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10 pages, 559 KB  
Article
Factors Associated with Para-Aortic Lymph Node Metastasis in High-Risk Endometrial Cancer
by Fatma Ceren Güner, Elif Iltar, Müge Ateş Tıkız, Selen Doğan, Nasuh Utku Doğan, Hasan Aykut Tuncer and Tayup Şimşek
Medicina 2025, 61(12), 2189; https://doi.org/10.3390/medicina61122189 - 10 Dec 2025
Viewed by 147
Abstract
Background and Objectives: Para-aortic lymph node involvement is a key prognostic factor in high-risk endometrial cancer. This study aimed to identify factors associated with para-aortic lymph node metastasis and to assess their predictive value for surgical decision-making. Materials and Methods: A [...] Read more.
Background and Objectives: Para-aortic lymph node involvement is a key prognostic factor in high-risk endometrial cancer. This study aimed to identify factors associated with para-aortic lymph node metastasis and to assess their predictive value for surgical decision-making. Materials and Methods: A retrospective analysis was conducted on 81 patients with high-risk endometrial cancer who underwent systematic pelvic and para-aortic lymphadenectomy between January 2015 and December 2024. Factors evaluated included histologic subtype, lymphovascular space invasion (LVSI), cervical stromal involvement, depth of myometrial invasion, and tumor diameter. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of para-aortic metastasis. Receiver operating characteristic (ROC) analysis was used to determine the optimal tumor size threshold. Results: Para-aortic lymph node metastasis was identified in 21.0% of patients, and isolated para-aortic metastasis was observed in 2.5%. In univariate analysis, pelvic lymph node positivity, LVSI, cervical stromal invasion, deep myometrial invasion, and tumor size ≥ 3.55 cm were significantly associated with para-aortic spread. Multivariate analysis revealed that pelvic lymph node positivity was the only independent predictor (OR 39.0; 95% CI 5.06–301.46; p < 0.001). Conclusions: Pelvic lymph node status serves as a strong and independent predictor of para-aortic metastasis in high-risk endometrial cancer. A tumor diameter greater than 3.5 cm may also indicate an increased risk of para-aortic spread. These findings suggest that selective and individualized para-aortic assessment strategies may be considered to improve staging accuracy and optimize surgical planning in this patient population. Full article
(This article belongs to the Section Oncology)
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33 pages, 1320 KB  
Review
Fueling the Seed: Growth Factors and Cytokines Driving Cancer Stem Cells in Gynecological Malignancies
by Alessandro Sarcinella, Juan Sebastian Guerra Villacis and Maria Felice Brizzi
Int. J. Mol. Sci. 2025, 26(23), 11462; https://doi.org/10.3390/ijms262311462 - 26 Nov 2025
Viewed by 460
Abstract
Gynecological cancers remain a major global health burden due to their high incidence, molecular heterogeneity, and frequent resistance to conventional therapies. Beyond well-established genetic alterations and targeted treatments, growing attention has been directed toward the role of cancer stem cells (CSCs), a rare [...] Read more.
