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Keywords = lymphovascular space invasion

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12 pages, 354 KB  
Article
Association Between MMR Status and Prognostic Pathological Factors in Endometrioid Endometrial Cancer—A Single-Center Retrospective Study
by Cezary Miedziarek, Hubert Bochyński, Katarzyna Bociańska, Michał Potograbski, Piotr Tyburski, Mikołaj Piotr Zaborowski and Ewa Nowak-Markwitz
Cancers 2025, 17(22), 3605; https://doi.org/10.3390/cancers17223605 - 8 Nov 2025
Viewed by 361
Abstract
Background/Objectives: Prognostic assessment in endometrial cancer (EC) is based on clinical and pathological features such as histological type, FIGO stage, tumor grade, LVSI, P53 status, and hormone receptor expression. Recent molecular research has distinguished four EC subtypes, with MMR status (pMMR vs. [...] Read more.
Background/Objectives: Prognostic assessment in endometrial cancer (EC) is based on clinical and pathological features such as histological type, FIGO stage, tumor grade, LVSI, P53 status, and hormone receptor expression. Recent molecular research has distinguished four EC subtypes, with MMR status (pMMR vs. dMMR) providing clinically relevant stratification due to its predictive value for immunotherapy. The present study aims to compare dMMR and pMMR tumors in terms of the prevalence of adverse histopathological prognostic factors. Methods: This retrospective study included 179 patients with endometrioid endometrial carcinoma (EEC) treated at the authors’ institution (1 January 2023–31 August 2025). Patients were classified by MMR status (pMMR vs. dMMR) based on immunohistochemistry, and clinicopathological variables, including FIGO stage, myometrial invasion depth, tumor grade, LVSI, ER/PR expression, and P53 status, were analyzed. Normality was assessed using the Shapiro–Wilk test. Categorical variables were tested with chi-square or Fisher’s exact tests, reporting odds ratios with 95% CI, while continuous variables were compared using the Mann–Whitney test and presented as median (IQR) with the Hodges–Lehmann difference and 95% CI. Multivariable logistic regression with Wald tests was performed. Results: dMMR tumors accounted for 29.05% of all cases. Patients in the dMMR group were significantly more likely to present with FIGO stage III/IV disease (p = 0.036) and to exhibit LVSI (p = 0.008). No differences were observed between the groups with respect to tumor grade, estrogen receptor positivity, progesterone receptor positivity, or the prevalence of deep myometrial invasion. The most frequent pattern of protein loss in the dMMR population was concurrent loss of MLH1 and PMS2. Conclusions: In the studied population, dMMR tumors more frequently exhibited adverse prognostic features of EC, such as advanced stage of disease and lymphovascular space invasion. This suggests the potential for effective immunotherapy in this patient group. Full article
(This article belongs to the Section Cancer Pathophysiology)
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14 pages, 2035 KB  
Review
Multidisciplinary Perspective of Spread Through Air Spaces in Lung Cancer: A Narrative Review
by Riccardo Orlandi, Lorenzo Bramati, Maria C. Andrisani, Giorgio A. Croci, Claudia Bareggi, Simona Castiglioni, Francesca Romboni, Sara Franzi and Davide Tosi
Cancers 2025, 17(20), 3374; https://doi.org/10.3390/cancers17203374 - 19 Oct 2025
Viewed by 861
Abstract
Spread Through Air Spaces (STAS) is an emerging pattern of tumor invasion in lung cancer, first recognized by the World Health Organization in 2015. This narrative review examines STAS from a multidisciplinary perspective, integrating pathologic, radiologic, oncologic, and surgical points of view, together [...] Read more.
Spread Through Air Spaces (STAS) is an emerging pattern of tumor invasion in lung cancer, first recognized by the World Health Organization in 2015. This narrative review examines STAS from a multidisciplinary perspective, integrating pathologic, radiologic, oncologic, and surgical points of view, together with molecular biology to assess its clinical significance, diagnostic challenges, and therapeutic implications. Pathologically, STAS is characterized by tumor cells floating beyond the main tumor, contributing to recurrence and poor prognosis. Radiologic advancements suggest potential imaging markers for STAS, such as spiculation, the absence of an air bronchogram, solid tumor components, as well as high fluorodeoxyglucose uptake, though definitive preoperative identification remains challenging. Oncologic studies link STAS to aggressive tumor behavior and lympho-vascular invasion, suggesting a role for adjuvant chemotherapy even in the earliest stages of disease; furthermore, specific molecular alterations have been discovered, including EGFR wild-type status and ALK/ROS1 rearrangements together with high Ki-67 expression, tumor necrosis, and alterations in cell adhesion proteins like E-cadherin. Surgical aspects highlight the increased risk of recurrence following limited resection, raising concerns about optimal surgical strategies. The debate over STAS as a true invasion mechanism versus an artifact from surgical handling underscores the need for standardized pathological evaluation. This review aims to refine STAS detection, integrate it into multidisciplinary treatment decision-making, and assess its potential as a staging criterion in lung cancer management. Full article
(This article belongs to the Special Issue Surgical Management of Non-Small Cell Lung Cancer)
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12 pages, 906 KB  
Article
Clinicopathological Analysis of a Group of Patients Diagnosed with Endometrial Cancer and Mutation in the Tp53 Gene—Single-Center Study
by Dominik Jakubowski, Aleksandra Kukla-Jakubowska, Kaja Michalczyk, Marcin Misiek, Janusz Menkiszak and Anita Chudecka-Głaz
J. Clin. Med. 2025, 14(19), 6809; https://doi.org/10.3390/jcm14196809 - 26 Sep 2025
Viewed by 427
Abstract
Background/Objectives: Endometrial cancer (EC) remains a significant clinical challenge due to increasing incidence and mortality, particularly among patients with TP53 gene mutations, which define a high-risk molecular subtype. This study aimed to characterize the clinicopathological and molecular features of a cohort of [...] Read more.
