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17 pages, 730 KB  
Review
The Evolving Role of Radiation Oncology in the Management of Uterine Cervical Carcinoma: A State-of-the-Art Review for Non-Radiation Oncologists
by Christian Haydeé Flores-Balcázar, Shuhey Augusto Matsumoto-Palomares, Diego Iván Chávez-Zaldívar, Adamary Itai Marin-Trinidad, Francisco Gerardo Castro-Pérez and Lucely del Carmen Cetina-Pérez
Life 2025, 15(12), 1883; https://doi.org/10.3390/life15121883 - 10 Dec 2025
Viewed by 38
Abstract
Cervical cancer is one of the most common gynecological tumors globally. When diagnosed, treatment decisions should be based on a risk–benefit analysis of each treatment modality to obtain a cure with minimum complications. The optimal approach for management should consider clinical factors such [...] Read more.
Cervical cancer is one of the most common gynecological tumors globally. When diagnosed, treatment decisions should be based on a risk–benefit analysis of each treatment modality to obtain a cure with minimum complications. The optimal approach for management should consider clinical factors such as age, menopausal status, medical comorbidities, histological type, tumor size, and the extent of disease. Radiotherapy is the cornerstone for successful management in almost all clinical stages of this disease. Options for primary treatment in patients with early cervical cancer may include radical hysterectomy, fertility-sparing surgery, and postoperative radiotherapy with or without platinum-based chemotherapy (CT) according to pathology specimen findings. For locally advanced cervical cancer, chemoradiotherapy has been the standard of care based on the results of clinical trials that showed an overall survival (OS) advantage when adding cisplatin to radiotherapy. After chemoradiotherapy, a cervical boost is mandatory for increased local control and better survival. For metastatic or recurrent cervical cancer, the treatment approach is tailored according to symptoms and performance status. As many techniques and new technologies are available to decrease toxicity while improving the therapeutic ratio, it becomes necessary to collate the current evidence that most effectively enables clinicians to make informed decisions in the management of cervical cancer patients. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Recent Advances and Future Perspectives)
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15 pages, 7486 KB  
Article
Diagnostic Value and Interobserver Reproducibility of Histopathological Features in Fumarate Hydratase-Deficient Uterine Leiomyomas
by Aleksandra Rogozhina, Alina Badlaeva, Anna Tregubova, Aleksandra Asaturova, Maria Kuznetsova and Gennady Sukhikh
Diagnostics 2025, 15(23), 3006; https://doi.org/10.3390/diagnostics15233006 - 26 Nov 2025
Viewed by 293
Abstract
Background/Objectives: Fumarate hydratase-deficient leiomyomas (dFH-LMs) are a rare subtype of uterine smooth muscle tumors (USMTs) with implications for hereditary leiomatosis and renal cell carcinoma (HLRCC). Although several morphologic clues have been proposed, their diagnostic reproducibility is poorly defined. We aimed to determine the [...] Read more.
Background/Objectives: Fumarate hydratase-deficient leiomyomas (dFH-LMs) are a rare subtype of uterine smooth muscle tumors (USMTs) with implications for hereditary leiomatosis and renal cell carcinoma (HLRCC). Although several morphologic clues have been proposed, their diagnostic reproducibility is poorly defined. We aimed to determine the diagnostic significance of histopathologic features associated with fumarase deficiency and the reproducibility of key morphologic criteria for defining dFH-LMs. Methods: A retrospective analysis was performed on 45 USMTs that were initially classified as atypical leiomyomas (ALMs). The cohort comprised patients aged 21 to 75 years who had surgery at one tertiary medical care center from 2016 to 2025. Hematoxylin–eosin (H&E) slides were independently examined by three pathologists for features associated with FH deficiency, including eosinophilic globules, staghorn-like vessels, diffuse nuclear atypia, “bizarre” nuclei, and prominent nucleoli with halos. Molecular status was determined by immunohistochemistry (IHC) for fumarate hydratase (FH) and S-(2-succino)-cysteine (2SC). Interobserver agreement was quantified using Fleiss’s κ and Cohen’s κ. Results: Loss of FH expression was detected in 26/45 tumors (57.7%). Eosinophilic globules occurred in 88.5% of dFH-LMs, but only in 15.8% of ALMs (p < 0.001). By majority consensus (≥2 of 3 reviewers), the eosinophilic globules predicted FH deficiency with a sensitivity of 88.0% and a specificity of 85.0%; interobserver reproducibility was substantial (κ = 0.63). Staghorn-like vessels occurred in 73.1% of dFH-LMs vs. 26.3% of ALMs (p = 0.02) and diffuse nuclear atypia (84.6%) was also more frequent in dFH-LMs (p = 0.01). Patients with dFH-LMs were significantly younger than those with ALMs (Median, 34 vs. 41 years). Conclusions: Eosinophilic globules, staghorn-like vessels and diffuse nuclear atypia have been shown to have high diagnostic value and could be considered morphologic indicators of dFH-LMs. The substantial interobserver reproducibility of eosinophilic globules makes this feature particularly promising for routine clinical practice. Full article
(This article belongs to the Special Issue Pathology and Diagnosis of Gynecologic Diseases, 3rd Edition)
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13 pages, 1720 KB  
Case Report
Clinically Advanced Warty Invasive Squamous Cell Carcinoma of the Cervix with p16 Overexpression—Case Study and Literature Review
by Laura-Andra Petrică, Mariana Deacu, Georgeta Camelia Cozaru, Gabriela Izabela Bălţătescu and Mariana Aşchie
Reports 2025, 8(4), 243; https://doi.org/10.3390/reports8040243 - 21 Nov 2025
Viewed by 389
Abstract
Background and Clinical Significance: Warty (condylomatous) squamous cell carcinoma (SCC) of the uterine cervix is a rare papillary variant of SCC, usually associated with good prognosis. Case Presentation: We report the clinical case of a postmenopausal woman with vaginal bleeding, anemia, and an [...] Read more.