Gynecological cancers remain a major global health burden due to their high incidence, molecular heterogeneity, and frequent resistance to conventional therapies. Beyond well-established genetic alterations and targeted treatments, growing attention has been directed toward the role of cancer stem cells (CSCs), a rare tumor subpopulation with self-renewal, differentiation, and tumor-initiating capacities. CSCs are sustained by a specialized microenvironment, the cancer stem cell niche, where growth factors, cytokines, hypoxia, and stromal interactions converge to promote stemness, chemoresistance, and metastatic potential. In breast cancer, signaling axes such as EGFR, IGF, TGFβ, and HGF/c-Met critically regulate CSC expansion, particularly in aggressive subtypes like triple-negative tumors. In ovarian cancer, factors including HGF, VEGFA, IGF, and stromal-derived BMPs drive CSC plasticity and contribute to relapse after platinum therapy. Endometrial CSCs are supported by pathways involving TGFβ, BMP2, and Netrin-4/c-Myc signaling, while in cervical cancer, VEGF, IGF-1, Gremlin-1, and TGFβ-mediated circuits enhance stem-like phenotypes and drug resistance. Cytokine-driven inflammation, especially via IL-3, IL-6, IL-8, IL-10, and CCL5, further fosters CSC survival and immune evasion across gynecologic malignancies. Preclinical studies demonstrate that targeting growth factors and cytokine signaling, through monoclonal antibodies, receptor inhibitors, small molecules, or cytokine modulation, can reduce CSC frequency, restore chemosensitivity, and enhance immunotherapy efficacy. This review highlights the interplay between CSCs, growth factors, and cytokines as central to tumor progression and relapses, emphasizing their translational potential as therapeutic targets in precision oncology for gynecological cancers. Full article
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15 pages, 2964 KB  
Article
Interplay Between Immune Microenvironment CD8+ Tumor-Infiltrating Lymphocytes and PDL-1 Expression as Prognostic Markers in Invasive Cervical Squamous Cell Carcinoma
by Laura-Andra Petrică, Mariana Deacu, Georgeta Camelia Cozaru, Anca Florentina Mitroi, Gabriela Izabela Bălţătescu, Manuela Enciu, Oana Cojocaru, Anca-Antonela Nicolau, Andrei Radu Baz, Lucian Șerbănescu and Mariana Aşchie
Medicina 2025, 61(11), 2007; https://doi.org/10.3390/medicina61112007 - 10 Nov 2025
Viewed by 415
Abstract
Background: Cervical cancer remains a major cause of cancer-related morbidity and mortality worldwide, with limited therapeutic options for advanced disease. As we better understand the fine mechanisms involved in the interaction between tumor cells and the tumor microenvironment, new paths and opportunities [...] Read more.
Background: Cervical cancer remains a major cause of cancer-related morbidity and mortality worldwide, with limited therapeutic options for advanced disease. As we better understand the fine mechanisms involved in the interaction between tumor cells and the tumor microenvironment, new paths and opportunities will emerge. Recent evidence highlights the prognostic and predictive roles of immune checkpoint markers and tumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, in shaping treatment outcomes. Objectives: This study investigated the immunohistochemical expression of PD-L1 and CD8+ TILs in 48 newly diagnosed, treatment-naive cervical cancer cases and analyzed their associations with clinicopathological features and survival outcomes. Results: In our cohort, we observed that PD-L1 positivity was identified in 68.8% of cases, most frequently in advanced FIGO stages and in tumors with lympho-vascular invasion or with a high proliferation rate evaluated by the Ki-67 index. High levels of intra-tumoral CD8+ TILs were observed in 52.1% of cases and correlated positively with stromal TILs, lower proliferation rates, and absence of vascular invasion. A significant inverse relationship was found between PD-L1 expression and the density of CD8+ TILs (p = 0.047). Survival analysis showed that patients exhibiting a “cold” immunophenotype with low levels of CD8+ TILs and PD-L1-positive tumors had worse outcomes, while high levels of CD8+ TILs played a protective role. Conclusions: Our study highlights the importance of the immunohistochemical assessment of PD-L1 and CD8+ TILs biomarkers, which have a complementary inter-relationship and have a significant prognostic impact on cervical squamous cell carcinoma. PD-L1 positivity marks aggressive disease features, while higher intra-tumoral CD8+ TIL density is protective. Their combined evaluation may improve patient stratification and inform immunotherapy strategies. Full article
(This article belongs to the Section Obstetrics and Gynecology)
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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 751
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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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
Cited by 3 | Viewed by 1039
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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16 pages, 1931 KB  
Article
Single Cell RNA Sequencing of Papillary Cancer Mesenchymal Stem/Stromal Cells Reveals a Transcriptional Profile That Supports a Role for These Cells in Cancer Progression
by Danny Jandu, Nani Latar, Artida Bajrami, Rachel Queen, Megan Hasoon, Matthew Teasdale, Rafiqul Hussain, Jonathan Coxhead, Sebastian Aspinall and Annette Meeson
Int. J. Mol. Sci. 2025, 26(10), 4957; https://doi.org/10.3390/ijms26104957 - 21 May 2025
Viewed by 1492
Abstract
Papillary thyroid cancer (PTC) contains mesenchymal stem/stromal cells (MSCs), but their contribution to PTC progression is not clear. In this study, we compared the transcriptional signatures of normal thyroid (NT) and PTC-derived MSCs with the aim of determining if these have distinct transcriptomes [...] Read more.
