Search Results (5,122)

Germline Whole-Exome Sequencing (WES) has emerged as a powerful genomic approach for investigating Hereditary Cancer predisposition through the comprehensive analysis of coding regions across the genome. Although multigene panels currently represent the standard diagnostic approach for Hereditary Cancer assessment, a substantial proportion of high-risk individuals and families remain molecularly unexplained. In this setting, germline WES may serve as a valuable second-tier strategy by identifying pathogenic variants in genes not routinely included in conventional testing panels and by addressing part of the unresolved “missing heritability” observed across Hereditary Cancer syndromes. Increasing evidence supports its application in hereditary breast and ovarian cancer, Lynch-like syndrome, colorectal polyposis, hereditary diffuse gastric cancer, and ovarian cancer predisposition, where WES has contributed to the identification of additional susceptibility genes and improved molecular characterization. Beyond Hereditary Cancer diagnostics, exome-based approaches have also been explored for tumour profiling, homologous recombination deficiency (HRD) assessment, biomarker discovery, and therapeutic stratification. However, despite its significant potential, the clinical implementation of WES remains challenging because of the high burden of variants of uncertain significance (VUS), difficulties in variant interpretation, incidental findings, and the need for robust functional validation of candidate genes. This review critically examines the current evidence supporting the clinical utility of germline WES in Hereditary Cancer syndromes, focusing on the clinical scenarios in which WES may provide meaningful additional information beyond multigene panels, its diagnostic yield, limitations, and future perspectives in precision oncology. Full article

Background: Ovarian cancer is frequently diagnosed at an advanced stage and remains one of the most lethal gynecologic malignancies. The development of multidrug resistance (MDR) during repeated chemotherapy is a major cause of treatment failure and is often associated with increased drug efflux mediated by transporters such as P-glycoprotein (P-gp). In this study, D-α-tocopheryl polyethylene glycol succinate (TPGS) and Soluplus^® (SOL) mixed micelles, abbreviated as TS, were developed to co-deliver apatinib (APA), a VEGFR-2 inhibitor, and etoposide (ETP), a topoisomerase II inhibitor, for MDR ovarian cancer models. The formulation was designed to improve the aqueous dispersion, cellular accumulation, and antitumor activity of APA and ETP. Methods: APA/ETP-loaded TS micelles (APA/ETP-mTS) were prepared and characterized in terms of particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), storage stability, and in vitro drug release. Anticancer efficacy was assessed using MTT assays, cellular uptake assays, and 3D tumor spheroid studies employing HeyA8-MDR cells, followed by in vivo toxicity and antitumor efficacy studies. Micellar formulations were denoted using the cargo–carrier format, where APA/ETP indicates co-loaded APA and ETP, C6 indicates coumarin-6 (C6) used as a fluorescent probe, mTS indicates TPGS/SOL mixed micelles, and mSOL indicates SOL-only micelles. Results: The selected APA/ETP-mTS formulation showed a particle size of 20.0 ± 5.1 nm, a PDI of 0.16 ± 0.05, near-neutral zeta potential, and encapsulation efficiencies exceeding 60% for both drugs. The micelles maintained colloidal stability at 4 °C for 4 weeks, although partial decreases in encapsulation efficiency were observed. Compared with APA/ETP solution, APA/ETP-mTS delayed the release of both drugs. C6-mTS showed higher intracellular fluorescence intensity than C6-mSOL, suggesting enhanced cellular accumulation associated with TPGS incorporation. APA/ETP-mTS showed greater cytotoxicity than free drugs in HeyA8-MDR monolayer cells and produced the strongest spheroid growth inhibition among the tested micellar formulations. In the HeyA8-MDR xenograft model, APA/ETP-mTS suppressed tumor growth and resulted in the lowest final tumor weight without apparent overt toxicity based on body weight and survival observations. Conclusions: These results suggest that APA/ETP-mTS is a promising micellar co-delivery platform for hydrophobic anticancer drugs in MDR ovarian cancer. Full article