Background and Clinical Significance: Warty (condylomatous) squamous cell carcinoma (SCC) of the uterine cervix is a rare papillary variant of SCC, usually associated with good prognosis. Case Presentation: We report the clinical case of a postmenopausal woman with vaginal bleeding, anemia, and an enlarged, exophytic tumor mass protruding from the cervix. MRI showed a solid–necrotic cervical–uterine mass with invasion of bladder, rectum, both parametria, and the left ureter, with regional lymphadenopathy and FIGO IVA stage was established. Biopsies from the cervical tumor revealed invasive, well-differentiated SCC with conspicuous koilocytic atypia in superficial and deep nests, consistent with warty (condylomatous) SCC. Immunohistochemistry showed p16 overexpression, an intermediate nuclear proliferation rate, and a non-mutational pattern for p53 immunostaining. Radiotherapy was recommended but the patient’s condition deteriorated rapidly and she died three months after initial diagnosis. Due to the rarity of this type of tumor, we conducted a search on PubMed, Scopus, and Web of Science from inception to 31 July 2025 and we identified ten reports available for evaluation. A total of 32 cases were identified, usually with FIGO stage I or II, mostly with low-risk HPV infection and with good prognosis. Conclusions: The advanced stage and limited tolerance for therapy in this case emphasize the importance of HPV vaccination and HPV-based screening to prevent late, non-curable presentations. Accurate distinction from condyloma acuminatum and verrucous or papillary SCC is clinically relevant because management and outcomes differ. Since some of the cases reported in the literature had a worse clinical course, with shorter disease-free survival and overall survival, including our case, further research is mandatory in the future to unravel those features which might predict a poor outcome. Full article
(This article belongs to the Section Obstetrics/Gynaecology)
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26 pages, 6735 KB  
Article
The Emerging Role of FAM171A2 in Gynecological Malignancies: Bioinformatic Insights from UCEC and Ovarian Cancer
by Sibel Soylemez and Durmus Ayan
Int. J. Mol. Sci. 2025, 26(22), 11126; https://doi.org/10.3390/ijms262211126 - 18 Nov 2025
Viewed by 482
Abstract
The FAM171A2 gene encodes a transmembrane protein that is not well characterized but is implicated in signaling, vesicle trafficking, and interactions with the extracellular matrix. Its specific role in gynecologic malignancies has yet to be defined. To our knowledge, this is the first [...] Read more.