Papillary thyroid cancer (PTC) contains mesenchymal stem/stromal cells (MSCs), but their contribution to PTC progression is not clear. In this study, we compared the transcriptional signatures of normal thyroid (NT) and PTC-derived MSCs with the aim of determining if these have distinct transcriptomes that might influence PTC progression. We used flow cytometry in combination with a panel of MSC clusters of differentiation (CD) markers and showed that both thyroid MSC populations expressed MSC markers and lacked expression of markers not normally expressed by MSCs. In addition, we determined that both MSC populations could differentiate to adipocytes and osteocytes. Analysis of single cell RNA sequencing data from both MSC populations revealed, regardless of tissue of origin, that both contained similar numbers of subpopulations. Cluster analysis revealed similarity in expression of both MSC populations for stromal markers, the vascular marker VEGFA and the smooth muscle marker CALD1, while smaller subpopulations expressed markers of more lineage-committed thyroid cells. PTC MSCs also showed upregulated expression of 28 genes, many of which are known to be involved in epithelial–mesenchymal transition (EMT) and/or disease progression in several types of cancers, including but not limited to breast cancer, gastric cancer, cervical carcinoma, bladder cancer and thyroid cancer. This included several members of the S100 and IGFBP gene families. Taken together, these data support a role for PTC MSCs in PTC progression. 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 2 | Viewed by 2072
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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14 pages, 772 KB  
Article
Uterine Carcinosarcoma—A Retrospective Cohort Analysis from a Tertiary Centre on Epidemiology, Management Approach, Outcomes and Survival Patterns
by Sarah Louise Smyth, Katherine Ripullone, Andreas Zouridis, Christina Pappa, Geraldine Spain, Aikaterina Gkorila, Amika McCulloch, Phoebe Tupper, Farhat Bibi, Negin Sadeghi, Alisha Sattar, Shmaila Siddiki, Susan Addley, Mostafa Abdalla, Federico Ferrari, Stephen Damato, Sean Kehoe and Hooman Soleymani majd
Cancers 2025, 17(4), 635; https://doi.org/10.3390/cancers17040635 - 14 Feb 2025
Cited by 3 | Viewed by 1915
Abstract
Background/Objectives: Uterine carcinosarcoma (UCS) refers to a rare high-grade aggressive epithelial non-endometrioid endometrial carcinoma, with tumour cells demonstrating epithelial–mesenchymal metaplastic transition and composed of both carcinomatous epithelial and sarcomatous (homologous or heterologous) components. Methods: The aim of this study was to evaluate the [...] Read more.
Background/Objectives: Uterine carcinosarcoma (UCS) refers to a rare high-grade aggressive epithelial non-endometrioid endometrial carcinoma, with tumour cells demonstrating epithelial–mesenchymal metaplastic transition and composed of both carcinomatous epithelial and sarcomatous (homologous or heterologous) components. Methods: The aim of this study was to evaluate the epidemiology, management approach, outcomes and survival patterns of patients with UCS. Seventy-seven cases of UCS treated with primary surgery in a single tertiary centre underwent retrospective cohort analysis across a ten-year period. Observational data on clinicopathological variables and treatment pathways were reviewed and independent risk factors for relapse and mortality were analysed. Results: The 5-year disease-free and overall survival rates were 52.10% and 46.6%, respectively. Cervical stromal involvement was independently related to disease-free survival (HR = 6.26; 95%CI 1.82–21.59; p = 0.004) and overall survival (HR = 3.64; 95%CI 1.42–9.38; p = 0.007), whilst sarcomatous component type was independently related to recurrence only (HR = 3.62; 95%CI 1.38–9.51; p = 0.009) after adjusting for other pathological and treatment variables. No significant difference in recurrence or mortality was found when comparing the performance of pelvic lymph node dissection (p = 0.803 and p = 0.192 respectively) or the administration of adjuvant treatment (p = 0.546 and p = 0.627 respectively). Conclusions: Whilst our data suggests an encouraging similarity in overall survival rates compared with the literature, UCS continues to represent significant treatment challenges—with a paucity of guidelines available. Data regarding molecular analysis was not systemically available in our cohort, the more recent introduction of which (alongside the revision of endometrial cancer staging) will undoubtedly provide UCS patients with improved therapeutic options in the future. Full article
(This article belongs to the Special Issue Lymph Node Dissection for Gynecologic Cancers)
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10 pages, 464 KB  
Article
Challenging the Binary Classification of Endometrioid Endometrial Adenocarcinoma: The Evaluation of Grade 2 as an Independent Entity Based on Prognostic Characteristics and Recurrence Patterns
by Andreas Zouridis, Ammara Kashif, Ahmed Darwish, Christina Pappa, Federico Ferrari, Sarah Louise Smyth, Negin Sadeghi, Alisha Sattar, Stephen Damato, Mostafa Abdalla, Sean Kehoe, Susan Addley and Hooman Soleymani Majd
Cancers 2025, 17(1), 127; https://doi.org/10.3390/cancers17010127 - 3 Jan 2025
Cited by 1 | Viewed by 1754
Abstract
Background: Although grade is a well-recognised prognostic factor for endometrioid endometrial cancer (EEC), in more studies grade 1 (G1) and grade 2 (G2) EEC are combined and compared together with grade 3 (G3) tumours. The aim of our study is to separately investigate [...] Read more.
