Search Results (376)

Background: The fibrous tumor extracellular matrix (ECM), driven by cancer-associated fibroblasts (CAFs), forms a physical barrier against drugs and immune cells, yet direct CAF elimination risks promoting metastasis. Methods: In this study, we developed a locally injectable hydrogel based on synergistic dynamic covalent crosslinking (imine and boronate ester bonds), enabling instant gelation, shear thinning, and dual-pH/ROS-responsive degradation. Two types of drug-loaded nanoparticles (NPs), coated with homotypic cell membranes, were incorporated into this hydrogel. In the acidic, reactive oxygen species (ROS)-rich tumor microenvironment (TME), the system responsively releases the antifibrotic drug SIS3 to reprogram CAFs while simultaneously delivering doxorubicin (DOX) specifically to tumor cells. Biological effects were evaluated in vitro using cell cultures and in vivo in mouse models. Results: This dynamic hydrogel-based co-delivery system effectively reprograms CAFs, reduces tumor mechanical stress, breaks the fibrotic barrier, and promotes the deep infiltration of chemotherapeutics and immune cells, thereby enhancing the efficacy of chemotherapy. Conclusions: This injectable pH/ROS-responsive dynamic covalent hydrogel, loaded with CAF- and cancer cell-targeting NPs, remodels the TME, enhances drug and immune cell penetration, and offers a promising biomaterial-based strategy for cervical cancer treatment. Full article

Background/Objectives: Parapharyngeal space (PPS) metastases from thyroid carcinoma are rare, and evidence guiding their surgical management, particularly the role of concomitant lateral neck dissection (LND) in patients with a clinically node-negative (cN0) neck, remains limited. This systematic review and patient-level analysis evaluated the clinicopathological characteristics, surgical management, and oncologic outcomes of PPS metastases, with particular emphasis on the management of the cN0 neck. Methods: A PRISMA 2020-compliant systematic review of PubMed, Scopus, and the Cochrane Library was performed. Patient-level data were analyzed according to clinical neck status and timing of PPS metastasis presentation. Results: Thirty-two studies including 162 patients were analyzed. Papillary thyroid carcinoma accounted for 94.4% of cases, while PPS metastases presented as primary disease in 48.8% and recurrent disease in 51.2% of patients. The transcervical approach (TCA) was the predominant surgical technique (79.1%), whereas LND was performed in 70.2% of patients with available data. Among the 19 patients with a cN0 neck, 10 had a previously undissected lateral neck; of these, 6 underwent elective LND and 4 underwent isolated PPS metastasectomy. No occult cervical lymph node metastases were identified following elective LND. Patients with recurrent PPS metastases had significantly higher overall recurrence (47.5% vs. 13.2%, p < 0.001) and disease-specific mortality (22.8% vs. 5.6%, p = 0.003) than those with primary PPS metastases. Conclusions: TCA remains the reference surgical strategy for PPS metastases from thyroid carcinoma. Although based on a very limited cN0 subgroup, current evidence suggests that routine elective LND may not be necessary in carefully selected patients presenting with isolated PPS metastases and a cN0 neck. Recurrent PPS metastases are associated with poorer oncologic outcomes. Full article