Background/Objectives: Endometrial cancer (EC) remains a significant clinical challenge due to increasing incidence and mortality, particularly among patients with TP53 gene mutations, which define a high-risk molecular subtype. This study aimed to characterize the clinicopathological and molecular features of a cohort of patients diagnosed with endometrial cancer and confirmed TP53 mutations. Methods: This retrospective single-center study analyzed 20 patients with histologically confirmed EC and pathogenic TP53 mutations treated at the Pomeranian Medical University Clinical Hospital No. 2 between January 2023 and March 2025. Clinical, histological, and molecular data—including FIGO stage, tumor grade, and coexisting mutations—were collected. Results: Patients had a mean age of 69.2 years and a mean BMI of 29.5 kg/m2. The most common histological types were endometrioid (45%) and serous carcinoma (40%). Grade 3 tumors were found in 65% of cases, and 65% of patients exhibited lymphovascular space invasion. Notably, 30% of patients were upstaged under the FIGO 2023 classification when incorporating TP53 mutation status. Four patients had coexisting PIK3CA mutations. No significant differences were observed in BMI, endometrial thickness, or abnormal bleeding between histological subgroups. Conclusions: TP53-mutated endometrial cancers are associated with aggressive histopathological features and advanced staging. Molecular profiling, particularly TP53 mutation assessment, provides essential prognostic information and may inform personalized therapeutic strategies. Larger, multicenter studies are warranted to validate these findings and identify actionable molecular targets. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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14 pages, 800 KB  
Article
The Impact of Lymphovascular Space Invasion on Recurrence and Survival in FIGO Stage I Node-Negative Endometrioid Endometrial Cancer
by Yakup Yalcin, Bahadir Kosan, Serenat Yalcin, Merve Abay and Kemal Ozerkan
J. Clin. Med. 2025, 14(18), 6535; https://doi.org/10.3390/jcm14186535 - 17 Sep 2025
Cited by 2 | Viewed by 846
Abstract
Background/Objective: To evaluate the prognostic impact of lymphovascular space invasion (LVSI) on disease-free survival (DFS) and overall survival (OS) in patients with FIGO 2009 stage I endometrioid endometrial cancer with pathologically negative lymph node involvement. Methods: This retrospective cohort study included [...] Read more.
Background/Objective: To evaluate the prognostic impact of lymphovascular space invasion (LVSI) on disease-free survival (DFS) and overall survival (OS) in patients with FIGO 2009 stage I endometrioid endometrial cancer with pathologically negative lymph node involvement. Methods: This retrospective cohort study included 469 patients with FIGO 2009 stage I node-negative endometrioid endometrial carcinoma who underwent comprehensive surgical staging at a single tertiary center between January 1993 and April 2025. Demographic, clinicopathological, treatment, and follow-up data were collected. Survival outcomes were assessed using Kaplan–Meier analysis, and prognostic factors were identified via univariate and multivariate Cox regression models. Results: LVSI was present in 17.7% of the cohort (n = 83). Patients with LVSI had significantly higher tumor grades, larger tumor size, and deeper myometrial invasion compared to LVSI-negative patients (p < 0.001). Recurrence was more frequent in the LVSI-positive group (14.5% vs. 6.5%, p = 0.026), with distant metastasis predominating (83.3%). The 5-year DFS was 86.4% in the LVSI-positive group versus 96.3% in the LVSI-negative group (p = 0.0020), while the 5-year OS was 72.1% vs. 91.2%, respectively (p = 0.0014). In multivariate analysis, LVSI was an independent prognostic factor for both recurrence (HR = 4.80, 95% CI: 1.62–14.21; p < 0.001) and overall mortality (HR = 3.33, 95% CI: 1.43–7.77; p = 0.012). Conclusions: LVSI is a strong and independent predictor of adverse oncologic outcomes in early-stage, node-negative endometrioid endometrial cancer. Its presence is associated with significantly decreased DFS and OS, particularly due to an increased risk of distant recurrence. These findings support the incorporation of LVSI into contemporary risk stratification and adjuvant treatment algorithms. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Obstetrics and Gynecology Cancers)
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16 pages, 2456 KB  
Article
Comparative Prognostic Evaluation of the Revised International Federation of Gynecology and Obstetrics 2023 and 2009 Staging Systems in Early Endometrial Cancer
by Su Lim Lee, Yu Ri Shin, Hokun Kim and Sung Eun Rha
Cancers 2025, 17(18), 3017; https://doi.org/10.3390/cancers17183017 - 16 Sep 2025
Viewed by 560
Abstract
Background/Objectives: We comparatively evaluated the prognostic performance of the 2009 and 2023 International Federation of Gynecology and Obstetrics (FIGO) staging systems for early-stage endometrial cancer based on histological subtype stratification. Methods: A retrospective cohort of 472 patients with FIGO 2009 stage [...] Read more.