Background: Although grade is a well-recognised prognostic factor for endometrioid endometrial cancer (EEC), in more studies grade 1 (G1) and grade 2 (G2) EEC are combined and compared together with grade 3 (G3) tumours. The aim of our study is to separately investigate the outcomes, prognostic factors and recurrence patterns of G2 EEC and whether the differentiation between G1 and G2 EEC is clinically useful. Methods: we retrospectively reviewed 523 patients with EEC treated with primary surgery over a decade (March 2010–January 2020) at Oxford University Hospitals NHS Trust, focusing on those with G2 disease. Results: Patients with G2 EEC had worse 5-year cancer-specific survival (93.3% vs. 98.5%, p < 0.01) compared to patients with G1 EEC, but a favourable prognosis compared to G3 EEG, both in terms of disease-free survival (91.6 vs. 83.8%, p = 0.04) and cancer-specific survival (93.3% vs. 78.5%, p < 0.01). Both stage and grade are independent risk factors for cancer-specific mortality in EEC. Cervical stromal involvement, parametrial involvement and distant metastatic disease are all independent risk factors for cancer-related mortality in G2 ECC. Only 12.5% of recurrences of G2 EEC were diagnosed with examination in routine follow up in asymptomatic patients. Conclusions: our results suggest that the grading system should continue to differentiate G1 EEC and G2 EEC for better prognosis interpretation. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Clinical and Translational Research)
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11 pages, 2070 KB  
Article
Analysis of Clinicopathological and Molecular Features of Microcystic, Elongated, and Fragmented Pattern Invasion in Endometrioid Endometrial Cancer
by Xiaobo Zhang, Bo Han and Danhua Shen
Cancers 2024, 16(20), 3555; https://doi.org/10.3390/cancers16203555 - 21 Oct 2024
Cited by 1 | Viewed by 2093
Abstract
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 [...] Read more.
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. Full article
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37 pages, 3379 KB  
Article
The Polish Society of Gynecological Oncology Guidelines for the Diagnosis and Treatment of Cervical Cancer (v2024.0)
by Jacek J. Sznurkowski, Lubomir Bodnar, Łukasz Szylberg, Agnieszka Zołciak-Siwinska, Anna Dańska-Bidzińska, Dagmara Klasa-Mazurkiewicz, Agnieszka Rychlik, Artur Kowalik, Joanna Streb, Mariusz Bidziński and Włodzimierz Sawicki
J. Clin. Med. 2024, 13(15), 4351; https://doi.org/10.3390/jcm13154351 - 25 Jul 2024
Cited by 3 | Viewed by 8166
Abstract
Background: Recent publications underscore the need for updated recommendations addressing less radical surgery for <2 cm tumors, induction chemotherapy, or immunotherapy for locally advanced stages of cervical cancer, as well as for the systemic therapy for recurrent or metastatic cervical cancer. Aim [...] Read more.