Objectives: The endometrium and cervix share a common Müllerian origin and may exhibit overlapping biological responses to oncogenic stimuli. However, the clinical significance of preoperative cervical cytology in patients with endometrial cancer remains unclear. This study aimed to investigate the association between preoperative cervical smear cytology and clinicopathologic characteristics, with particular emphasis on advanced FIGO stage (III–IV) as the primary outcome. Methods: This retrospective cohort study included 154 patients who underwent primary surgery for histologically confirmed endometrial cancer. Preoperative cervical smear cytology was classified according to the Bethesda System into four categories: normal, low-grade, high-grade, and malignant. For subgroup analyses, low-grade, high-grade, and malignant cytology results were combined and compared with normal cytology. FIGO stage was analyzed both as individual stages (IA–IV) and as early-stage (I–II) versus advanced-stage (III–IV) disease, where appropriate. Continuous variables were summarized as mean ± standard deviation or median (interquartile range), while categorical variables were expressed as n (%). Group comparisons were performed using the Pearson chi-square test or Fisher’s exact test, as appropriate, and a two-sided p value < 0.05 was considered statistically significant. Results: A total of 154 patients with endometrial cancer were included in the analysis. Preoperative cervical smear cytology was normal in 140 patients (90.9%), low-grade in 6 (3.9%), high-grade in 3 (1.9%), and malignant in 5 (3.2%). Comparison across cytology categories demonstrated a significant association between smear cytology and FIGO stage (p < 0.001), with high-grade and malignant cytology occurring more frequently in patients with advanced-stage disease. Vaginal cuff involvement was also significantly associated with smear cytology (p = 0.001), whereas no significant associations were observed for myometrial invasion, lymphovascular space invasion, cervical stromal involvement, tubo-ovarian involvement, omental involvement, or lymph node metastasis. Subgroup analysis comparing normal and abnormal cytology yielded similar findings, confirming significant associations with FIGO stage (p < 0.001) and vaginal cuff involvement (p = 0.002). In a multivariable model additionally including cervical cytology, LVSI and deep myometrial invasion were independent predictors of advanced stage (AUC = 0.888), whereas cytology was not statistically significant after adjustment (OR 4.51, p = 0.076) and showed poor standalone diagnostic performance (AUC = 0.564, sensitivity 19.4%, specificity 93.5%). All patients with vaginal cuff involvement had advanced-stage disease (Fisher’s exact p < 0.001). The cytology–FIGO stage association was not significant in postmenopausal (p = 0.065) or endometrioid-only (p = 1.00) subgroup analyses. Conclusions: Abnormal preoperative cervical smear cytology was significantly associated with advanced FIGO stage and vaginal cuff involvement in patients with endometrial cancer. These findings suggest that cervical cytological abnormalities may reflect overall disease extent rather than individual histopathological risk factors. Given the retrospective design and the limited number of patients with abnormal cytology, these findings should be interpreted cautiously and validated in larger prospective studies. However, cytology was not an independent predictor of advanced stage after multivariable adjustment and performed poorly as a standalone diagnostic marker, suggesting it should not be used alone to assess disease extent. Full article

MicroRNAs (miRNAs) have been associated with the initiation, development, and progression of various cancers, including cervical cancer. Their involvement in cervical cancer is extensively documented, as they influence critical biological pathways, including apoptosis, cell cycle progression, immune evasion, and metastasis. In cervical cancer, deregulated miRNA expression contributes to tumor aggressiveness by interfering with key molecular pathways, many of which are also influenced by high-risk human papillomavirus (HPV) oncoproteins. In this review, we highlight key signaling pathways regulated by miRNAs linked to cancer hallmarks, particularly sustained proliferative signaling, which was the most frequently affected pathway across the studies reviewed. Furthermore, the interplay among HPV oncoproteins, dysregulated miRNA expression, and altered signaling pathways drives key oncogenic processes, including uncontrolled proliferation, evasion of apoptosis, and metastasis. Full article

Small cell carcinoma of the cervix (SCCC) is a rare yet highly aggressive subtype of cervical cancer (CC), characterized by early invasion, high metastatic potential, frequent recurrence, and extremely poor prognosis, which severely impairs women’s physical and mental health. Currently, high-risk human papillomavirus (hr-HPV, particularly HPV18) infection is recognized as one of the core drivers underlying the initiation and progression of SCCC. Malignant evolution is not triggered by a single infection event but is cooperatively regulated at multiple molecular levels, including HPV genome integration, critical gene mutations, and aberrant activation of multiple signaling pathways. In addition, SCCC exhibits an HPV-independent oncogenic pathway mainly mediated by somatic mutations in tumor protein 53 (TP53) and retinoblastoma 1 (RB1), thus forming a dual pathogenic mechanism. Based on current clinical understanding and molecular mechanisms, this paper reviews the molecular pathogenesis and subtypes of SCCC, reveals the associations between tumor heterogeneity, therapeutic resistance, and metastasis, and proposes potential novel targets for the treatment of SCCC. This study innovatively presents a closed-loop model of two-way empowerment between basic research and clinical application. It emphasizes that basic research should be oriented toward real clinical problems and highlights the reciprocal feedback of clinical practice on basic research, thereby achieving dynamic iteration and collaborative breakthroughs in both fields. Full article