Background/Objectives: We comparatively evaluated the prognostic performance of the 2009 and 2023 International Federation of Gynecology and Obstetrics (FIGO) staging systems for early-stage endometrial cancer based on histological subtype stratification. Methods: A retrospective cohort of 472 patients with FIGO 2009 stage I–II between 2004 and 2019 was analyzed. Patients were restaged using both systems. Overall survival (OS) and recurrence-free survival (RFS) were determined according to histopathological aggressiveness. Kaplan–Meier survival analysis with log-rank testing compared the performance of the systems. Cox proportional hazards regression identified independent prognostic factors. A hypothetical modification of the FIGO 2023 system was evaluated for aggressive subtypes. Results: In all, 388 patients had nonaggressive histology, and 84 patients had aggressive histology. For cases of nonaggressive histology, FIGO 2023 demonstrated superior prognostic discrimination for OS and RFS (p < 0.05), whereas FIGO 2009 showed significant stratification for OS (p < 0.001) but not RFS (p = 0.149). For cases of aggressive histology, FIGO 2009 showed significant stratification for RFS (p = 0.017) but not OS (p = 0.31), whereas FIGO 2023 showed no significant stratification for either endpoint. The hypothetical modification of the FIGO 2023 staging system showed significantly improved discrimination for RFS (p = 0.019) but not OS. Multivariate analysis identified age and lymphovascular space invasion as independent prognostic factors in nonaggressive cancers, whereas cervical stromal involvement was significant in aggressive subtypes. Conclusions: The prognostic utility of the FIGO staging system is histology dependent. Although FIGO 2023 offers enhanced risk stratification for nonaggressive endometrial cancers, its discriminatory power for aggressive subtypes remains limited, indicating the need for histology-specific refinements of future staging frameworks. Full article
(This article belongs to the Special Issue Survivorship and Quality of Life in Endometrial Cancer)
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13 pages, 776 KB  
Article
Improved Prognostic Stratification with the FIGO 2023 Staging System in Endometrial Cancer: Real-World Validation in 2969 Patients
by Jun-Hyeong Seo, Soo-Min Kim, Yoo-Young Lee, Tae-Joong Kim, Jeong-Won Lee, Byoung-Gie Kim and Chel Hun Choi
Cancers 2025, 17(17), 2871; https://doi.org/10.3390/cancers17172871 - 1 Sep 2025
Viewed by 1218
Abstract
Background/Objectives: To assess the impact of the 2023 FIGO staging revision on stage distribution, survival outcomes, and prognostic performance in endometrial cancer compared to the 2009 system. Methods: This retrospective cohort study analyzed 2969 patients with FIGO 2009 stage I–III endometrial cancer diagnosed [...] Read more.
Background/Objectives: To assess the impact of the 2023 FIGO staging revision on stage distribution, survival outcomes, and prognostic performance in endometrial cancer compared to the 2009 system. Methods: This retrospective cohort study analyzed 2969 patients with FIGO 2009 stage I–III endometrial cancer diagnosed at Samsung Medical Center (1994–2023). Patients were reclassified per the 2023 FIGO system. Stage migration, progression-free survival (PFS), and overall survival (OS) were evaluated. Prognostic performance was compared using the Akaike information criterion (AIC), Bayesian information criterion (BIC), concordance index (C-index), and area under the receiver operating characteristic curve (AUC). Results: Stage migration occurred in 20.2% of patients, with 98.3% involving upstaging from FIGO 2009 stage I, largely due to the inclusion of aggressive histology, p53 abnormality, and substantial lymphovascular space invasion (LVSI). The proportion of stage I tumors decreased from 81.5% to 65.2%, while stage II increased to 21.9%, including 14.8% newly classified as stage IIC. Patients remaining in stage I showed favorable outcomes (5-year PFS: 95.3%, OS: 98.5%), whereas those upstaged—especially to stage IIC—had significantly worse outcomes (5-year PFS: 76.5%, OS: 83.1%). Tumors with p53 abnormalities had poorer survival (PFS: 70.8%, OS: 76.6%). The 2023 FIGO system outperformed the 2009 system in prognostic discrimination across all metrics. Conclusions: The FIGO 2023 staging revision improves prognostic accuracy in endometrial cancer by integrating histopathologic and molecular risk factors. These refinements enhance risk stratification and may support more individualized treatment strategies. Full article
(This article belongs to the Section Cancer Pathophysiology)
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18 pages, 1473 KB  
Article
Neutrophil to Lymphocyte Ratio a Prognostic Tool in Endometrial Cancer Among Classical Prognostic Factors
by Alexandra Timea Kirsch-Mangu, Alexandru Țîpcu, Vlad Alexandru Gâta, Diana Cristina Pop, Zsolt Fekete, Alexandru Irimie and Paul Milan Kubelac
Diagnostics 2025, 15(17), 2172; https://doi.org/10.3390/diagnostics15172172 - 27 Aug 2025
Viewed by 895
Abstract
Background: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Despite advances in diagnosis and treatment, recurrence and mortality remain significant concerns. The neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has shown prognostic value in several malignancies, but its [...] Read more.