Background: Recent publications underscore the need for updated recommendations addressing less radical surgery for <2 cm tumors, induction chemotherapy, or immunotherapy for locally advanced stages of cervical cancer, as well as for the systemic therapy for recurrent or metastatic cervical cancer. Aim: To summarize the current evidence for the diagnosis, treatment, and follow-up of cervical cancer and provide evidence-based clinical practice recommendations. Methods: Developed according to AGREE II standards, the guidelines classify scientific evidence based on the Agency for Health Technology Assessment and Tariff System criteria. Recommendations are graded by evidence strength and consensus level from the development group. Key Results: (1) Early-Stage Cancer: Stromal invasion and lymphovascular space involvement (LVSI) from pretreatment biopsy identify candidates for surgery, particularly for simple hysterectomy. (2) Surgical Approach: Minimally invasive surgery is not recommended, except for T1A, LVSI-negative tumors, due to a reduction in life expectancy. (3) Locally Advanced Cancer: concurrent chemoradiation (CCRT) followed by brachytherapy (BRT) is the cornerstone treatment. Low-risk patients (fewer than two metastatic nodes or FIGO IB2-II) may consider induction chemotherapy (ICT) followed by CCRT and BRT after 7 days. High-risk patients (two or more metastatic nodes or FIGO IIIA, IIIB, and IVA) benefit from pembrolizumab with CCRT and maintenance therapy. (4) Metastatic, Persistent, and Recurrent Cancer: A PD-L1 status from pretreatment biopsy identifies candidates for Pembrolizumab with available systemic treatment, while triplet therapy (Atezolizumab/Bevacizumab/chemotherapy) becomes a PD-L1-independent option. Conclusions: These evidence-based guidelines aim to improve clinical outcomes through precise treatment strategies based on individual risk factors, predictors, and disease stages. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Diagnosis, Targeted Therapies, and Management)
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12 pages, 1332 KB  
Systematic Review
Systematic Review—Role of MRI in Cervical Cancer Staging
by Jason Chen, Yu Xuan Kitzing and Glen Lo
Cancers 2024, 16(11), 1983; https://doi.org/10.3390/cancers16111983 - 23 May 2024
Cited by 8 | Viewed by 4301
Abstract
A systematic review of the diagnostic accuracy of MRI in the staging of cervical cancer was conducted based on the literature from the last 5 years. A literature search was performed in the Cochrane Library, EMBASE, MEDLINE and PubMed databases using the MeSH [...] Read more.
A systematic review of the diagnostic accuracy of MRI in the staging of cervical cancer was conducted based on the literature from the last 5 years. A literature search was performed in the Cochrane Library, EMBASE, MEDLINE and PubMed databases using the MeSH terms “cervical cancer”, “MRI” and “neoplasm staging”. A total of 110 studies were identified, of which 8 fit the inclusion criteria. MRI showed adequate accuracy (74–95%) and high sensitivity (92–100%) in assessing stromal invasion. The data for MRI in terms of assessing vaginal and pelvic side wall involvement were wide ranging and inconclusive. In assessing lymph node metastasis, MRI showed an adequate accuracy (73–90%), specificity (75–91%) and NPV (71–96%) but poor sensitivity (52–75%) and PPV (52–75%). MRI showed high accuracy (95%), sensitivity (78–96%), specificity (87–94%), and NPV (98–100%) but poor PPV (27–42%) in detecting bladder involvement. There was a paucity of data on the use of MRI in assessing rectal involvement in cervical cancer. Overall, the literature was heterogenous in the definitions and language used, which reduced the comparability between articles. More research is required into the diagnostic accuracy of MRI in the staging of cervical cancer and there must be increased consistency in the definitions and language used in the literature. Full article
(This article belongs to the Section Methods and Technologies Development)
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17 pages, 3320 KB  
Article
The Impact of Patient Characteristics, Risk Factors, and Surgical Intervention on Survival in a Cohort of Patients Undergoing Neoadjuvant Treatment for Cervical Cancer
by Irinel-Gabriel Dicu-Andreescu, Marian-Augustin Marincaș, Virgiliu-Mihail Prunoiu, Ioana Dicu-Andreescu, Sînziana-Octavia Ionescu, Anca-Angela Simionescu, Eugen Brătucu and Laurențiu Simion
Medicina 2023, 59(12), 2147; https://doi.org/10.3390/medicina59122147 - 11 Dec 2023
Cited by 3 | Viewed by 2492
Abstract
Introduction: Cervical cancer is among the most frequent types of neoplasia worldwide and remains the fourth leading cause of cancer death in women, a fact that raises the necessity for further development of therapeutic strategies. NCCN guidelines recommend radiation therapy with or [...] Read more.