The FAM171A2 gene encodes a transmembrane protein that is not well characterized but is implicated in signaling, vesicle trafficking, and interactions with the extracellular matrix. Its specific role in gynecologic malignancies has yet to be defined. To our knowledge, this is the first systematic study to comprehensively assess FAM171A2 expression, clinical relevance, and molecular network interactions in gynecologic malignancies. We employed an integrative approach utilizing multi-platform transcriptomic and proteomic resources—GEPIA2, TNMplot, TIMER2, UALCAN, KM-plotter, Human Protein Atlas (HPA), Gene Expression Omnibus (GEO), STRING, TargetScan, and ENCORI—to comprehensively profile FAM171A2 expression, its clinicopathologic correlations, survival associations, predicted interaction networks, and post-transcriptional regulation in ovarian cancer (OV) and uterine corpus endometrial carcinoma (UCEC). Immunohistochemical analysis from the HPA indicated low or undetectable levels of the FAM171A2 protein in OV and UCEC. In contrast, RNA sequencing analyses demonstrated upregulated mRNA expression in OV and a modest, non-significant increase in UCEC compared to normal tissues. Pan-cancer screening using TNMplot and TIMER2 revealed elevated expression in gynecologic tumors relative to most other cancer types. In OV, UALCAN analysis identified associations with demographic and molecular characteristics, such as increased expression in TP53-mutant tumors, while trends related to stage and grade were minimal. Similarly, stratifications in UCEC suggested modulation by race, body mass index (BMI), and menopausal status rather than stage. Survival analyses using KM-plotter showed no significant association with overall survival in either type of cancer. TargetScan predicted 211 microRNAs potentially targeting FAM171A2, and ENCORI correlations supported tumor-type-specific post-transcriptional regulation: in OV, negative correlations were observed with miR-15b-5p, miR-16-5p, and miR-497-5p, along with long non-coding RNA (lncRNA) effects, including positive correlations with BACE1-AS and negative correlations with PVT1 and UCA1. In UCEC, significant negative correlations were found with LINC00582, LINC-ROR, MEG3, NEAT1, and SNHG12. STRING network analysis suggested two modules associated with FAM171A2: a neuronal/synaptic cluster, exemplified by NPTX1, and an immune/transcriptional cluster, exemplified by ZNF696. Validation using the GEO showed mixed results: two UCEC datasets were non-significant, whereas one OV cohort (GSE36368) exhibited higher tumor expression. FAM171A2 demonstrates context-dependent expressions that are modulated post-transcriptionally in gynecologic cancers. While it is not independently prognostic, it may serve as a molecular hub at the intersection of neuronal and immune pathways, warranting further mechanistic investigations and exploration as a panel-based biomarker. Full article
(This article belongs to the Special Issue Gynecologic Oncology: Molecular Mechanisms and Therapies)
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10 pages, 2314 KB  
Case Report
Mesonephric Hyperplasia and Adenocarcinoma of the Cervix: A Rare Evolution, Case Report, and Review of the Literature
by Angel Yordanov, Diana Strateva, Albena Baicheva, Ivan Baichev, Stoyan Kostov and Vasilena Dimitrova
Reports 2025, 8(4), 230; https://doi.org/10.3390/reports8040230 - 11 Nov 2025
Viewed by 458
Abstract
Background and Clinical Significance: Mesonephric adenocarcinoma (MA) of the uterine cervix is an exceptionally uncommon and aggressive cancer that arises from remnants of the mesonephric duct. It was first classified by the World Health Organization (WHO) in the 2020 WHO Classification of [...] Read more.
Background and Clinical Significance: Mesonephric adenocarcinoma (MA) of the uterine cervix is an exceptionally uncommon and aggressive cancer that arises from remnants of the mesonephric duct. It was first classified by the World Health Organization (WHO) in the 2020 WHO Classification of Female Genital Tumors as a type of cervical adenocarcinoma, also referred to as Gartner’s duct carcinoma. Due to its rarity, both detection and treatment pose significant challenges, and there is little information on its clinical manifestations and prognosis. Mesonephric hyperplasia (MH) in the uterine cervix is an uncommon condition that is often misdiagnosed as adenocarcinoma. Case Presentation: We present the case of a 49-year-old, asymptomatic, perimenopausal woman diagnosed with cervical mesonephric adenocarcinoma following a routine Pap smear, performed by Papanicolaou test, with a III A-B result; however, a cone biopsy revealed stage IB1 mesonephric adenocarcinoma. The patient underwent a radical hysterectomy type C (Querleu–Morrow 2017 classification). The final pathology confirmed stage IB2 of the cancer (2018 classification) according to The International Federation of Gynecology and Obstetrics (FIGO), with previous evidence of mesonephric hyperplasia from a trial abrasion performed three years earlier. Conclusions: This case highlights the challenges in recognizing and managing mesonephric hyperplasia and adenocarcinoma of the cervix. Given the uncommon nature of this cancer, clinicians should consider it when treating patients with ambiguous cervical pathology and mesonephric hyperplasia. Optimizing patient outcomes relies on early detection, accurate staging, and radical surgical treatment. Full article
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18 pages, 677 KB  
Article
Sarcopenic Obesity and Sarcopenic Visceral Obesity, Calculated Using the Skeletal Muscle İndex and Visceral Fat İndex at the L3 Vertebra Level, Do Not Predict Survival Rates in Endometrial Cancer Patients
by Melek Özdemir, Gamze Gököz Doğu, Burcu Yapar Taşköylü, Muhammet Arslan, Burak Kurnaz, Atike Gökçen Demiray, Arzu Yaren, Serkan Değirmencioğlu and Yeliz Arman Karakaya
J. Clin. Med. 2025, 14(22), 7915; https://doi.org/10.3390/jcm14227915 - 7 Nov 2025
Viewed by 536
Abstract
Objective: Obesity increases the risk of endometrial cancer (EC). In this study, we aimed to investigate the prognostic effect of sarcopenia, sarcopenic obesity and sarcopenic visceral obesity, calculated with the help of cross-sectional imaging methods of muscle and visceral adipose tissue from [...] Read more.