Background: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Despite advances in diagnosis and treatment, recurrence and mortality remain significant concerns. The neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has shown prognostic value in several malignancies, but its utility in EC remains underexplored. Objective: To evaluate the prognostic significance of the preoperative NLR in patients with endometrial cancer undergoing primary surgical treatment. Methods: We conducted a retrospective cohort study including 398 patients with histologically confirmed endometrial adenocarcinoma surgically treated at a tertiary cancer center. Preoperative complete blood counts were used to calculate NLR, and a cutoff value of 2.27 was determined through Receiver Operating Characteristic (ROC) analysis. Survival outcomes were assessed using Kaplan–Meier analysis and Cox proportional hazards modeling. Results: Patients with NLR ≥ 2.27 had significantly reduced median overall survival (OS) compared to those with NLR < 2.27 (72.3 vs. 92.8 months, p = 0.008). In multivariate analysis, elevated NLR remained an independent predictor of poorer OS (HR = 1.87; 95% CI: 1.156–3.017; p = 0.011), alongside age ≥ 64 years, lymphovascular space invasion (LVSI), lymph node involvement, and distant metastases. ROC analysis yielded an Area Under the Curve (AUC) of 0.646 for NLR. Notably, vaginal brachytherapy was associated with improved survival (HR = 0.53; p = 0.026), while other adjuvant therapies were not independently significant. Conclusions: Preoperative NLR is an accessible, independent prognostic biomarker in endometrial cancer and may serve as a surrogate indicator of tumor-promoting inflammation and immune dysregulation. Its integration into preoperative assessment could enhance risk stratification and guide personalized treatment strategies. However, findings should be interpreted in light of the study’s retrospective design, single-center setting, and lack of molecular classification data. Prospective validation is warranted to confirm its clinical utility. Full article
(This article belongs to the Special Issue Diagnosis and Management of Gynecological Cancers: Third Edition)
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12 pages, 838 KB  
Article
Impact of Para-Aortic Lymphadenectomy on Clinically FIGO Stage IIIC1 High-Grade Endometrial Cancer: A Retrospective Cohort Study from Two Tertiary Centers in Korea and Taiwan
by Yen-Ling Lai, Jun-Hyeong Seo, Koping Chang, Hyun-Soo Kim, Jung Chen, Tyan-Shin Yang, Yu-Li Chen and Yoo-Young Lee
Medicina 2025, 61(6), 1079; https://doi.org/10.3390/medicina61061079 - 12 Jun 2025
Viewed by 1152
Abstract
Background and Objectives: The therapeutic effect of para-aortic lymphadenectomy in patients with clinically para-aortic node-negative diseases remains controversial. In this study, we investigated whether combined pelvic and para-aortic lymphadenectomy has a survival benefit compared with pelvic lymphadenectomy alone in patients with clinically [...] Read more.
Background and Objectives: The therapeutic effect of para-aortic lymphadenectomy in patients with clinically para-aortic node-negative diseases remains controversial. In this study, we investigated whether combined pelvic and para-aortic lymphadenectomy has a survival benefit compared with pelvic lymphadenectomy alone in patients with clinically FIGO stage IIIC1 high-grade endometrial cancer. Materials and Methods: We retrospectively reviewed patients with clinically FIGO stage IIIC1 high-grade endometrial cancer in the period between January 2000 and December 2020 at two tertiary centers. The patients were stratified according to type of lymphadenectomy and subgroup analyses performed. Kaplan–Meier analysis and a Cox proportional-hazards model were used to evaluate survival outcomes. Results: A total of 56 patients were identified. Of these patients, 18 underwent pelvic lymphadenectomy alone and 38 underwent combined pelvic and para-aortic lymphadenectomy. After staging surgery, 34 (60.7%) patients had pathologically confirmed lymph node metastases. Within a median follow-up of 57.5 months, there were no significant differences in recurrence-free survival (RFS) and overall survival (OS) between the two groups. In subgroup analyses, the node- and lymphovascular space invasion (LVSI)-positive patients characterized by grade 3 endometrioid histologic type (p = 0.010) or negative peritoneal washing cytology (p = 0.035) had an RFS benefit from combined pelvic and para-aortic lymphadenectomy. Conclusions: The addition of para-aortic lymphadenectomy to pelvic lymphadenectomy did not improve survival in patients with clinically FIGO IIIC1 endometrial cancer. However, para-aortic lymphadenectomy may have RFS benefit for patients with grade 3 endometrioid histologic type and positive LVSI. Full article
(This article belongs to the Special Issue Endometrial Cancer: Biomarkers and Management)
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15 pages, 2678 KB  
Systematic Review
Adjuvant Radiotherapy for Intermediate-Risk Early-Stage Cervical Cancer Post Radical Hysterectomy: A Systematic Review and Meta-Analysis
by Pedro Henrique Costa Matos da Silva, Gabriela Oliveira Gonçalves Molino, Maírla Marina Ferreira Dias, Ana Gabriela Alves Pereira, Nicole dos Santos Pimenta, Deivyd Vieira Silva Cavalcante, Ana Clara Felix de Farias Santos, Sarah Hasimyan Ferreira, Rodrigo da Silva Santos and Angela Adamski da Silva Reis
J. Clin. Med. 2025, 14(11), 4002; https://doi.org/10.3390/jcm14114002 - 5 Jun 2025
Cited by 1 | Viewed by 2423
Abstract
Background: The risk of recurrence of early-stage cervical cancer (CC) is associated with prognostic factors such as tumor size, lymphovascular space invasion (LVSI), and deep stromal invasion (DSI). However, the adjuvant pelvic radiotherapy (RT) following surgery to reduce the risk of recurrence in [...] Read more.
