contribution of altered lipid profiles and chronic hyperglycemia to endometrial carcinogenesis. By analyzing patients with benign and malignant endometrial pathologies, we seek to identify novel biomarkers and unravel the underlying mechanisms by which these metabolic factors influence the risk of developing EC. Material and methods Our retrospective unicentric study included 390 patients (192 diagnosed with EC and 198 with endometrial hyperplasia), in which we compared the clinical and biochemical characteristics, with a particular focus on lipid profiles and glycemic indices sampled 24-48 hours before surgery. The data obtained from the medical records were analyzed using statistical methods to compare selected metabolic factors between EC and endometrial hyperplasia. Results Our analysis revealed statistically significant differences in metabolic health and lipid profiles between patients diagnosed with EC and those with endometrial hyperplasia. The EC group exhibits trends towards higher levels of triglycerides (TG) and glycated hemoglobin, alongside a higher BMI. Notably, high-density lipoprotein cholesterol levels were lower in the EC group. Conclusion Although the triglycerides-to-fasting blood glucose index and the triglycerides-to-high-density lipoprotein cholesterol ratio did not demonstrate sufficient discriminatory power for predicting myometrial invasion depth in this study, further exploration of cost-effective emerging biomarkers warrants investigation in future studies.

Comparison of Myometrial Invasion Depth Examination Methods in Endometrial Cancer

Comparison of Myometrial Invasion Depth Examination Methods in Endometrial Cancer

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.

The differential expression of AFF3 in cervical cancer and its correlation with clinicopathological features and prognosis

Background Cervical cancer (CC) is the second most common malignancy in women, and identifying biomarkers of CC is crucial for prognosis prediction. Here, we investigated the expression of AF4/FMR2 Family Member 3 (AFF3) in CC and its association with clinicopathological features and prognosis. Methods Tumour and adjacent tissues, along with clinicopathological features and follow-up information, were collected from 78 patients. AFF3 expression was assessed using quantitative real-time polymerase chain reaction and Western blotting. The correlation between AFF3 expression and CC symptoms was using chi-square test. The 5-year overall survival (OS) was analysed using the Kaplan-Meier method. The Univariate analysis of prognostic risk factors was conducted using the COX proportional hazards model, followed by multivariate COX regression analysis including variables with p < 0.01. Results AFF3 expression was downregulated in CC, and its levels were correlated with lymph node metastasis (LNM) and International Federation of Gynaecology and Obstetrics (FIGO) stage. Patients with low AFF3 expression had a lower 5-year OS rate (52.78%, 19/36). Postoperative survival was reduced in patients with histological grade 3 (G3), myometrial invasion (depth ≥ 1/2), lymphovascular space invasion, LNM, and advanced FIGO stage. Low expression of AFF3 (HR: 2.848, 95% CI: 1.144–7.090) and histological grade G3 (HR: 4.393, 95% CI: 1.663–11.607) were identified as independent prognostic risk factors in CC patients. Conclusion Low expression of AFF3 and histological G3 are independent predictors of poor prognosis in CC patients, suggesting that AFF3 could serve as a potential biomarker for prognostic assessment in CC.

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.

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.

Mitochondrial Calcium Uniporter (MCU) that Modulates Mitochondrial Calcium Uptake and Facilitates Endometrial Cancer Progression through Interaction with VDAC1.

Although endometrial cancer represents a frequently diagnosed malignancy of the female reproductive tract, we know very little about the factors that control endometrial cancer. Our study was presented to investigate the function of MCU in endometrial tumorigenesis and the molecular mechanisms involved. A total of 94 endometrial cancer patients were recruited into our cohort. MCU and VDAC1 expression was examined in tumor and normal tissues via immunohistochemistry and immunofluorescence. Associations of MCU and VDAC1 expression with clinicopathological characteristics were evaluated. After transfection with shRNA targeting MCU or full-length MCU plasmids, clone formation, wound healing, transwell and MitoTracker Red staining were separately presented in Ishikawa and RL95-2 cells. Moreover, Western blotting or immunofluorescence was utilized to examine the expression of MCU, VDAC1, Na+/Ca2+/Li+ exchanger (NCLX), and β-catenin under VDAC1 knockdown and/or MCU overexpression or knockdown. MCU and VDAC1 expression were prominently up-regulated in endometrial cancer tissues and were significantly associated with histological grade, depth of myometrial invasion and lymph node status. MCU up-regulation enhanced clone formation, migration, and mitochondrial activity of endometrial cancer cells. The opposite results were investigated when MCU was silenced. MCU or VDAC1 silencing reduced the expression of MCU, VDAC1, NCLX, and β-catenin. Moreover, VDAC1 knockdown alleviated the promoting effect of MCU overexpression on the above proteins. This investigation demonstrated that MCU-induced mitochondrial calcium uptake plays a critical role in endometrial tumorigenesis through interaction with VDAC1.