Background: Human papillomavirus (HPV) infection defines a distinct subtype of head and neck squamous cell carcinoma (HNSCC). Although HPV-positive (HPV+) HNSCC generally shows better overall survival than HPV-negative (HPV−) disease, it is frequently associated with cervical lymph node metastasis. However, the epithelial cell states and viral gene-associated mechanisms underlying HPV−related metastatic progression remain incompletely understood. This study aimed to identify metastasis-associated epithelial subpopulations in HPV+ HNSCC and explore the potential role of HPV16 E7 in regulating metastatic programs. Methods: Public single-cell RNA-sequencing datasets from paired primary and metastatic HNSCC samples were integrated and analyzed to characterize malignant epithelial subpopulations. Copy number variation (CNV) inference, clustering, pathway enrichment, stemness scoring, and trajectory analysis were performed to define metastasis-associated epithelial states. TCGA transcriptomic data and tissue-based validation were used to support candidate gene screening. In vitro functional assays were performed using SERPINB3-knockdown and HPV16 early gene-overexpressing CAL27 cell models. Results: Single-cell analysis identified stem-like metastatic epithelial subpopulations in HPV+ and HPV− HNSCC. In HPV+ metastatic lesions, an ALDH2+/LAMB3+ epithelial subpopulation showed elevated epithelial–mesenchymal transition activity and stem-like features. SERPINB3 displayed a dynamic expression pattern during HPV+ metastatic progression. Functional assays showed that SERPINB3 knockdown enhanced CAL27 cell migration and invasion and was associated with activation of MYC- and epithelial–mesenchymal transition-related transcriptional programs. Among HPV16 early genes, E5, E6, E6*, and E7 showed different degrees of SERPINB3 suppression, while E7-expressing cells exhibited distinct transcriptional alterations associated with epithelial plasticity and metastatic-related programs. Conclusions: This study identifies a stem-like metastatic epithelial state in HPV-associated HNSCC and suggests a potential HPV16 early gene-SERPINB3-MYC-related regulatory mechanism involved in metastatic epithelial plasticity. Full article

Background/Objectives: Image-guided adaptive brachytherapy is a core component of definitive treatment for locally advanced cervical cancer (LACC). However, implantation remains challenging in bulky, asymmetric, or anatomically complex tumors, where standard applicator geometry or purely straight interstitial trajectories may be insufficient for individualized target coverage. This study evaluated the real-world implementation of a patient-specific 3D-printed template-guided adaptive brachytherapy workflow for complex LACC. Methods: We retrospectively reviewed 120 consecutive patients with FIGO 2018 stage IB3–IVA cervical cancer treated with definitive chemoradiotherapy followed by high-dose-rate image-guided brachytherapy between March 2023 and March 2025. All patients were treated using a patient-specific 3D-printed template-guided hybrid intracavitary/interstitial workflow integrating CT/MRI-based target assessment, individualized catheter trajectory planning, template fabrication, implantation verification, and adaptive treatment planning. Straight-channel or curved-channel guidance was selected according to residual tumor geometry and pelvic anatomy, with flexible plastic interstitial catheters used for curved or anatomically constrained trajectories. Procedural deliverability, dosimetry, toxicity, early clinical outcomes, and exploratory dose–outcome patterns were analyzed. Results: The median HR-CTV volume was 55.9 cm³, and the median HR-CTV D90 was 92.9 Gy EQD2. Median organ-at-risk D2cc values remained within contemporary institutional and guideline-consistent constraints. A total of 555 template-guided HDR brachytherapy fractions were delivered. The median applicator-and-catheter placement time was 4.21 min per fraction, with a median of 7.25 implanted channels. Minor and major insertion-related bleeding occurred in 10.8% and 1.7% of patients, respectively. At a median follow-up of 20.1 months, estimated 3-year overall survival, progression-free survival, local recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival were 77.9%, 76.8%, 94.3%, 98.0%, and 86.2%, respectively. Late grade ≥ 3 gastrointestinal and genitourinary toxicities occurred in 2.5% and 1.7% of patients, respectively, with no grade 4–5 events. Exploratory dose–outcome analyses suggested hypothesis-generating dose–outcome patterns, but these findings were not intended to define or validate a clinical dose threshold. Conclusions: This real-world implementation study supports the feasibility of patient-specific 3D-printed template-guided adaptive brachytherapy for complex LACC. By translating CT/MRI-based individualized trajectory planning into template-guided intracavitary/interstitial catheter placement, this workflow achieved guideline-consistent target coverage, acceptable organ-at-risk doses, efficient procedural delivery, and low severe toxicity within the available follow-up. Dose–outcome findings remain exploratory and require validation in more mature cohorts. Full article