Background: The risk of recurrence of early-stage cervical cancer (CC) is associated with prognostic factors such as tumor size, lymphovascular space invasion (LVSI), and deep stromal invasion (DSI). However, the adjuvant pelvic radiotherapy (RT) following surgery to reduce the risk of recurrence in “intermediate risk” remains controversial. This study aims to evaluate the role of adjuvant RT in the recurrence and identify prognostic factors. Methods: A systematic search of PubMed, Embase, and Cochrane databases was performed to identify studies comparing adjuvant RT versus no adjuvant treatment in early-stage CC patients with intermediate-risk factors defined by GOG-92 criteria. Outcomes were recurrence, local recurrence, death, 5-year overall survival (5y-OS), and 5-year disease-free survival (5y-DFS). Tumor size ≥ 4 cm, LVSI, and DSI were also evaluated as prognostic factors for recurrence. Statistical analysis was performed using Review Manager 7.2.0. Heterogeneity was assessed with I2 statistics. Results: A total of 1504 patients from nine studies were included; only one study was a randomized controlled trial, while the others were retrospective cohorts. Adjuvant RT was used to treat 781 patients (52%). Median follow-up ranged from 48 to 120 months. Recurrence (OR 0.75; 95% CI 0.38–1.46; p = 0.39), local recurrence (OR 0.73; 95% CI 0.44–1.20; p = 0.22), death (OR 0.97; 95% CI 0.52–1.80; p = 0.91), 5y-OS (OR 1.22; 95% CI 0.36–4.18; p = 0.75), and 5y-DFS (OR 0.78; 95% CI 0.42–1.43 p = 0.42) revealed no statistically significant differences between adjuvant RT and observation groups. TS ≥ 4 cm was an independent prognostic risk factor for recurrence (HR 1.83; 95% CI 1.12–2.97; p = 0.02). Conclusions: Our findings suggest that adjuvant RT does not reduce recurrence risk in early-stage cervical cancer. Consider TS ≥ 4 cm as a significant prognostic factor for recurrence. Adjuvant RT in intermediate-risk patients should be considered with caution due the lack of significant improvement in recurrence until the CERVANTES and GOG-0263 trial results become available. Full article
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11 pages, 603 KB  
Article
A Nomogram for Preoperative Prediction of Tumor Aggressiveness and Lymphovascular Space Involvement in Patients with Endometrial Cancer
by Riccardo Valletta, Giacomo Avesani, Vincenzo Vingiani, Bernardo Proner, Martin Steinkasserer, Sara Notaro, Francesca Vanzo, Giovanni Negri, Caterina Vercelli and Matteo Bonatti
J. Clin. Med. 2025, 14(11), 3914; https://doi.org/10.3390/jcm14113914 - 2 Jun 2025
Viewed by 900
Abstract
Background/Objectives: To develop a nomogram for predicting tumor aggressiveness and the presence of lymphovascular space involvement (LVSI) in patients with endometrial cancer (EC) using preoperative MRI and pathology–laboratory data. Methods: This IRB-approved, retrospective, multicenter study included 245 patients with histologically confirmed EC who [...] Read more.