Introduction: Cervical cancer is among the most frequent types of neoplasia worldwide and remains the fourth leading cause of cancer death in women, a fact that raises the necessity for further development of therapeutic strategies. NCCN guidelines recommend radiation therapy with or without chemotherapy as the gold standard for locally advanced cervical cancer. Also, some studies claim that performing surgery after chemo-radiation therapy does not necessarily improve the therapeutic outcome. This study aims to determine the impact of the risk factors, various characteristics, and surgical treatment for patients in different stages of the disease on survival rate. Material and methods: Our study started as a retrospective, observational, unicentric one, carried out on a cohort of 96 patients diagnosed with cervical cancer from the surgical department of the Bucharest Oncological Institute, followed from 1 January 2019 for a period of 3 years. After the registration of the initial parameters, however, the study became prospective, as the patients were closely monitored through periodical check-ups. The end-point of the study is either the death of the participants or reaching the end of the follow-up period, and, therefore, we divided the cohort into two subgroups: the ones who survived after three years and the ones who did not. All 96 patients, with disease stages ranging from IA2 to IIIB, underwent radio-chemotherapy followed by adjuvant surgery. Results: Among the 96 patients, 45 (46%) presented residual tumor after radio-chemotherapy. Five patients (5%) presented positive resection margins at the post-operative histopathological examination. The presence of residual tumor, the FIGO stage post-radiotherapy, positive resection margins, and lympho-vascular and stromal invasions differed significantly between the subgroups, being more represented in the subgroup that reached the end-point. Variables correlated with the worst survival in Kaplan–Meier were the pelvic lymph node involvement—50% at three years (p—0.015)—and the positive resection margins—only 20% at three years (p < 0.001). The univariate Cox model identified as mortality-associated risk factors the same parameters as above, but also the intraoperative stage III FIGO (p < 0.001; HR 9.412; CI: 2.713 to 32.648) and the presence of post-radiotherapy adenopathy (p—0.031; HR: 3.915; CI: 1.136 to 13.487) identified through imagistic methods. The independent predictors of the overall survival rate identified were the positive resection margins (p—0.002; HR: 6.646; CI 2.0 to 22.084) and the post-radiotherapy stage III FIGO (p—0.003; HR: 13.886; CI: 2.456 to 78.506). Conclusions: The most important predictor factors of survival rate are the positive resection margins and the FIGO stage after radiotherapy. According to the NCCN guidelines in stages considered advanced (beyond stages IB3, IIA2), the standard treatment is neoadjuvant chemoradiotherapy. In our study, with radical surgery after neoadjuvant therapy, 46% of patients presented residual tumor at the intraoperative histopathological examination, a fact that makes the surgical intervention an important step in completing the treatment of these patients. In addition, based on the patient’s features/comorbidities and the clinical response to chemotherapy/radiotherapy, surgeons could carefully tailor the extent of radical surgery, thus resulting in a personalized surgical approach for each patient. However, a potential limitation can be represented by the relatively small number of patients (96) and the unicentric nature of our study. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Cervical Cancer)
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12 pages, 1236 KB  
Article
The Prognostic Characteristics and Recurrence Patterns of High Grade Endometrioid Endometrial Cancer: A Large Retrospective Analysis of a Tertiary Center
by Andreas Zouridis, Kianoush Zarrindej, Joshua Rencher, Christina Pappa, Ammara Kashif, Sarah Louise Smyth, Negin Sadeghi, Alisha Sattar, Stephen Damato, Federico Ferrari, Antonio Simone Laganà, Mostafa Abdalla, Sean Kehoe, Susan Addley and Hooman Soleymani majd
J. Clin. Med. 2023, 12(9), 3141; https://doi.org/10.3390/jcm12093141 - 26 Apr 2023
Cited by 6 | Viewed by 3606
Abstract
High grade endometrioid endometrial cancer (HGEEC) is a heterogeneous group of tumors with unclear prognostic features. The aim of the present study is to evaluate the independent risk factors for recurrence and mortality and to describe the recurrence patterns of HGEEC. Ninety-six consecutive [...] Read more.
