Search Results (1,210)

Cartilage oligomeric matrix protein (COMP) influences extracellular matrix remodeling. We investigated its clinical, prognostic, and immunomodulatory significance in colorectal cancer (CRC). COMP was quantified via ELISA in 107 paired CRC and normal tissues. Expression was correlated with clinicopathological features, mutational profiles, microsatellite instability (MSI), tumor-infiltrating lymphocytes (TILs), immune checkpoints, and multiplex cytokine networks. For transcriptomic validation, the FieldEffectCrc dataset was used for Gene Set Enrichment Analysis (GSEA), and The Cancer Genome Atlas (TCGA) CRC cohort for survival analysis. COMP was significantly upregulated in CRC tissues (p < 0.001) and correlated with advanced T, N, and overall pathological stages (all p < 0.05, tau = 0.18, 0.21, and 0.23, respectively). High COMP expression was linked to restricted immune infiltration (reduced stromal TILs, p < 0.05, tau = −0.23), elevated levels in microsatellite stable (MSS) compared to MSI tumors (p < 0.01), and correlated positively with immune exhaustion markers (T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), galectin-9 (GAL9), sialic acid-binding Ig-like lectin 9 (SIGLEC9)). Transcriptomic data linked high COMP to worse disease-specific and progression-free survival, and enrichment in pro-tumorigenic pathways (epithelial-to-mesenchymal transition, angiogenesis, IL-6 signaling). COMP upregulation defines an immunosuppressive microenvironment in CRC, particularly in MSS tumors. It represents an important prognostic biomarker and potential therapeutic target for overcoming immunotherapy resistance. Full article

Background: KRAS mutations are among the most common oncogenic drivers in non-small cell lung cancer (NSCLC) and are associated with substantial molecular and immunological heterogeneity. However, the clinicopathological associations and prognostic relevance of KRAS mutation subtypes and co-occurring genomic alterations in relation to PD-L1 expression and survival outcomes remain incompletely understood, particularly in the immunotherapy era. Methods: This retrospective single-center study included 93 KRAS-mutant NSCLC patients identified among 543 consecutively sequenced cases between March 2024 and March 2025. KRAS mutation subtypes, co-mutations involving TP53, STK11, and KEAP1, PD-L1 expression status, clinicopathological features, and survival outcomes were evaluated. Overall survival was assessed using Kaplan–Meier analysis and Cox proportional hazards regression models. Results: KRAS mutations were detected in 17.1% of NSCLC patients. G12C was the most frequent KRAS subtype (38.7%), followed by G12V (18.3%) and G12D (14.0%). Co-occurring mutations were identified in 73.1% of cases, most commonly involving TP53 (40.9%) and STK11 (33.3%). PD-L1 expression was negative in 48.4% of patients, low in 28.0%, and high in 23.7%. No significant association was identified between KRAS mutation subtype and PD-L1 expression (p = 0.663). STK11-mutated tumors demonstrated a trend toward lower PD-L1 expression levels compared with STK11 wild-type tumors. However, none of the molecular variables retained independent prognostic significance. Immunotherapy was associated with significantly prolonged overall survival (median OS: 24 vs. 7 months, p = 0.013) and remained independently associated with improved survival in multivariate analysis (HR: 0.376, 95% CI: 0.204–0.694, p = 0.002). Advanced-stage disease independently predicted worse survival outcomes (HR: 13.43, 95% CI: 1.81–99.79, p = 0.011). Conclusions: KRAS mutation subtypes and co-occurring genomic alterations demonstrated limited independent prognostic significance in this real-world NSCLC cohort. In contrast, immunotherapy was associated with improved overall survival in this retrospective cohort. These findings should be interpreted as observational and hypothesis-generating rather than evidence of predictive treatment benefit. Larger prospective studies integrating genomic and immune biomarkers are warranted. Full article