Background/Objectives: To develop a nomogram for predicting tumor aggressiveness and the presence of lymphovascular space involvement (LVSI) in patients with endometrial cancer (EC) using preoperative MRI and pathology–laboratory data. Methods: This IRB-approved, retrospective, multicenter study included 245 patients with histologically confirmed EC who underwent preoperative MRI and surgery at participating institutions between January 2020 and December 2024. Tumor type and grade, both from preoperative biopsy and surgical specimens, as well as preoperative CA125 and HE4 levels, were retrieved from institutional databases. A preoperative MRI was used to assess tumor morphology (polypoid vs. infiltrative), maximum diameter, presence and depth (< or >50%) of myometrial invasion, cervical stromal invasion (yes/no), and minimal tumor-to-serosa distance. The EC-to-uterus volume ratio was also calculated. Results: Among the 245 patients, 27% demonstrated substantial LVSI, and 35% were classified as aggressive on final histopathology. Multivariate analysis identified independent MRI predictors of LVSI, including cervical stromal invasion (OR = 9.06; p = 0.0002), tumor infiltration depth (OR = 2.09; p = 0.0391), and minimal tumor-to-serosa distance (OR = 0.81; p = 0.0028). The LVSI prediction model yielded an AUC of 0.834, with an overall accuracy of 78.4%, specificity of 92.2%, and sensitivity of 43.1%. For tumor aggressiveness prediction, significant predictors included biopsy grade (OR = 8.92; p < 0.0001), histological subtype (OR = 12.02; p = 0.0021), and MRI-detected serosal involvement (OR = 14.39; p = 0.0268). This model achieved an AUC of 0.932, with an accuracy of 87.0%, sensitivity of 79.8%, and specificity of 91.2%. Both models showed excellent calibration (Hosmer–Lemeshow p > 0.86). Conclusions: The integration of MRI-derived morphological and quantitative features with clinical and histopathological data allows for effective preoperative risk stratification in endometrial cancer. The two nomograms developed for predicting LVSI and tumor aggressiveness demonstrated high diagnostic performance and may support individualized surgical planning and decision-making regarding adjuvant therapy. These models are practical, reproducible, and easily applicable in standard clinical settings without the need for radiomics software, representing a step toward more personalized gynecologic oncology. Full article
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18 pages, 1666 KB  
Article
Multi-Steroid Profiling and Machine Learning Reveal Androgens as Candidate Biomarkers for Endometrial Cancer Diagnosis: A Case-Control Study
by Marija Gjorgoska, Angela E. Taylor, Špela Smrkolj and Tea Lanišnik Rižner
Cancers 2025, 17(10), 1679; https://doi.org/10.3390/cancers17101679 - 16 May 2025
Viewed by 1241
Abstract
Objective: To evaluate the diagnostic and prognostic potential of preoperative serum steroid levels in endometrial cancer (EC) alone and in combination with clinical parameters and biomarkers CA-125 and HE4. Methods: This single-center observational study included 62 patients with EC and 70 controls with [...] Read more.
Objective: To evaluate the diagnostic and prognostic potential of preoperative serum steroid levels in endometrial cancer (EC) alone and in combination with clinical parameters and biomarkers CA-125 and HE4. Methods: This single-center observational study included 62 patients with EC and 70 controls with benign uterine conditions who underwent surgery between June 2012 and February 2020. Preoperative serum levels of classic androgens, 11-oxyandrogens, glucocorticoids and mineralocorticoids were measured using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Machine learning was used to assess their diagnostic and prognostic value alone and combined with clinical parameters and tumor biomarkers. Results: Patients with EC had significantly higher serum levels of classic androgens (androstenedione, testosterone), 11-oxyandrogens (11β-hydroxy-androstenedione, 11β-hydroxy-testosterone) and glucocorticoids (17α-hydroxy-progesterone, 11-deoxycortisol) compared to controls. While individual steroids had limited diagnostic value, a multivariate model including classic androgens, CA-125, HE4, BMI and parity achieved an AUC 0.87, 79.1% sensitivity and 74.7% specificity in distinguishing EC from benign uterine condition. This model outperformed our previously published model based on CA-125, HE4 and BMI (AUC: 0.81, p < 0.0001). Prognostically, HE4 was the strongest marker for lymphovascular space invasion (LVSI) (AUC: 0.79) and deep myometrial invasion (MI) (AUC: 0.71). Among steroids, androstenedione was the most predictive of LVSI (AUC: 0.67), while 11β-hydroxy-testosterone was the strongest predictor of deep MI (AUC: 0.64). Conclusions: Patients with EC exhibit distinct steroid hormone profiles. While steroids alone offer modest diagnostic and prognostic value, integrating them into multivariate models improves diagnostic accuracy. Full article
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13 pages, 1768 KB  
Article
The Predictive Value of Preoperative Histological Risk Factors in Early Cervical Cancer
by Jana Adams, Amelie Wingels, Constanze Amir-Kabirian, Janice Katharina Jeschke, Lara Gesemann, Büsra Eser, Caroline Lenz, Bernd Morgenstern and Fabinshy Thangarajah
J. Clin. Med. 2025, 14(10), 3277; https://doi.org/10.3390/jcm14103277 - 8 May 2025
Viewed by 801
Abstract
Background: Cervical cancer is a leading cause of morbidity and mortality among women globally. Currently, treatment is primarily based on tumor staging; however, discrepancies between preoperative and postoperative tumor staging remain a significant challenge and may impact treatment decisions and outcomes. This [...] Read more.