Objective: Obesity increases the risk of endometrial cancer (EC). In this study, we aimed to investigate the prognostic effect of sarcopenia, sarcopenic obesity and sarcopenic visceral obesity, calculated with the help of cross-sectional imaging methods of muscle and visceral adipose tissue from body composition parameters, in EC. Methods: Patients diagnosed with EC were identified between January 2014 and June 2024. The combination of radiological markers and patient outcomes can predict prognosis. The skeletal muscle index (SMI) and visceral fat index (VFI) were calculated from computed tomography (CT) and/or abdominal magnetic resonance (MR) scans taken at the time of diagnosis at the Lumbal 3 (L3) vertebra level. The findings of these analyses demonstrate the strongest correlation with the ratio of muscle and visceral fat tissue throughout the body. The loss of muscle and fat is an unfavourable indicator in patients with EC. The present study analysed the prognostic values of sarcopenia, sarcopenic obesity, sarcopenic visceral obesity, and the visceral fat index in EC. The total skeletal muscle area was calculated in square centimetres. Body surface area (m2) was calculated using the Mosteller formula: ((height (cm) × weight (kg))/3600)1/2. To normalize body composition components, the skeletal muscle index was calculated as cm2/m2. Results: The study comprised a total of 236 EC patients. The prevalence of sarcopenia, sarcopenic obesity, and sarcopenic visceral obesity were found to be 48.31%, 33.47%, and 22.88%, respectively. The presence of sarcopenia, high VFI levels, sarcopenic obesity, and sarcopenic visceral obesity did not demonstrate statistical significance in the survival analysis. However, stage increase (p = 0.001), primary tumour localization in the lower uterine segment (p = 0.001), serous carcinoma (p = 0.001), increased grade in endometrioid carcinoma (p = 0.023), and lymphovascular invasion (p = 0.001) were significantly associated with increased mortality risk. The presence of sarcopenia was found to be significant in patients with obesity (p = 0.008) and those aged ≥ 65 years (p = 0.001). Conclusions: In EC survival, established prognostic factors such as serous histopathology, LVI positivity, and the extent of surgical staging are prioritised. The presence of these well-established markers means the potential effect of BMI-based observations, such as the ‘obesity paradox’, and even body composition measurements, such as sarcopenic obesity, are now statistically insignificant. Our findings suggest that aggressive tumour biology (serous type, LVI) and surgery, rather than metabolic variables such as sarcopenia, sarcopenic obesity and sarcopenic visceral obesity, are the direct reason for the survival difference. This is due to the tumour’s aggressive nature and clinical characteristics (e.g., age at diagnosis, operability, stage, primary tumour localization in the lower uterine segment, serous carcinoma, grade, and LVI positivity) rather than metabolic variables. Full article
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15 pages, 7681 KB  
Case Report
Multinodular Hydropic Leiomyoma in a 41-Year-Old Patient: A Case Report
by Diana Xie Freire, Alissia Blumer, Teresa Teixeira da Silva, Sonali Düblin, Joachim Diebold and Ivo Fähnle-Schiegg
J. Clin. Med. 2025, 14(21), 7615; https://doi.org/10.3390/jcm14217615 - 27 Oct 2025
Viewed by 442
Abstract
Uterine leiomyomas are a heterogenous group of benign mesenchymal tumours. While diagnosis is usually achieved through clinical assessment and pelvic ultrasound (PU), atypical subtypes are not as easily recognisable and can be mistaken for malignant tumours such as leiomyosarcoma or ovarian carcinoma. We [...] Read more.
Uterine leiomyomas are a heterogenous group of benign mesenchymal tumours. While diagnosis is usually achieved through clinical assessment and pelvic ultrasound (PU), atypical subtypes are not as easily recognisable and can be mistaken for malignant tumours such as leiomyosarcoma or ovarian carcinoma. We describe the case of a 41-year-old patient who presented with increasing bulk symptoms, urinary frequency and growth of a hydropic leiomyoma (HLM) of the left lateral and posterior uterine wall that had been known for 10 years, confirmed with previous biopsy. The tumour filled the entire pelvic cavity in PU and was increasingly difficult to delineate; therefore an abdominal hysterectomy without oophorectomy was performed. Gross tissue examination showed an irregularly enlarged, asymmetric uterus with an intrauterine subserosal mass and an extrauterine papillary tumour arising from the right and posterior uterine wall. The tumour measured 20 × 17 × 10 cm in size. Numerous smooth muscle nodules were observed within the uterus and extending into the extrauterine component in a continuous transition, exhibiting a benign, bland appearance. The nodules were separated by abundant edematous connective tissue with increased vascularization. Histopathological analysis revealed low mitotic activity with no evidence of nuclear atypia, pleomorphism, or necrosis. Immunohistochemical staining confirmed the diagnosis of a benign smooth muscle tumour. Our findings confirm a rare, benign smooth muscle neoplasm with both intrauterine and extrauterine involvement, and add to the existing literature regarding presentation, diagnostic and therapeutic challenges associated with HLM. Full article
(This article belongs to the Section Oncology)
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16 pages, 739 KB  
Article
Endometrial Carcinoma and Associated Secondary Neoplasia: The Role of Clinical Features, Pathology, and Comorbidities in a University-Affiliated Clinical Center from Western Romania
by Ioana Hurmuz, Robert Barna, Bianca Natarâș, Iuliana-Anamaria Trăilă, Denisa Anderco, Sorin Dema, Aura Jurescu, Dorela-Codruța Lăzureanu, Sorina Tăban and Alis Dema
Medicina 2025, 61(10), 1748; https://doi.org/10.3390/medicina61101748 - 25 Sep 2025
Cited by 1 | Viewed by 495
Abstract
Background and Objectives: Multiple primary malignancies involving endometrial carcinoma (EC) present complex diagnostic and management challenges. This study aimed to identify clinical, pathological, and demographic patterns among patients with EC and a second primary tumor and assess the role of comorbidities in [...] Read more.