Background and Clinical Significance: Beta-propeller protein–associated neurodegeneration (BPAN), also known as static encephalopathy of childhood with neurodegeneration in adulthood (SENDA), is a subtype of neurodegeneration with brain iron accumulation caused by pathogenic variants in WDR45. Although its clinical course and neuroimaging features are increasingly recognized, detailed neuropathological characterization, especially at its terminal stage, remains limited. Case presentation: We report a 68-year-old woman with a heterozygous WDR45 splice-site variant (NM_007075.4:c.830+1G>A), representing the longest-surviving case of SENDA/BPAN described to date. After static developmental delay in childhood, she rapidly developed progressive parkinsonism, dystonia, and cognitive decline in early adulthood, ultimately becoming bedridden with profound motor and autonomic dysfunction. Serial MRI demonstrated progressive cerebral and cerebellar atrophy with iron-related signal changes in the globus pallidus and substantia nigra. She died of sepsis at the age of 68 and was subjected to an autopsy including the brain. Neuropathological findings: Autopsy revealed severe, diffuse neuronal loss and gliosis throughout the central nervous system, with marked iron deposition and complete neuronal loss in the globus pallidus and substantia nigra. Immunohistochemistry demonstrated widespread tau pathology. Notably, neuronal tau inclusions contained both four-repeat (4R) and three-repeat (3R) isoforms, whereas glial tau was predominantly 4R-positive, indicating a mixed neuronal 4R/3R and glial 4R-dominant tauopathy. Perivascular and subpial 4R-tau–dominant deposits consistent with aging-related tau astrogliopathy were also present. LC3-positive and ferritin-positive cells suggested impaired autophagic flux, supporting the proposed autophagy-related pathogenesis of SENDA/BPAN. Conclusions: This case provides comprehensive clinicopathological insight into end-stage SENDA/BPAN, highlighting distinctive tau isoform patterns in neurons versus glia and pathological evidence of autophagy dysfunction. These findings expand the neuropathological spectrum of SENDA/BPAN and may inform future mechanistic and therapeutic research. Full article

Background/Objectives: Facial discoid dermatosis is a rare inflammatory dermatosis presenting with round, superficial erythematous lesions located on the face. Diagnosis may be challenging and often requires careful clinicopathological correlation due to overlapping clinical and histopathological features. Skin lesions are typically resistant to a wide range of topical and systemic treatments. From the perspective of personalized medicine, improved phenotyping of rare inflammatory dermatoses may support more precise diagnosis, individualized therapeutic decisions, and non-invasive disease monitoring. This study aimed to characterize facial discoid dermatosis using line-field confocal optical coherence tomography and reflectance confocal microscopy and to discuss its differential diagnosis and therapeutic implications. Methods: We report a case of facial discoid dermatosis in a 35-year-old patient examined with line-field confocal optical coherence tomography and reflectance confocal microscopy. The imaging findings were interpreted in correlation with clinical and histopathological features. A literature review was performed to summarize differential diagnoses, therapeutic perspectives, and the proposed relationship between facial discoid dermatosis and pityriasis rubra pilaris. Results: Non-invasive imaging revealed morphological features consistent with a psoriasiform inflammatory dermatosis and provided additional in vivo information supporting the diagnosis. The literature review showed limited evidence for a direct association between facial discoid dermatosis and pityriasis rubra pilaris, with only isolated reports suggesting possible overlap or progression. Conclusions: Facial discoid dermatosis appears to represent a distinct psoriasiform dermatosis. Line-field confocal optical coherence tomography and reflectance confocal microscopy may contribute to a personalized diagnostic approach by supporting differential diagnosis and potentially guiding individualized monitoring in rare inflammatory facial dermatoses. Full article

Background and Objectives: Identifying regulatory genes that integrate epigenetic, transcriptional, immune, and non-coding RNA networks may improve prognostic stratification in hepatocellular carcinoma (HCC). ZBTB40 is a poorly characterized transcription factor whose clinical relevance and multi-layered regulatory role in HCC remain unclear. This study systematically investigated the prognostic significance, molecular regulatory networks, and toxicogenomic interactions of ZBTB40 in HCC. Materials and Methods: Comprehensive multi-omics analyses were conducted utilizing TCGA-HCC datasets and various public bioinformatics platforms. We systematically evaluated ZBTB40 expression patterns, survival outcomes, clinicopathological associations, DNA methylation status, immune cell infiltration, and competing endogenous RNA (ceRNA) networks. Additionally, chemical–gene interactions were analyzed using the Comparative Toxicogenomics Database (CTD). Results: ZBTB40 was significantly overexpressed in HCC, closely correlating with advanced clinicopathological features and poor survival outcomes. This upregulation was significantly associated with promoter hypomethylation. Furthermore, ZBTB40 expression was associated with specific immune infiltration patterns. A ZBTB40-centered ceRNA network identified key regulatory miRNAs, including miR-24-3p, miR-34a-5p, miR-132-3p, and miR-222-3p, along with prognostically relevant lncRNAs and circRNAs. CTD analysis identified 39 key chemical modulators of ZBTB40 (e.g., sorafenib, aflatoxin B1) and revealed RNF13 and CHD3 as functionally related genes sharing substantial chemical interaction profiles. Functional analyses suggested ZBTB40’s involvement in chromatin remodeling, the cell cycle, and immune-related pathways. Conclusions: ZBTB40 expression is associated with multi-layered molecular features involving epigenetic, post-transcriptional, immune-related, and toxicogenomic signatures in HCC. Full article