Background/Objectives: Extra virgin olive oil (EVOO), a key component of the Mediterranean diet, has attracted research interest because olive-derived phenolics demonstrate potential anticancer activity in experimental models. This review summarizes evidence concerning whole EVOO, phenolic-enriched EVOO, olive phenolic extracts, and the isolated compounds hydroxytyrosol, oleuropein, oleocanthal, and oleacein. Methods: A structured narrative search of PubMed, Web of Science, ScienceDirect, and Google Scholar was conducted for literature published between 2015 and 2025. Evidence was reviewed for breast, prostate, colorectal, pancreatic, bone, oral, liver, gastric, hematological, and brain cancers. Comparatively limited evidence concerning cervical, endometrial, ovarian, melanoma, non-melanoma skin, and thyroid cancers was summarized separately. Results: The molecular evidence was derived primarily from cell culture and animal studies using isolated phenolics and concentrated extracts. Preclinical studies indicate that EVOO phenolics may demonstrate anticancer activity through multiple mechanisms, including antioxidant activity, anti-inflammatory effects, cell cycle arrest, induction of apoptosis, inhibition of metastasis, anti-angiogenic activity, and modulation of key signaling pathways, such as PI3K/AKT/mTOR, MAPK/ERK, NF-κB, JAK/STAT, Wnt/β-catenin, p53, and epithelial–mesenchymal transition-related pathways. Most molecular and pathway-level evidence was obtained using isolated phenolic compounds in cell culture or animal models, whereas evidence directly examining whole EVOO consumption was largely observational and substantially more limited. Experimental studies also reported that oleocanthal induced lysosomal membrane permeabilization, whereas hydroxytyrosol and oleuropein promoted mitochondria-mediated apoptosis. Furthermore, preclinical combination studies suggested enhanced tumor-cell sensitivity to selected chemotherapeutic, targeted, and immunotherapeutic agents. However, these effects have not been established in patients. Human evidence remains limited mainly to observational dietary associations and small exploratory interventions, with no conclusive demonstration of cancer prevention or therapeutic efficacy. Conclusions: Isolated EVOO-derived phenolic compounds demonstrated promising anticancer mechanisms in preclinical models. However, these results should not be directly extrapolated to dietary EVOO because experimentally administered doses, bioavailability, metabolism, and food-matrix interactions differ substantially from human dietary exposure. Therefore, well-designed studies using chemically characterized EVOO, pharmacokinetic investigations, and controlled human trials are required before dietary or clinical recommendations can be made. Full article