High grade endometrioid endometrial cancer (HGEEC) is a heterogeneous group of tumors with unclear prognostic features. The aim of the present study is to evaluate the independent risk factors for recurrence and mortality and to describe the recurrence patterns of HGEEC. Ninety-six consecutive cases of HGEEC treated with primary surgery in a single Tertiary Center were retrospectively reviewed. Clinicopathological and treatment details were recorded, and all patients were closely followed up. Disease-free, overall and cancer-specific survival rates were 83.8%, 77.8% and 83.6%, respectively. Cervical stromal involvement was independently related to recurrence (HR = 25.67; 95%CI 2.95–223.30; p = 0.003) and cancer-related death (HR = 15.39; 95%CI 1.29–183.43; p = 0.031) after adjusting for other pathological and treatment variables. Recurrence rate was 16%, with 60% of these cases having lung metastases and only one case with single vaginal vault recurrence. 81.81% of the recurrences presented with symptoms and not a single recurrence was diagnosed in routine follow-up clinical examination. In conclusion, the recurrence pattern may suggest that patient-initiated follow-up (PIFU) could be considered a potential alternative to clinical-based follow-up for HGEEC survivors, especially for patients without cervical involvement and after two years from treatment. Additional caution is needed in patients with cervical stromal involvement. Full article
(This article belongs to the Section Oncology)
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13 pages, 4132 KB  
Article
Infiltration by Intratumor and Stromal CD8 and CD68 in Cervical Cancer
by Polina Dimitrova, Mariela Vasileva-Slaveva, Velizar Shivarov, Ihsan Hasan and Angel Yordanov
Medicina 2023, 59(4), 728; https://doi.org/10.3390/medicina59040728 - 7 Apr 2023
Cited by 3 | Viewed by 3163
Abstract
Background and Objectives: The tumor microenvironment (TME) plays a major role in neoplastic development. Various types of cells can be found in the TME. These cells can be classified into two groups, immunosuppressive and immunostimulatory types, depending on the function they perform in [...] Read more.
Background and Objectives: The tumor microenvironment (TME) plays a major role in neoplastic development. Various types of cells can be found in the TME. These cells can be classified into two groups, immunosuppressive and immunostimulatory types, depending on the function they perform in the antitumor immune response (IR). By interacting both with each other and with tumor cells, different immune mechanisms are activated or inhibited, which can suppress or promote the development and progression of cervical cancer (CC). Our aim was to investigate some of the main components of the cellular immune response in TME—tumor-infiltrating cytotoxic T cells (Tc, CD8+) and tumor-associated macrophages (TAMs, CD68+)—in patients with CC. Materials and Methods: We analyzed 72 paraffin-embedded tumor tissues of patients diagnosed and treated at Medical University Pleven, Bulgaria. Patients were classified according to the 2018 FIGO (International Federation of Gynaecology and Obstetrics) classification. From each patient, we selected one histological slide with hematoxylin eosin staining. In a microscopic evaluation, CD8+ T lymphocytes and CD68+-positive macrophages were counted in the tumor and stroma of five randomly selected fields at ×40 magnification (HPF). We analyzed the relationship between intratumoral and stromal CD8 and CD68 expression and FIGO stage and N status. Results: There was no significant association between the expression levels of intratumoral and stromal CD68+ cells in the different FIGO stages and according to the lymph nodes’ involvement. For CD8+ cells, the association of stromal infiltration was also not found, but T intratumor infiltration was associated with a higher FIGO stage, despite the fact that the results did not reach significance (p = 0.063, Fisher test). Intratumoral CD8+ cells were significantly associated with positive N status, (p = 0.035). Discussion: The separation of tumor-infiltrating cytotoxic T cells and tumor-associated macrophages into intratumoral and stromal is inconsequential. In our study, the level of infiltration of CD68+ cells in tumors and stromata was not significantly associated with tumor progression or lymph node involvement. The results were different for CD8+ cells, in which levels of infiltration were associated with lymph nodes’ statuses. Conclusions: The separate evaluation of CD68+ immune cells in the TME as intratumoral and stromal is not beneficial for defining prognoses, since the presence of these cells is not associated with the patient’s stage. In our study, the presence of CD8+ cells was significantly associated with lymph node metastases. The prognostic value of the obtained results can be enriched with an additional study of the lymphocyte phenotype, including B and other subtypes of T lymphocytes, NK cells, as well as molecules involved in the immune response, such as HLA subtypes. Full article
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