(1) Background/Objective: Routine blood tests may provide useful information at different stages of epithelial ovarian cancer (EOC) management. This study evaluated continuous lactate dehydrogenase (LDH), carbohydrate antigen 125 (CA125), and neutrophil-to-lymphocyte ratio (NLR) values for diagnostic discrimination in epithelial ovarian cancer (EOC) and, separately, triple-positive status in relation to platinum resistance and survival. (2) Methods: This retrospective study included 238 patients with EOC and 238 individually matched patients with benign ovarian lesions. Continuous biomarkers were entered into logistic regression models for diagnosis. Triple-positive status was defined as LDH > 195.5 U/L, CA125 > 35.37 U/mL, and NLR > 2.63. Logistic regression was used for platinum resistance and Cox regression for progression-free survival (PFS) and overall survival (OS). Bootstrap internal validation was performed for the diagnostic models and PFS nomogram. (3) Results: The continuous LDH + CA125 + NLR model yielded an AUC of 0.873, with 75.97% sensitivity and 88.66% specificity; AUCs were 0.751 in early-stage and 0.958 in advanced-stage EOC. Adding NLR to LDH + CA125 did not significantly improve the AUC overall or within stage groups. Triple-positive status was associated with platinum resistance (adjusted OR = 3.488, 95% CI 1.504–8.087; p = 0.004), shorter PFS (adjusted HR = 3.109, 95% CI 1.772–5.456; p < 0.001), and shorter OS in advanced-stage EOC (adjusted HR = 3.538, 95% CI 1.385–9.038; p = 0.008). The PFS nomogram had a bootstrap-corrected C-index of 0.7521. (4) Conclusions: The continuous three-marker model showed diagnostic discrimination in this selected surgical cohort, while triple-positive status was associated with platinum resistance and adverse survival outcomes. External validation is needed. Full article

Protein variability patterns in cancer reflects both technical variation and biological heterogeneity and may provide information beyond mean abundance changes. We analyzed protein-level coefficients of variation across four ovarian cancer proteomic datasets, comparing controls and cancer samples. We analyzed protein-level coefficients of variation (CVs) across four ovarian cancer proteomic datasets, comparing control and tumor samples. Among 7476 proteins, the median CV increased from 93% in controls to 126% in cancer, and the distributions differed significantly between the two groups (Wilcoxon p < 2.2 × 10⁻¹⁶; Kolmogorov–Smirnov p = 4.2 × 10⁻²⁴²). The largest increases in variability were observed among proteins with low inter-individual variability in controls, whereas proteins that were already highly variable showed more heterogeneous behavior, including decreases in CV. Thus, cancer was associated not only with an overall increase in variability but also with a redistribution of proteins across variability states. Gene Ontology analysis revealed functional differences between stable and highly variable proteins. Stable proteins were predominantly associated with intracellular, organelle-related, biosynthetic, and metabolic processes, whereas highly variable proteins were more frequently linked to membrane, vesicle-related, and signaling functions. Proteins that remain stable from the control to cancer state, as well as those that lose this stability during tumor development, may therefore be of particular interest. These results support protein variability as an additional analytical dimension alongside fold-change analysis for describing proteome instability and tumor heterogeneity. Inter-individual variation in protein abundance may reflect biological heterogeneity that is not captured by conventional comparisons of mean expression levels. Variability analysis complements conventional abundance-based approaches and provides an additional framework for characterizing tumor proteome heterogeneity. Full article

Objective: Immune checkpoint inhibitor monotherapy has shown limited efficacy in platinum-resistant ovarian cancer (PROC), although a small subset of patients experiences durable disease control. We evaluated the association between baseline systemic inflammatory markers and the clinical outcomes of pembrolizumab monotherapy. Materials and Methods: We included 95 patients with PROC who received pembrolizumab monotherapy at Samsung Medical Center between 2018 and 2023. Durable disease control was defined as a progression-free survival (PFS) ≥ 6 months. The systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) were calculated from the pretreatment complete blood count. Associations with the PFS and overall survival (OS) were evaluated using multivariable Cox regression. Results: Among 94 patients evaluable for 6-month durable disease control, 10 (10.6%) achieved this endpoint. The patients with durable disease control had a lower baseline SIRI than those without durable disease control (median, 0.7 vs. 1.6; p = 0.019). In multivariable analyses, a higher log-transformed SIRI was associated with a shorter PFS (HR, 1.44; 95% CI, 1.13–1.83; p = 0.003) and OS (HR, 2.02; 95% CI, 1.53–2.67; p < 0.001). Conclusions: The baseline SIRI was associated with the PFS and OS in heavily pretreated patients with PROC receiving pembrolizumab monotherapy, and a lower SIRI was associated with durable disease control. The SIRI may provide readily available prognostic information in this setting; however, the data-derived cutoff requires prospective external validation and should not be interpreted as a predictor of the pembrolizumab-specific benefit. Full article