Background/Objectives: Thymidylate synthase (TYMS) represents an important therapeutic target. Methods: In this study, TYMS expression was analyzed by immunohistochemistry on a tissue microarray containing 17,371 samples from 136 different tumor types. Results: TYMS staining was seen in 42.9% of 15,361 analyzable tumors, with weak staining in 35.4%, moderate in 5.7%, and strong in 1.8%. TYMS occurred in at least one case of 127 categories, of which 71 showed TYMS staining in at least 50% of cases, and 56 included at least one case with strong positivity. TYMS positivity occurred most commonly in lymphomas (81.3–96.5%), sarcomas and sarcomatoid carcinomas (33.3–100%), malignant melanoma (70.5–90.7%), cervical adenocarcinoma (78.3%), and squamous cell carcinomas of various sites (57.1–77.9%). High TYMS expression was linked to advanced pT (p = 0.0097), high grade (p < 0.0001), ER negativity (p < 0.0001), and PR negativity (p = 0.0002) in invasive breast cancer of no special type; high grade (p < 0.0050), high UICC stage (p = 0.0060), and nodal metastasis (p = 0.0120) in clear cell renal cell carcinoma (RCC); high grade (p < 0.05) and nodal metastasis (p = 0.0045) in papillary RCC; high Gleason grade (p < 0.0001) and advanced pT stage (p = 0.0149) in prostatic adenocarcinoma; high pT (p < 0.0001), nodal metastasis (p = 0.005), lymphatic (p = 0.0064) and venous invasion (p = 0.0005), left side location (p < 0.0001), and microsatellite instability (p < 0.0001) in colorectal adenocarcinoma; and high grade (p < 0.0001) in squamous cell carcinomas of different sites. Conclusions: TYMS is often overexpressed across different cancer entities and shows associations with several adverse histopathological parameters commonly used to describe tumor phenotypes. Full article

Background/Objectives: Occult cervical nodal metastasis drives prognosis in oral cavity squamous cell carcinoma (OCSCC), yet current tools for risk stratification in clinically node-negative (cN0) patients are imperfect. Machine learning (ML) models have been proposed to refine selection for elective neck dissection (END), but their diagnostic performance and generalizability are unclear. Methods: We performed a diagnostic test accuracy systematic review and meta-analysis of ML models predicting occult nodal metastasis in adults with cN0 OCSCC. Eligible studies evaluated an ML-based model, used pathologic nodal status as the reference standard, and reported or allowed reconstruction of sensitivity and specificity. Internal and external validation were distinguished; quantitative synthesis was restricted to non-overlapping external validation cohorts. Diagnostic performance was synthesized with a bivariate random-effects hierarchical summary receiver operating characteristic (HSROC) model, with prespecified sensitivity analyses restricting to lower-risk patient-selection cohorts, models using only preoperative predictors, and non-outlying cohorts. Results: Thirteen retrospective studies (4730 patients) met inclusion; pooled occult nodal metastasis prevalence was 23.6% (crude 20.4%). Eight studies reported only internal validation; five provided six external validation cohorts. Across these external cohorts, pooled sensitivity was 0.79 (95% CI, 0.64–0.89) and specificity 0.84 (95% CI, 0.70–0.93). Negative predictive values were consistently high (0.94–0.98), whereas positive predictive values were modest (0.39–0.85). Sensitivity analyses yielded similar summary estimates with wider confidence intervals. Conclusions: Externally validated ML models for predicting occult nodal metastasis in cN0 OCSCC show promise but remain insufficiently validated to guide END in routine practice. Full article