Background and Objectives: Multiple primary malignancies involving endometrial carcinoma (EC) present complex diagnostic and management challenges. This study aimed to identify clinical, pathological, and demographic patterns among patients with EC and a second primary tumor and assess the role of comorbidities in tumor behavior. Materials and Methods: We retrospectively analyzed 35 women diagnosed with EC and a second malignancy between 2017 and 2024. We evaluated clinical variables, tumor characteristics, and comorbidities. Statistical analysis included chi-square tests, Mann–Whitney U tests, Kruskal–Wallis tests, Spearman correlations, and logistic regression. Multiple testing correction was applied using the Benjamini–Hochberg method. Results: Endometrioid EC was the most prevalent subtype (80%), most frequently associated with breast (28.5%) and colorectal cancers (11.4%). Obesity (45.7%), hypertension (62.9%), and diabetes (22.9%) were common. While univariate analysis suggested associations between comorbidities and tumor features (e.g., obesity and tumor type, ρ = 0.30, p = 0.08), no correlation remained significant after adjustment. Logistic regression identified age (OR = 0.88, CI: 0.79–0.98, p = 0.022) and obesity (OR = 0.11, CI: 0.01–0.83, p = 0.033) as independent predictors of non-endometrioid histology. Conclusions: These findings suggest that age and obesity may influence histological differentiation in EC with multiple primaries. This study suggest that age and obesity may play a role in the histological differentiation of EC in patients with multiple primary tumors. The small cohort size (n = 35) limits the statistical power and generalizability of the results; therefore, they should be regarded as exploratory and hypothesis-generating, warranting validation in larger prospective studies. Full article
(This article belongs to the Section Obstetrics and Gynecology)
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15 pages, 2948 KB  
Article
Pan-Cancer Analysis of Mutations Affecting Protein Liquid–Liquid Phase Separation Revealing Clinical Implications
by Xiaoping Cen, Lulu Wang, Kai Yu, Huanming Yang, Roland Eils, Wei Dong, Huan Lin and Zexian Liu
Biology 2025, 14(10), 1320; https://doi.org/10.3390/biology14101320 - 25 Sep 2025
Viewed by 974
Abstract
Phase separation is one of the mechanisms critical for protein function, and its aberrances are associated with cancer development. However, mutations that affect protein phase separation and cancer development have not been systematically identified and analyzed. In this study, we systematically identified the [...] Read more.
Phase separation is one of the mechanisms critical for protein function, and its aberrances are associated with cancer development. However, mutations that affect protein phase separation and cancer development have not been systematically identified and analyzed. In this study, we systematically identified the mutations affecting protein liquid–liquid phase separation in multiple cancers. We calculated the phase separation scores alterations for over 1,200,000 mutations across 16 cancer types using the TCGA dataset. We then performed pathway enrichment, kinase, TF enrichment, and survival analysis to identify related biological processes and clinical implications. Nearly 10% of the mutations were defined to affect phase separation in pan-cancer. These mutations occupied a consistent percentage in each cancer type. Extremely influencing mutations accumulate on stomach adenocarcinoma (STAD), uterine corpus endometrial carcinoma (UCEC), and skin cutaneous melanoma (SKCM). Moreover, proteins carrying these mutations are enriched in cancer-related pathways, including TGF-beta signaling pathways and polycomb repressive complex. Phase separation of these proteins would be regulated by kinases, including CDK1, CDK2, and EGFR, and transcription factors, including ZNF407, ZNF318, and MGA proteins, to play functions in cancer. Protein–Protein Interaction Network revealed that these phase separation proteins are highly interconnected. Finally, patients carrying mutations that positively affect the protein phase separation are associated with poor prognosis in skin cutaneous melanoma (SKCM) and lung squamous cell carcinoma (LUSC), which could be partially explained by the pathogenicity of these mutations. The study provided a pan-cancer landscape for depicting the association of phase separation and cancer mutations, which would be a rich data resource for understanding the association of cancer mutations and phase separation. Full article
(This article belongs to the Section Bioinformatics)
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14 pages, 3389 KB  
Article
PET/CT Imaging Characteristics of Gastric-Type Endocervical Adenocarcinoma: Findings from a Small Exploratory Series
by Yun Wang, Xuan Zhou, Yun Xi, Hanmei Lou, Linfa Li, Heqing Yi and Tao Zhu
Curr. Oncol. 2025, 32(10), 530; https://doi.org/10.3390/curroncol32100530 - 23 Sep 2025
Viewed by 796
Abstract
Objective: To identify distinctive 18F-FDG positron emission tomography (PET)/computer tomography (CT) features of gastric-type endocervical adenocarcinoma (GAS) that differentiate it from squamous cell carcinoma (SCC) and usual-type endocervical adenocarcinoma (UEA), as well as to correlate these findings with pathological characteristics. Methods: Patients treated [...] Read more.