Ovarian cancer remains a major cause of gynecological cancer-related mortality, highlighting the need for novel therapeutic strategies capable of enhancing antitumor activity while targeting multiple mechanisms involved in tumor progression. Everolimus, an inhibitor of the mammalian target of rapamycin pathway, and carboplatin are established antineoplastic agents with distinct mechanisms of action, whereas astaxanthin is a bioactive carotenoid with antioxidant, anti-inflammatory, and potential anticancer properties. This study compared the individual and pairwise combination effects of carboplatin, everolimus, and astaxanthin on cell viability, migratory capacity, and inflammatory and tumor-associated biomarkers in SKOV3 ovarian cancer cells. Human SKOV3 ovarian cancer cells were cultured under standard conditions and exposed to different concentrations of carboplatin, everolimus, and astaxanthin, either individually or as pairwise two-drug combinations, for 24–72 h. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Cell migration was evaluated using a scratch wound-healing assay. Based on the experimental treatment protocol, 100 nM everolimus, 100 μM carboplatin, and 100 μM astaxanthin, alone and in combination, were further evaluated for their effects on β-defensin 1, β-defensin 2, α-defensin 1, tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) levels. Biomarker concentrations were determined by ELISA. Experiments were independently performed in triplicate. Everolimus, carboplatin, and astaxanthin produced concentration- and time-dependent alterations in SKOV3 cell viability, with more pronounced cytotoxic effects generally observed following prolonged exposure. The pairwise combination treatments also substantially affected cell viability, particularly at later experimental time points. Assessment of migratory capacity demonstrated significant differences in wound closure among treatment groups at 24, 48, and 72 h (p = 0.0224, p = 0.0155, and p = 0.0028, respectively), indicating a time-dependent inhibitory effect on SKOV3 cell migration. Treatment with carboplatin, everolimus, and astaxanthin, individually or in pairwise combinations, also significantly modulated β-defensin 1, β-defensin 2, α-defensin 1, TNF-α, and IL-1β levels compared with control cells, with the magnitude and direction of these changes varying according to treatment regimen and exposure duration. Everolimus, carboplatin, and astaxanthin exerted significant time- and treatment-dependent effects on the viability and migratory behavior of SKOV3 ovarian cancer cells and markedly modulated defensin and pro-inflammatory cytokine responses. The findings demonstrate distinct treatment- and time-dependent responses to the individual agents and their pairwise combinations in SKOV3 ovarian cancer cells. These observations represent preliminary comparative in vitro effects rather than evidence of pharmacological synergy or therapeutic benefit. Further mechanistic studies using additional ovarian cancer cell lines, formal drug interaction analyses, and in vivo models are required to establish the biological and potential therapeutic relevance of these treatment combinations. Full article

OVCAR3 cells are widely used to establish animal models of high-grade serous ovarian cancer (HGSOC) via subcutaneous (SC), intraperitoneal (IP), and intrabursal (IB) routes. However, direct comparisons of tumour development across these implantation routes are limited. This study compared the establishment, progression, dissemination and histological characteristics of SC, IP and IB OVCAR3 xenografts in female athymic nude mice over defined route-specific assessment periods. Tumour development was evaluated using semi-quantitative tumour scoring, histological assessment, nuclear morphometry and immunofluorescence staining for PAX8, WT1 and Ki67. IP and IB routes achieved 100% engraftment whereas SC implantation achieved engraftment in 15 of 18 animals. IP produced rapid carcinomatosis by Week 2, IB produced localised ovarian growth before contralateral spread, and SC produced confined stromal-encapsulated tumours. Mechanical confinement in the IB niche increased intratumoural density (1087 cells/mm²) and compressed single-cell nuclear area (22 µm²) compared to IP/SC models. Histological and immunofluorescence assessment demonstrated tumour expression of PAX8, WT1 and Ki67 across the three models, with route-associated differences in tumour organisation and staining distribution. Nuclear morphometric measurements varied among the models, although the between-route differences were not statistically significant. Together, these findings define the principal characteristics and progression patterns of three commonly used OVCAR3 implantation models and provide a practical framework for selecting the route and experimental timeframe most appropriate to the aims of future studies. Full article