Background/Objectives: Following the LACC trial, the role of minimally invasive radical surgery for early-stage cervical cancer remains controversial. Robotic-assisted approaches have been proposed as a potential strategy to preserve the benefits of minimally invasive surgery while incorporating contemporary oncologic precautions. This study compared perioperative, pathological, and early oncologic outcomes between robotic and open radical surgical management in patients with FIGO 2018 stage IA2–IIA1 cervical cancer. Methods: Patients underwent robotic surgery (n = 20; da Vinci Xi), including robotic radical hysterectomy, compartment-based procedures, and fertility-sparing surgery when clinically indicated, or open abdominal radical hysterectomy (n = 22). Perioperative outcomes, histopathological parameters (including lymphovascular space invasion [LVSI], lymph node status, and margin status), and early oncologic outcomes were evaluated. Exploratory multivariable regression analyses were performed to adjust for baseline differences, including age and tumor size. Results: Patients in the open-surgery cohort were older (56.23 ± 15.87 vs. 45.67 ± 9.31 years; p = 0.012) and had significantly larger tumors (3.07 ± 1.10 vs. 1.4 ± 0.7 cm; p = 0.003). Robotic surgery was associated with longer operative time (178 ± 42 vs. 150 ± 38 min; p = 0.028), lower blood loss (112 ± 61 vs. 518 ± 98 mL; p < 0.001), and shorter hospital stay (4.2 ± 1.6 vs. 6.2 ± 1.4 days; p < 0.001). The robotic cohort also demonstrated a higher lymph node yield (median 18 vs. 9; p < 0.001). No statistically significant differences were observed between groups in lymph node metastasis (20.0% vs. 22.7%; p = 1.000), LVSI (33.3% vs. 63.6%; p = 0.121), or R0 resection rate (100% vs. 95.5%; p = 1.000). In exploratory adjusted analyses, surgical approach was not associated with adverse pathological features, whereas tumor size emerged as an independent predictor of both lymph node metastasis and LVSI. No recurrences were observed in the robotic cohort during the available follow-up period. Conclusions: In this exploratory comparative cohort study, robotic radical surgical management in carefully selected patients with predominantly small-volume disease was associated with favorable perioperative outcomes and no statistically significant differences in pathological parameters compared with open surgery. Tumor size, rather than surgical approach, emerged as the principal predictor of adverse pathological features. Given the limited sample size, baseline imbalances between cohorts, heterogeneous robotic procedures, and absence of mature survival data, these findings should not be interpreted as evidence of oncologic equivalence and require confirmation in larger prospective studies. Full article

Background/Objectives: Cancer, a multifactorial disease with uncontrolled cell growth, oxidative stress, inflammation, genomic instability, and molecular signaling pathways, is a global health concern, leading to the ~20 million newly diagnosed cases annually. Although conventional therapy has been shown to enhance the survival rates of cancer patients, its clinical efficacy is limited by certain side effects that occur as a result of treatment, thus necessitating the exploration of plant-derived bioactive compounds for their potential as safer and alternative supportive therapeutic agents. Aloe vera, known as the plant of immortality, comprises phytochemicals, such as anthraquinones (aloe-emodin, emodin, and aloin), polysaccharides (acemannan), flavonoids, and phenolic acids, which contribute to the pharmacological effect of the compound. Methods: This review summarizes the anticancer potential of Aloe vera, and the data were retrieved from databases, such as PubMed, Google Scholar, ScienceDirect, Web of Science, and Wiley Online Library, during the time period of 2015 to 2025. Results: The literature revealed that Aloe vera and its bioactive compounds have dose-dependent cytotoxic and anti-proliferative properties against hepatocellular, cervical, colorectal, lung, breast, prostate, and hematological cancers, which are significantly mediated by apoptosis and pyroptosis induction, reactive oxygen species (ROS) production, mitochondrial dysfunction, inhibition of angiogenesis and metastasis, and the modulation of key signaling pathways, particularly PI3K/Akt, MAPK, NF-кB, p53, and Wnt/β-catenin. Furthermore, anthraquinones, including Aloe-emodin, demonstrate potent anticancer effects at micro-molar doses, and polysaccharides increase immune reactions and provide tumor immunity. Conclusions: Conclusively, Aloe vera is a promising multi-target natural compound, particularly efficient in the treatment of cancer. However, despite significant therapeutic potential, more research on pharmacokinetics, standard dose, and controlled clinical trials of Aloe vera is required to validate clinical applicability. Full article