Objective: To identify distinctive 18F-FDG positron emission tomography (PET)/computer tomography (CT) features of gastric-type endocervical adenocarcinoma (GAS) that differentiate it from squamous cell carcinoma (SCC) and usual-type endocervical adenocarcinoma (UEA), as well as to correlate these findings with pathological characteristics. Methods: Patients treated between December 2018 and December 2024 were retrospectively reviewed. The study included 12 GAS, 48 SCC, and 30 UEA cases. Evaluated parameters included tumor morphology, cystic components, uterine cavity fluid, N/M staging, tumor diameter, the cervical lesion maximum standardized uptake value (SUVmax), and the tumor-to-liver maximum standardized uptake ratio (T/L SUVmax). Results: GAS predominantly exhibited diffuse infiltrative growth (11/12), in contrast to mass-like growth observed in SCC (37/48) and UEA (24/30) (both p < 0.001). Cystic components, uterine cavity fluid, and peritoneal metastasis occurred significantly more frequently in GAS (12/12, 11/12, 5/12, respectively) compared to SCC and UEA (all p < 0.001). Elevated CA19-9 levels were more common in GAS (9/12) compared with SCC (p < 0.001). Tumor diameter did not differ significantly among the groups (p > 0.05). SUVmax and T/L SUVmax values were significantly lower in GAS (7.5 ± 3.8 and 2.5 ± 1.6, respectively) than in UEA (19.1 ± 11.4 and 5.7 ± 3.4) and SCC (17.4 ± 6.7 and 5.5 ± 2.6) (all p < 0.001). Conclusion: The clinical characteristics of GAS include infiltrative tumor growth, fluid accumulation in the uterine cavity, frequent formation of microcystic or macrocystic components, peritoneal metastasis, and elevated CA19-9 levels. In this cohort, SUVmax and T/L SUVmax values in GAS were significantly lower than those observed in SCC and UEA. Full article
(This article belongs to the Section Gynecologic Oncology)
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40 pages, 17153 KB  
Review
Immunotherapy of Oncovirus-Induced Cancers: A Review on the Development and Efficacy of Targeted Vaccines
by Chi Sing Ng
Vaccines 2025, 13(9), 911; https://doi.org/10.3390/vaccines13090911 - 27 Aug 2025
Viewed by 1874
Abstract
Background: A number of viruses are oncogenic. These include the human papilloma virus (HPV), Epstein–Barr virus (EBV), Kaposi sarcoma human herpes virus 2/human herpes virus 8 (KSHHV/HHV8), hepatitis B virus, (HBV), hepatitis C virus (HCV), Merkel cell polyoma virus (McPyV), and the human [...] Read more.
Background: A number of viruses are oncogenic. These include the human papilloma virus (HPV), Epstein–Barr virus (EBV), Kaposi sarcoma human herpes virus 2/human herpes virus 8 (KSHHV/HHV8), hepatitis B virus, (HBV), hepatitis C virus (HCV), Merkel cell polyoma virus (McPyV), and the human T-cell leukemia virus type 1 (HTLV-1). These viruses cause malignancies ranging from carcinomas, sarcomas, lymphomas, to leukemias. This review aims to study the effects and efficacy of vaccines against these viruses and the cancers they cause in their prevention and treatment. Methods: The literature in the past 30 years was searched employing Scopus and Google Scholar using the keywords “oncogenic viruses, HPV, EBV, KSHHV, HHV8, Polyoma virus, HTLV-1, COVID-19, carcinoma, sarcoma, lymphoma, leukemia, anti-virus vaccines”. Results: Prophylactic vaccines against the HPV and HBV are highly effective in preventing and reducing the incidence of uterine cervical and hepatocellular carcinomas. Prophylactic vaccines against other oncogenic viruses have been less successful, though efficacious in some experimental animals. Therapeutic vaccines are still mostly under evaluation and development. Conclusions: Identification of oncogenic viruses has rendered anti-viral vaccines conspicuous tools for preventing and treating cancers they cause. Many endeavors for the development of such vaccines have been met with limited success, apart from the very effective anti-HPV and anti-HBV vaccines in universal vaccination programs. With the development of new vaccine technologies, it is hoped that effective vaccines against other oncogenic viruses will be developed in the future. Full article
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17 pages, 588 KB  
Article
Serum Levels of CA125 and HE4 as a Tool for Predicting Regional Lymph Node Metastatic Involvement in Endometrial Carcinoma
by Tomáš Crha, Petra Ovesná, Vít Weinberger, Michal Felsinger, Branislav Babjak, Dalibor Valík, Jitka Hausnerová and Luboš Minář
Cancers 2025, 17(17), 2740; https://doi.org/10.3390/cancers17172740 - 23 Aug 2025
Viewed by 1040
Abstract
Background: Endometrial carcinoma is the most common gynaecological malignant tumour in developed countries. At present, no routinely used serum biomarker is available for the prediction of lymph node metastasis (LNM). This study thus evaluates the potential of tumour markers CA125 and HE4 [...] Read more.