Background: Platinum resistance remains a major therapeutic challenge in epithelial ovarian cancer (EOC). The tumour–stroma ratio (TSR) has emerged as a potential histopathological marker of tumour biology, but its clinical significance in different clinical settings remains unclear. We evaluated the association between stromal proportion, assessed using the TSR methodology, platinum resistance, and survival outcomes in patients undergoing primary debulking surgery (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT+IDS). Methods: This retrospective study included 83 patients with epithelial ovarian cancer (EOC) who underwent either primary debulking surgery (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (NACT+IDS) between 2017 and 2024. Patients were analysed separately according to treatment strategy. Stromal proportion was assessed on primary surgical specimens in the PDS cohort and on pretreatment diagnostic biopsy specimens in the NACT+IDS cohort. For this retrospective analysis, platinum resistance was operationally defined as recurrence within six months after completion of first-line platinum-based chemotherapy. Survival outcomes were analysed using the Kaplan–Meier method, and univariable binary logistic regression was performed separately within the PDS and NACT+IDS cohorts to explore the association between stromal category and platinum resistance. Results: Platinum resistance occurred in 25.3% of patients. In the PDS cohort, stromal category was not associated with clinicopathological characteristics, platinum resistance, disease-free survival (DFS), or overall survival (OS). In the NACT+IDS cohort, patients in the stroma-high group had a numerically higher rate of platinum resistance than those in the stroma-low group (57.9% vs. 22.2%; Fisher’s exact p = 0.114). Based on univariable logistic regression analysis, the stroma-high group had higher estimated odds of platinum resistance (OR 4.81, 95% CI 0.78–29.40), although this finding did not reach statistical significance (p = 0.090). No significant association was observed between stromal category and survival outcomes in either cohort. Conclusions: In the NACT+IDS cohort, patients in the stroma-high group had a numerically higher rate of platinum resistance than those in the stroma-low group; however, this difference did not reach statistical significance. These results should be interpreted with caution due to the retrospective study design and limited sample size; however, they nonetheless support further investigation of pretreatment TSR as a simple and easily applicable histopathological parameter in EOC. Larger prospective multicentre studies are required to determine whether this exploratory signal is reproducible and clinically relevant. Full article

Ovarian cancer remains difficult to detect before dissemination, and individual circulating biomarkers are unlikely to capture its biological and clinical heterogeneity. Multimodal liquid biopsy offers a potential route forward, but most biomarker combinations are developed empirically, with limited consideration of the molecular relationships among the measured signals. In this Perspective, we propose that intracellular miRNA dysregulation may provide an organizing layer for integrating glycoprotein/glycan remodeling with blood-derived volatile organic compound (VOC) signatures, while corresponding circulating miRNA profiles constitute a distinct measurable biomarker layer that may only partially reflect the underlying intracellular regulatory state. The miRNA–glycosylation axis is supported by direct mechanistic evidence that selected miRNAs regulate glycogenes and pathways controlling fucosylation, sialylation, and other glycan features. By contrast, the proposed connection between miRNA dysregulation and VOC production is indirect and likely mediated through metabolic reprogramming, mitochondrial dysfunction, oxidative stress, ferroptosis, and lipid peroxidation. We evaluate the evidence supporting each biomarker domain, prioritize candidate bridge miRNAs, including members of the miR-200 family and miR-34a, and define the principal boundary conditions of the framework, including causal inference, disease specificity, histological heterogeneity, VOC source ambiguity, temporal variability, and cross-platform standardization. We further outline a translational strategy based on matched biospecimens, mechanism-aware computational integration, experimental perturbation, longitudinal analysis, and independent validation at clinically relevant specificity thresholds. The objective is not to assert a fixed causal chain, but to provide a testable, clinically oriented framework for moving multimodal ovarian cancer diagnostics from statistical combination to biologically informed integration. Full article