Background and Objectives: Uterine metastasis from breast carcinoma is rare but poses substantial diagnostic and therapeutic challenges. Invasive lobular carcinoma (ILC) demonstrates a documented predilection for unusual metastatic patterns including the female genital tract, while tamoxifen-associated endometrial pathology may complicate diagnosis in breast cancer survivors. Materials and Methods: We performed a structured PubMed/MEDLINE and Google Scholar search (1980–2025) for cases with histologically confirmed breast primary and uterine involvement; a pooled analysis of demographic, histological, molecular, and clinical variables was performed. Results: 105 individual cases were identified. ILC accounted for 58.0% of histologically classified cases despite representing only 10–15% of breast cancers. Endometrial involvement was present in 68.6%, myometrial in 25.7%, and cervical in 26.7%. Tamoxifen exposure was strongly associated with polyp-substrate metastasis (29.3% vs. 4.7%; Fisher’s exact p = 0.0009; OR 8.41, 95% CI 2.20–32.14). Abnormal uterine bleeding was the dominant presentation (68.1%); 19.8% were asymptomatic. Median latency was 36 months (range from 24 months before to 360 months after the breast cancer diagnosis). Conclusions: Uterine metastasis from breast carcinoma is dominated by invasive lobular histology and frequently involves tamoxifen-associated polyps. A combined immunohistochemical panel (GATA3, TRPS1, E-cadherin, hormone receptors, PAX8) is essential for distinguishing metastatic disease from primary uterine pathology. Endometrial sampling should be considered with a low threshold in breast cancer survivors with abnormal uterine bleeding, and breast imaging is warranted when discohesive cells are encountered without a known breast primary. These proportions describe the published case literature rather than population-based prevalence; because the evidence is limited to case reports and small series, they should not be read as the true frequency of uterine involvement among women with breast cancer. Full article

Background: Metastases to the uterine cervix from extragenital malignancies represent uncommon clinical events, with breast invasive lobular carcinoma (ILC) documented as the predominant primary source in reported literature. Objectives/Aim: To characterize the clinicopathologic features of ILCs metastatic to the uterine cervix. Methods: We performed a PubMed search using several keywords. Results: A total of 29 studies were included in the final analysis. The mean age at presentation of cervical metastasis was 56.8 ± 2.0 years. The mean interval between the initial diagnosis of ILC and the detection of cervical metastasis was 55.6 ± 8.2 months. Clinical presentations included vaginal bleeding, pelvic pain, and unhealthy enlarged, indurated uterine cervix on local examination. The diagnosis was established via tissue biopsy and immunohistochemical stains (positive reactivity for CK7, ER, PR, E-Cadherin, GATA3, GCDP-15 and mammaglobin). There are no consensus treatment protocols, and therapy should be tailored individually based on the extent of disease. Combined surgical and systemic therapy was the most commonly used modality. Conclusions: Metastasis of breast ILCs to the uterine cervix poses a significant diagnostic challenge. A high index of clinical suspicion and detailed clinical history are essential for accurate diagnosis. Full article

Matrilysins and stromelysins play a vital role in cancer, facilitating tumor invasion and metastasis. The aim of this study was to investigate the diagnostic significance of selected matrilysins and stromelysins in comparison to routine tumor markers in gynecological malignancies, relative to a control group (benign tumors and healthy women). Preoperative plasma levels of selected metalloproteinases were determined using ELISA, while levels of CA125, SCC-Ag, and HE4 by CMIA. In endometrial and cervical cancers, matrilysins (MMP-7 and MMP-26) exhibited higher diagnostic utility than routine markers. Similarly, all stromelysins in cervical cancer outperformed CA125; furthermore, MMP-10 also outperformed SCC-Ag, achieving the highest diagnostic utility among all parameters tested in cervical cancer. For ovarian cancer, diagnostic utility remained highest for routine markers. In endometrial and cervical cancers, the AUCs for all studied parameters exceeded those of standard markers, while in ovarian cancer, MMP-7 had an AUC higher than HE4 and comparable to CA 125. Combined analysis of the studied parameters in diagnostic panels demonstrated that their introduction into routine diagnostics could provide tangible benefits in the detection of malignant gynecological lesions, especially the combination of MMP-7 or MMP-10 with routine markers. These results indicate the usefulness and high diagnostic power of selected MMPs in the detection of these malignancies. Full article