Background: Endometrial carcinoma is the most common gynaecological malignant tumour in developed countries. At present, no routinely used serum biomarker is available for the prediction of lymph node metastasis (LNM). This study thus evaluates the potential of tumour markers CA125 and HE4 as LNM predictors in endometrial carcinoma patients. Objectives: The aim of this study was to evaluate the potential use of CA125 and HE4 and to assess the viability of a model developed using the parameters of serum tumour marker levels for LNM risk stratification. Methods: A retrospective, single-institution study of 220 patients with biopsy-proven endometrial carcinoma was conducted from May 2020 to December 2023. Preoperative serum levels of HE4 and CA125 were determined. All patients underwent surgical lymph node staging. The study evaluated the sensitivity and specificity of tumour markers and of the developed LNM risk prediction model. Results: No LNM was observed in 167 of the 220 patients (75.9%), micrometastatic lymph node involvement was observed in 13 patients (5.9%), and macrometastatic involvement was observed in 24 patients (10.9%). Median CA125 and HE4 levels were significantly higher in patients with LNM than in those without. With a CA125 cut-off value of 35 IU/mL, a sensitivity of 70% and a specificity of 92% were obtained, while an HE4 cut-off value of 103 pmol/L yielded a sensitivity of 78% and a specificity of 80%. A prediction model combining CA125, HE4, and the extent of uterine invasion, as detected by ultrasound, yielded a sensitivity of 84% and a specificity of 98% in predicting LNM. Conclusions: CA125 and HE4, along with the prediction model, facilitate endometrial carcinoma patient subdivision into low- and high-risk LNM groups. As this method is technically simple, non-invasive, and inexpensive, it could be of undeniable benefit in the risk stratification of patients with multiple comorbidities, which limit the duration and extent of surgery. Full article
(This article belongs to the Special Issue Lymph Node Detection in Gynecological Cancers)
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20 pages, 744 KB  
Review
HER2/neu as a Signaling and Therapeutic Marker in Uterine Serous Carcinoma
by Victoria M. Ettorre, Luca Palmieri, Valentino Clemente and Alessandro D. Santin
Cells 2025, 14(16), 1282; https://doi.org/10.3390/cells14161282 - 19 Aug 2025
Viewed by 1954
Abstract
Research into aggressive gynecologic cancers such as uterine serous carcinoma (USC) has recently evolved from chemotherapy to the development of drugs targeting specific biomarkers differentially expressed/active in tumor cells. One such target is HER2/neu, which plays an important role in the coordination of [...] Read more.
Research into aggressive gynecologic cancers such as uterine serous carcinoma (USC) has recently evolved from chemotherapy to the development of drugs targeting specific biomarkers differentially expressed/active in tumor cells. One such target is HER2/neu, which plays an important role in the coordination of cell growth and differentiation. Importantly, when overexpressed and/or amplified in tumor cells, the downstream tyrosine kinase of HER2/neu becomes constitutively activated, causing dysregulated gene transcription. In breast cancer patients, HER2/neu has been successfully utilized for many years as a target for multiple monoclonal antibodies and more recently antibody–drug conjugates (ADCs). Use in gynecologic malignancies has been slower, however, due to recently identified unique characteristics of HER2/neu protein expression and gene amplification in biologically aggressive tumors such as USC including its major heterogeneity and lack of apical staining when compared to breast cancer. Accordingly, the use of optimal testing algorithms for HER2/neu status in patients with USC may have important implications for the development of novel, effective, and targeted treatment modalities against this lethal variant of endometrial cancer. In this review, we discuss HER2/neu gene expression in USC, evaluate the efficacy of HER2/neu-directed therapies in both preclinical and clinical settings, and discuss possible mechanisms of resistance to HER2/neu targeting agents. Full article
(This article belongs to the Special Issue Signaling Pathways in Endometrial Cancer Cells)
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21 pages, 3228 KB  
Article
CUSP06, a Novel CDH6-Targeted Antibody-Drug Conjugate, Demonstrates Antitumor Efficacy in Multiple CDH6-Expressing Human Cancer Models
by Wei Lu, Jing Shi, Wentao Zhang, Nicole Covino, Amy Penticoff, Robert Phillips, John Cogswell, Laurie Tatalick, Stephanie Pasas-Farmer, Jianjian Zhang, Caiwei Chen, Yixuan Wang, Huiyan Shi, Shuhui Liu, Xun Meng and Eric Slosberg
Pharmaceutics 2025, 17(8), 1049; https://doi.org/10.3390/pharmaceutics17081049 - 13 Aug 2025
Viewed by 2338
Abstract
Background/Objectives: Cadherin-6 (CDH6), also known as K-cadherin, is a type II classic cadherin molecule that plays an important role in the embryonic development of the kidney but has very limited expression in adult tissues. It is overexpressed in several human malignancies, primarily in [...] Read more.