Background: Endometriosis-associated ovarian cancers (EAOCs), including ovarian clear cell (OCCC) and endometrioid ovarian carcinoma (EnOC) subtypes, frequently exhibit transcriptomic dysregulation of the PI3K/AKT/mTOR signalling axis. While genomic aberrations are well-documented, the coordinated microRNA (miRNA)-mediated networks governing post-transcriptional remodelling of this pathway across these subtypes remain poorly defined. Methods: We conducted an integrative in silico meta-analysis of independent mRNA and small RNA sequencing datasets. The mRNA analysis included 120 EAOC samples, of which 68 were OCCC and 52 were EnOC, compared with 149 normal ovarian tissues. The miRNA analysis included 170 samples comprising 55 OCCC, 82 EnOC and 33 normal ovarian tissues. Differential expression analysis, dimensionality reduction (UMAP), functional enrichment, and topologically unweighted miRNA–mRNA interaction networks were evaluated. Results: Both subtypes showed significant transcriptomic dysregulation of the core pathway machinery, including PIK3CB and mTOR, while preserving mTORC2 components. Post-transcriptional concurrent downregulation of IRS1, GRB10, DDIT4, and PIK3CD, which were identified as candidate targets of the hub miRNAs hsa-miR-30a-5p, hsa-miR-30d-5p, and hsa-miR-7-5p, suggests further refined control of the pathway. The identification of highly connected hub genes linking mTOR, MAPK, and Wnt signalling pathways within the mTOR-regulatory network suggests that pathway modulation occurs through extensive crosstalk across multiple oncogenic signalling pathways in EAOCs. Conclusions: Transcriptomic dysregulation of the mTOR pathway in EAOCs reflects not only genomic alterations but also potential post-transcriptional regulation. Despite subtype-specific transcriptomic differences, both exhibited transcriptional upregulation of components of the canonical PI3K/AKT/mTOR signalling axis. Pathway modulation through the miRNA regulatory network exhibited potential crosstalk across oncogenic pathways and hub genes. Full article

Objective: Ovarian, fallopian tube, and primary peritoneal cancers remain among the deadliest gynecological malignancies, largely because most cases are diagnosed at an advanced stage and no effective screening strategy is currently available. Increasing evidence suggests that many high-grade serous ovarian carcinomas originate from the fallopian tube. We aimed to explore the diagnostic performance of ex vivo fallopian tube cytology and the CytoSaLPs score for detecting tubal and adnexal malignancies in women undergoing salpingectomy or salpingo-oophorectomy. Methods: We conducted a prospective single-center observational study including 304 women undergoing salpingectomy or salpingo-oophorectomy for benign, premalignant or malignant gynecological indications between 2020 and 2023. Ex vivo cytological brushing of the distal fallopian tube was performed before fixation, followed by histopathological examination using the SEE-FIM protocol where appropriate. The primary analysis was performed at the specimen level. Of 544 paired specimens initially available for cytology–histology correlation, 53 non-diagnostic cytological specimens were excluded from the primary diagnostic performance analysis, leaving 491 evaluable paired specimens. Fallopian tube cytological findings were compared with histopathology as the reference standard. The discriminatory ability of the CytoSaLPs score was explored using receiver operating characteristic analysis. Results: Fallopian tube cytology demonstrated high sensitivity for histologically confirmed tubal malignancy, although specificity was moderate. Based on the primary specimen-level analysis, sensitivity was 94.4% and specificity was 71.0%. When fallopian tube cytology was compared with ovarian histology, sensitivity was 72.9% and specificity was 72.4%. For the adnexa considered as a single anatomical entity, sensitivity was 76.5% and specificity was 70.7%. The CytoSaLPs score showed good discriminatory ability for fallopian tube malignancy (AUC 0.8534), moderate discrimination for ovarian malignancy (AUC 0.6790), and fair discrimination for adnexal malignancy (AUC 0.730). The optimal score thresholds were derived from the same dataset and should therefore be considered provisional. Three serous tubal intraepithelial carcinoma lesions were identified histologically; two showed cytological abnormalities and elevated CytoSaLPs scores, whereas one specimen was non-diagnostic. Conclusions: This exploratory proof-of-concept study suggests that ex vivo fallopian tube and the CytoSaLPs score may provide a structured approach for detecting cytological abnormalities associated with tubal and adnexal malignancy. However, the findings were obtained in a tertiary gynecologic oncology population under ex vivo conditions, non-diagnostic specimens occurred in approximately 10% of samples, and the scoring system was developed and evaluated within the same cohort. Independent external validation and evaluation using clinically applicable in vivo sampling methods are required before any clinical implementation can be considered. Full article