Background: Cervical cancer is a leading cause of morbidity and mortality among women globally. Currently, treatment is primarily based on tumor staging; however, discrepancies between preoperative and postoperative tumor staging remain a significant challenge and may impact treatment decisions and outcomes. This study aims to investigate the disparity between preoperative and postoperative risk factors in early-stage cervical cancer, with a particular focus on the histopathological parameters and the correlation with preclinical risk factors. Methods: Patients who underwent surgical treatment for an initial diagnosis of primary cervical carcinoma at the University Hospital Cologne in the Department of Gynecology and Obstetrics between 2015 and 2021 were included. A retrospective analysis was conducted to examine variations in histological parameters and their relationships with preclinical risk factors, such as age, BMI, smoking status, and HPV status, along with pretherapeutic diagnostic results. Results: In 85.7% of cases, preoperative grading showed concordance with postoperative grading. Postoperative upgrading was observed in 14.3% of cases with no instances of downgrading. Inconsistent findings were noted for venous invasion (3.6% of cases) and lymphovascular space invasion (6.7% of cases). No significant correlations were found between pre- and postoperative discrepancies and preclinical risk factors or pretherapeutic diagnostics. Kaplan–Meier analyses revealed no impact of discordance in grading (p = 0.559) or lymphatic vessel invasion (p = 0.752) on recurrence-free survival. Conclusions: The analyzed discrepancies were not influenced by preclinical risk factors or pretherapeutic interventions and showed no significant prognostic relevance for the patients’ recurrence-free survival. More robust conclusions would require further studies with larger sample sizes. Full article
(This article belongs to the Section Oncology)
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12 pages, 244 KB  
Article
Microsatellite Instability as a Risk Factor for Occult Lymph Node Metastasis in Early-Stage Endometrial Cancer: A Retrospective Multicenter Study
by Carlo Ronsini, Stefano Restaino, Federico Paparcura, Giuseppe Vizzielli, Antonio Raffone, Mariano Catello Di Donna, Giuseppe Cucinella, Vito Chiantera and Pasquale De Franciscis
Cancers 2025, 17(7), 1162; https://doi.org/10.3390/cancers17071162 - 30 Mar 2025
Cited by 3 | Viewed by 2489
Abstract
Objectives: This study investigates the association between microsatellite instability (MSI) and the risk of occult lymph node metastases (LNMs) in patients with early-stage endometrial cancer (EC) who showed no evidence of nodal involvement on preoperative imaging. Methods: A retrospective multicenter cohort study was [...] Read more.
Objectives: This study investigates the association between microsatellite instability (MSI) and the risk of occult lymph node metastases (LNMs) in patients with early-stage endometrial cancer (EC) who showed no evidence of nodal involvement on preoperative imaging. Methods: A retrospective multicenter cohort study was conducted, including 237 patients with EC who underwent primary staging surgery between January 2022 and October 2024. The patients were stratified into two groups based on MSI status. The primary outcome was the prevalence of occult LNMs. Statistical analyses included univariate and multivariate logistic regression models, adjusting for potential confounders such as tumor grading and lymphovascular space invasion (LVSI). The significance of the models was assessed using the maximum likelihood method and Bayesian Information Criterion (BIC). Measures to reduce bias included blinding the data analyst, standardization of histopathological evaluation, and exclusion of patients with genetic conditions predisposing to MSI. Results: The MSI group had a significantly higher incidence of occult LNMs compared to the MSS group (19% vs. 6.7%, p = 0.005). The multivariate analysis confirmed MSI as an independent risk factor for LNMs (OR = 1.105, 95% CI 1.016–1.202, p = 0.020). The sub-analysis showed that loss of MLH1/PMS2 or both MLH1/PMS2 and MSH2/MSH6 heterodimers further increased LNMs risk, independently from other risk factors. Conclusions: MSI is independently associated with a higher risk of occult LNMs in early-stage EC, suggesting a potential role for MSI profiling in refining lymph node staging strategies. Future prospective studies should assess the prognostic impact of this association and its implications for surgical decision-making. Full article
(This article belongs to the Special Issue New Advances in the Diagnosis of Gynecological Cancer)
15 pages, 1017 KB  
Systematic Review
Clinicopathological Comparison Between GREB1- and ESR1-Rearranged Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Systematic Review
by Livia Maccio, Damiano Arciuolo, Angela Santoro, Antonio Raffone, Diego Raimondo, Susanna Ronchi, Nicoletta D’Alessandris, Giulia Scaglione, Michele Valente, Belen Padial Urtueta, Francesca Addante, Nadine Narducci, Emma Bragantini, Jvan Casarin, Giuseppe Angelico, Stefano La Rosa, Gian Franco Zannoni and Antonio Travaglino
Diagnostics 2025, 15(6), 792; https://doi.org/10.3390/diagnostics15060792 - 20 Mar 2025
Cited by 2 | Viewed by 914
Abstract
Introduction: Among uterine tumors resembling ovarian sex cord tumors (UTROSCTs), it has been suggested that GREB1-rearranged cases are biologically distinct from ESR1-rearranged cases and might be considered as a separate entity. Objectives: The aim of this systematic review was to assess [...] Read more.