Background/Objectives: Cadherin-6 (CDH6), also known as K-cadherin, is a type II classic cadherin molecule that plays an important role in the embryonic development of the kidney but has very limited expression in adult tissues. It is overexpressed in several human malignancies, primarily in ovarian cancer, renal cell carcinoma, as well as, less frequently, cholangiocarcinoma, uterine serous carcinoma, glioma, lung, pancreatic and thyroid cancers. The characteristic of limited expression in normal tissues, high expression in tumor tissues, and rapid internalization upon antibody binding makes CDH6 a well-suited antibody-drug conjugate (ADC) target. Methods: We developed a novel CDH6-targeting ADC, CUSP06, consisting of a proprietary humanized antibody selective for CDH6, a protease cleavable linker, and an exatecan payload, with a drug-to-antibody ratio (DAR) of 8. We further characterized the pharmacological activities of CUSP06 in multiple in vitro and in vivo models. Results: CUSP06 was selectively bound to cell surface CDH6 and was efficiently internalized into CDH6-positive ovarian cancer cells, and led to the induction of DNA damage and apoptosis of CDH6-positive cancer cells. CUSP06 exhibited strong antiproliferative activity against several CDH6-positive cancer cell lines and demonstrated strong bystander cell killing effect in the cell mixing experiments in vitro. CUSP06 exhibits excellent in vivo antitumor efficacy in CDH6-high or -low cell line-derived xenograft (CDX) or patient-derived xenograft (PDX) models from human ovarian, renal and uterine cancers, as well as cholangiocarcinoma. CUSP06 demonstrated a favorable safety profile in GLP-compliant toxicology studies in Sprague Dawley rats and cynomolgus monkeys. Conclusions: The preclinical data highlighted the therapeutic potential of CUSP06 in multiple CDH6-positive human cancers. Full article
(This article belongs to the Special Issue Advancements and Innovations in Antibody Drug Conjugates)
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17 pages, 2950 KB  
Case Report
Primary Invasive Vaginal Carcinoma Associated with Complete Utero-Vaginal Prolapse: A Case Report and Literature Review
by Maciej Korniluk, Weronika Niemyjska-Dmoch, Beata Gil-Sobocińska, Joanna Kabat, Lubomir Bodnar and Grzegorz Szewczyk
J. Clin. Med. 2025, 14(13), 4622; https://doi.org/10.3390/jcm14134622 - 30 Jun 2025
Viewed by 1366
Abstract
Background: Primary vaginal cancer is a rare gynecological condition. We present a case of complete utero-vaginal prolapse complicated by primary invasive vaginal carcinoma. To our knowledge, only a few similar cases have been reported in our region. Case Report: A 77-year-old woman, gravida [...] Read more.
Background: Primary vaginal cancer is a rare gynecological condition. We present a case of complete utero-vaginal prolapse complicated by primary invasive vaginal carcinoma. To our knowledge, only a few similar cases have been reported in our region. Case Report: A 77-year-old woman, gravida two and para two, was admitted for treatment of pelvic organ prolapse. The patient reported an eight-year history of uterine bulging but had not used a pessary. The gynecological examination revealed a complete manually irreducible utero-vaginal prolapse with an ulcerative lesion on the right posterolateral vaginal wall. The histological examination diagnosed an HPV-independent keratinizing squamous cell carcinoma, grade I. Comprehensive imaging showed no evidence of metastasis. The patient underwent radical hysterectomy, bilateral adnexectomy, complete resection of the vaginal mass, and pelvic lymphadenectomy. The histopathological examination confirmed clear surgical margins. According to the International Federation of Gynecology and Obstetrics (FIGO) staging system, the disease was classified as stage I vaginal cancer. Postoperatively, the patient received radiotherapy (45 Gy) and high-dose-rate brachytherapy (14 Gy). Conclusions: The co-occurrence of vaginal cancer and utero-vaginal prolapse is exceedingly rare. Surgical intervention followed by radiotherapy is the most common treatment approach. Given the aggressive nature of the disease, comprehensive follow-up is essential. Further research is needed to determine whether long-term genital prolapse increases the risk of vaginal carcinoma. Full article
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