Vernonia calvoana (VC), a commonly used medicinal plant in West Africa, has been shown by our research team to inhibit the proliferation of OVCAR-3 ovarian cancer cells through mechanisms involving oxidative stress, DNA damage, and S-phase cell cycle arrest. The objective of the current study was to elucidate the intrinsic apoptotic mechanisms triggered by VC fraction seven (VCF7). OVCAR-3 cells were treated with VCF7 (0, 8, 16, and 32 μg/mL) for a duration of 48 h. Apoptosis was assessed using Annexin V/Propidium Iodide (PI) staining followed by flow cytometry analysis. Mitochondrial membrane potential (ΔΨm) was assessed through JC-1 staining and confocal microscopy, while chromatin condensation was analyzed using DAPI staining. DNA fragmentation was examined by agarose gel electrophoresis. Caspase 3 activity was measured using flow cytometry. Protein expression levels of p53, Bcl-2, cytochrome c, caspase-9, and caspase-3 were determined by Western blot analysis, and mRNA expression levels of p53 and Bcl-2 were evaluated using qRT-PCR. VCF7 induced apoptosis in a concentration-dependent manner. Analysis using Annexin V/PI indicated an increase in apoptotic cell populations from 10.5% to 30%, along with a rise in necrotic cells from 7% to 50% across treatment concentrations. A modest, concentration-associated decrease in mitochondrial membrane potential was recorded (0.96-, 0.88-, and 0.85-fold at 8, 16, and 32 μg/mL, respectively; p < 0.05). DAPI staining validated the concentration-dependent chromatin condensation and nuclear fragmentation. The analysis of DNA fragmentation showed progressive internucleosomal degradation, appearing as a smear pattern with distinct fragments at elevated concentrations, indicative of concurrent apoptotic and necrotic cell death. The activation of caspase-3 reached a peak of 28% at 16 μg/mL. Western blot analysis indicated an upregulation of p53, a downregulation of Bcl-2, an increase in total cytochrome c protein levels, and an increased expression of caspase-9 and caspase-3 in a concentration-dependent manner. These findings were corroborated at the transcriptional level by qRT-PCR, which showed increased p53 mRNA and decreased Bcl-2 mRNA expression. Taken together, these results underscore the potential of VCF7 as a promising plant-derived anticancer agent and support the need for further preclinical and clinical studies in ovarian cancer. Full article

Background/Objectives: HER2-directed antibody–drug conjugates have expanded the clinical relevance of low-level HER2 expression. However, the prevalence and clinical significance of HER2-ultralow expression in gynecologic malignancies remain insufficiently defined. This study characterized the full spectrum of HER2 expression in endometrial carcinoma (EC) and high-grade serous ovarian carcinoma (HGSOC), including matched metastatic lesions. Methods: HER2 expression was assessed by immunohistochemistry in tissue microarrays from 117 EC and 52 HGSOC patients. Available matched metastatic lesions were analyzed in 23 EC and 18 HGSOC cases. HER2 expression was categorized as zero, ultralow, 1+, 2+, or 3+. Associations with clinicopathological parameters and progression-free survival were evaluated. Results: HER2-ultralow expression was common in primary tumors, occurring in 49/117 EC cases (41.9%) and 11/52 HGSOC cases (21.2%), whereas HER2 3+ expression was rare (EC: 2/117, 1.7%; HGSOC: 1/52, 1.9%). HER2 expression in primary tumors was associated with progression-free survival in both entities, with HER2-zero tumors showing the longest estimated progression-free survival. HER2 score discordance between matched primary tumors and metastases occurred in 16/23 EC cases (69.6%) and 8/18 HGSOC cases (44.4%). Conclusions: HER2-ultralow expression represents a frequent and previously underrecognized category in EC and HGSOC. While its prognostic impact remains limited, the high prevalence of HER2-ultralow tumors suggests potential relevance for future HER2-targeted therapeutic strategies. Prospective studies are needed to determine whether this subgroup may benefit from a HER2-targeted therapy. Full article