Introduction: Among uterine tumors resembling ovarian sex cord tumors (UTROSCTs), it has been suggested that GREB1-rearranged cases are biologically distinct from ESR1-rearranged cases and might be considered as a separate entity. Objectives: The aim of this systematic review was to assess the difference between GREB1- and ESR1-rearranged UTROSCTs with regard to several clinico-pathological parameters. Methods: Three electronic databases were searched from their inception to February 2025 for all studies assessing the presence of GREB1 and ESR1 rearrangements in UTROSCTs. Exclusion criteria comprised overlapping patient data, case reports, and reviews. Statistical analysis was performed to compare clinicopathological variables between GREB1- and ESR1-rearranged UTROSCTs. Dichotomous variables were compared by using Fisher’s exact test; continuous variables were compared by using Student’s t-test. A p-value < 0.05 was considered significant. Results: Six studies with 88 molecularly classified UTROSCTs were included. A total of 36 cases were GREB1-rearranged, and 52 cases were ESR1-rearranged. GREB1-rearranged UTROSCTs showed a significantly older age (p < 0.001), larger tumor size (p = 0.002), less common submucosal/polypoid growth (p = 0.005), higher mitotic index (p = 0.010), more common LVSI (p = 0.049), and higher likelihood to undergo hysterectomy (p = 0.008) compared to ESR1-rearranged cases. No significant differences were detected with regard to margins, cytological atypia, necrosis, retiform pattern, and rhabdoid cells. No significant differences were found in the immunohistochemical expression of any of the assessed markers (wide-spectrum cytokeratins, α-inhibin, calretinin, WT1, CD10, CD56, CD99, smooth muscle actin, desmin, h-caldesmon, Melan-A/MART1, SF1, or Ki67). GREB1-rearranged UTROSCTs showed significantly lower disease-free survival compared to ESR1-rearranged UTROSTCs (p = 0.049). Conclusions: In conclusion, GREB1-rearranged UTROSCTs occur at an older age, are less likely to display a submucosal/polypoid growth, and exhibit larger size, a higher mitotic index, more common lymphovascular space invasion, and lower disease-free survival compared to ESR1-rearranged UTROSCTs. Nonetheless, the similar immunophenotype suggests that they belong to the same tumor family. Further studies are necessary to confirm this point. Full article
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13 pages, 968 KB  
Article
Sentinel Lymph Node Detection in Cervical Cancer: Challenges in Resource-Limited Settings with High Prevalence of Large Tumours
by Szilárd Leó Kiss, Mihai Stanca, Dan Mihai Căpîlna, Tudor Emil Căpîlna, Maria Pop-Suciu, Botond Istvan Kiss, Szilárd Leó Kiss and Mihai Emil Căpîlna
J. Clin. Med. 2025, 14(4), 1381; https://doi.org/10.3390/jcm14041381 - 19 Feb 2025
Cited by 1 | Viewed by 1815
Abstract
Background/Objectives: Cervical cancer primarily disseminates through the lymphatic system, with the metastatic involvement of pelvic and para-aortic lymph nodes significantly impacting prognosis and treatment decisions. Sentinel lymph node (SLN) mapping is critical in guiding surgical management. However, resource-limited settings often lack advanced [...] Read more.
Background/Objectives: Cervical cancer primarily disseminates through the lymphatic system, with the metastatic involvement of pelvic and para-aortic lymph nodes significantly impacting prognosis and treatment decisions. Sentinel lymph node (SLN) mapping is critical in guiding surgical management. However, resource-limited settings often lack advanced detection tools like indocyanine green (ICG). This study evaluated the feasibility and effectiveness of SLN biopsy using alternative techniques in a high-risk population with a high prevalence of large tumours. Methods: This prospective, observational study included 42 patients with FIGO 2018 stage IA1–IIA1 cervical cancer treated between November 2019 and April 2024. SLN mapping was performed using methylene blue alone or combined with a technetium-99m radiotracer. Detection rates, sensitivity, and false-negative rates were analysed. Additional endpoints included tracer technique comparisons, SLN localization patterns, and factors influencing detection success. Results: SLNs were identified in 78.6% of cases, with bilateral detection in 57.1%. The combined technique yielded higher detection rates (93.3% overall, 80% bilateral) compared to methylene blue alone (70.4% overall, 40.7% bilateral, p < 0.05). The sensitivity and negative predictive values were 70% and 93.87%, respectively. Larger tumours (>4 cm), deep stromal invasion, and prior conization negatively impacted detection rates. False-negative SLNs were associated with larger tumours and positive lymphovascular space invasion. Conclusions: SLN biopsy is feasible in resource-limited settings, with improved detection rates using combined tracer techniques. However, sensitivity remains suboptimal due to a steep learning curve and challenges in high-risk patients. Until a high detection accuracy is achieved, SLN mapping should complement, rather than replace, pelvic lymphadenectomy in high-risk cases. Full article
(This article belongs to the Special Issue Laparoscopy and Surgery in Gynecologic Oncology)
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