Breast cancer remains among the leading causes of incidence and mortality worldwide. Consequently, identifying new treatments and strategies is of critical importance. Evidence indicates that camptothecin and its derivatives may exert anticancer effects in various cancer cell lines, including colon, lung, and ovarian cancers. However, their effects in breast cancer are not yet fully understood. Prior theoretical studies employing docking and molecular dynamics suggest that camptothecin could bind to the HER2 and EGFR receptors, which are overexpressed in breast cancer cells. Investigating interactions between novel molecules with affinity for membrane receptors overexpressed in breast cancer is important for developing personalized therapies and for advancing strategies to selectively target nanomaterials to these cells for diagnostic and therapeutic purposes. This study evaluated the in silico and in vitro effects of camptothecin on the MCF-7 and MDA-MB-231 breast cancer cell lines. Our results show significant inhibition of proliferation and reduced migration at 24, 48, and 72 h in both cell lines. The theoretical analysis indicates high affinity of camptothecin for receptors overexpressed in breast cancer compared with current treatments. Full article

Background/Objectives: Endometrial polyps are a prevalent pathological condition within the uterine cavity. While the majority of lesions are classified as benign, histopathological examinations indicate a potential for malignant transformation occurring in 0.5–5% of cases. The present study aimed to evaluate the prevalence of endometrial carcinoma and pre-malignant histopathological findings (glandular hyperplasia without atypia and atypical glandular hyperplasia) associated with endometrial polyps and to identify pertinent risk factors among Polish women undergoing hysteroscopic polypectomy under local anesthesia. Methods: A retrospective cohort study was conducted at the Outpatient Hysteroscopy Center of the Heliodor Swiecicki University Hospital of Gynecology and Obstetrics, affiliated with Poznan University of Medical Sciences. The study included patients treated using the GUBBINI mini-resectoscope under local anesthesia with the Hystero-Block system (Tontarra Medizintechnik GmbH, Wurmlingen, Germany) between December 2022 and July 2026. Statistical analysis of risk factors was performed using the Kruskal–Wallis H test and Fisher’s exact test. Odds ratios for potential risk factors were also calculated. Results: The study comprised 2588 patients. Endometrial carcinoma associated with endometrial polyps was identified in 16 women (0.62%). Additional histopathological findings included glandular hyperplasia in 360 patients (13.91%) and atypical hyperplasia in 35 patients (1.35%), with the remaining patients diagnosed with benign uterine polyps (84.12%). Patients with malignant and pre-malignant lesions were significantly older than those with benign polyps (p < 0.001). Regarding polyp size, patients diagnosed with glandular hyperplasia without atypia had significantly larger polyps than those with benign lesions (p < 0.001). Estimated postmenopausal status was associated with significantly higher odds of endometrial carcinoma (Odds Ratio [OR] = 6.56, 95% Confidence Interval [CI]: 2.12–20.30, p = 0.001) and atypical glandular hyperplasia (OR = 3.13, 95% CI: 1.41–6.96, p = 0.005) compared to benign polyps. Similarly, obesity increased the odds of glandular hyperplasia without atypia (OR = 1.32, 95% CI: 1.01–1.74, p = 0.045) and atypical glandular hyperplasia (OR = 3.33, 95% CI: 1.67–6.65, p < 0.001). Furthermore, hypertension was associated with higher odds of glandular hyperplasia without atypia compared to benign polyps (OR = 1.41, 95% CI: 1.02–1.97, p = 0.040). Other evaluated risk factors, including type II diabetes mellitus, infertility, abnormal uterine bleeding, breast cancer history, hypothyroidism and polyendocrine metabolic ovarian syndrome (PMOS), did not reach statistical significance (p > 0.05). This large cohort provides important data regarding the prevalence and risk factors of carcinoma associated with endometrial polyps and pre-malignant uterine lesions in Polish women. Conclusions: Endometrial carcinoma associated with endometrial polyps is a rare entity among Polish women undergoing outpatient hysteroscopy (0.62%). Nevertheless, the primary diagnostic value of this large-scale study lies in demonstrating that despite the low prevalence of malignancy in standard “see-and-treat” outpatient settings, systematic histopathological evaluation remains an absolute diagnostic mandate, as relying solely on visual or clinical parameters is insufficient to exclude malignancy. Furthermore, identified risk factors, such as age, polyp size, estimated postmenopausal status, obesity and hypertension, serve as critical diagnostic red flags, associated with increased odds of concurrent premalignant lesions or carcinoma. Full article