To evaluate the diagnostic performance and clinicopathologic relevance of a multi-locus circulating tumor DNA methylation assay, in this prospective, single-center, case-control exploratory study, we enrolled 35 patients with colorectal cancer undergoing surgery and 57 healthy controls undergoing screening colonoscopy at the Asan Medical Center, Seoul, Republic of Korea between July 2024 and January 2025. Peripheral blood was collected before surgery or colonoscopy, and circulating tumor DNA methylation was analyzed using a multi-locus panel targeting Septin9, IKZF1, BCAT1, Septin9-2, BCAN, and VAV3. The main outcomes were test accuracy (sensitivity, specificity, and area under the curve [AUC]) and associations between methylation marker positivity and clinicopathologic features. Circulating tumor DNA was positive in 74.3% of the patients and 12.3% of controls, yielding a sensitivity of 74.3%, specificity of 87.7%, and an AUC of 0.837, whereas serum carcinoembryonic antigen exhibited lower sensitivity (25.7%). Sensitivity in stage I disease was limited (36.4%). Circulating tumor DNA-positive tumors were larger (5.7 cm vs. 2.2 cm, p < 0.001) and had more advanced T and N stages. The number of positive markers increased with pathologic stage (p = 0.003). Individual marker analysis revealed that BCAT1, Septin9-2, and VAV3 were associated with higher T stage, whereas BCAN positivity was linked to nodal metastasis. The six-marker circulating tumor DNA methylation assay demonstrated acceptable diagnostic accuracy, with multi-locus patterns associated with tumor burden and invasive features. However, sensitivity for early-stage disease was limited. The assay may serve as a complementary tool for screening and risk stratification. Full article

Background/Objectives: Pediatric IgA nephropathy (IgAN) is often considered to have a favorable early course. However, its progression is variable, and the prognostic value of histopathological classifications, such as MEST-C, remains incompletely defined in children. This study aimed to characterize clinicopathological features and the early disease course in pediatric IgAN and to descriptively examine histopathological findings and clinical outcomes. Methods: This retrospective, single-center study included children with biopsy-confirmed IgAN diagnosed between 2016 and 2025. Clinical, laboratory, and histopathological data were collected, and biopsies were assessed using the Oxford MEST-C classification. Follow-up data, including estimated glomerular filtration rate (eGFR), were analyzed descriptively, with follow-up extending from diagnosis to early 2026. Results: Fourteen patients were included, showing heterogeneous clinical presentations. Mesangial hypercellularity was observed in all cases (100%), with frequent endocapillary hypercellularity (78.6%) and segmental sclerosis (57.1%), consistent with a predominance of active lesions. Over a median follow-up of approximately five years, renal function remained stable in 57.1% of patients, declined in 21.4%, and improved in 14.3%, indicating variability in renal function during follow-up and potential reversibility in a subset of patients. One patient (7.1%) developed severe acute kidney injury requiring temporary dialysis, followed by full recovery. Given the descriptive design and limited sample size, no conclusions regarding associations between histopathological findings and renal outcomes can be drawn. Conclusions: Within this small cohort, pediatric IgAN showed variable renal function courses ranging from stability to decline or partial recovery. These findings should be considered descriptive and hypothesis-generating, supporting longitudinal monitoring in larger pediatric cohorts. Full article

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is a biologically heterogeneous disease. Beyond VHL inactivation, alterations in chromatin remodeling genes BAP1 and PBRM1 define distinct tumor phenotypes with prognostic implications. We sought to characterize the clinicopathological features and oncological outcomes associated with IHC-defined loss of these markers in a contemporary surgical cohort. Methods: We retrospectively analyzed 214 patients undergoing partial or radical nephrectomy for ccRCC (2010–2021). Loss of BAP1 and PBRM1 expression was assessed by automated immunohistochemistry. Tumors with retained expression were classified as wild-type and compared with those showing loss of at least one marker. Survival outcomes were evaluated using Kaplan–Meier analysis, multivariable Cox models, and Restricted Mean Survival Time (RMST). Results: IHC-defined loss was identified in 19 patients (8.9%): BAP1 in 12 (5.6%) and PBRM1 in 7 (3.3%). Tumors with IHC-defined loss showed more aggressive features, including larger size (7.7 vs. 4.7 cm; p = 0.009), higher necrosis (36.8% vs. 18.5%; p = 0.050), and more advanced stage (pT3–pT4: 47.4% vs. 16.4%; p < 0.001). Kaplan–Meier analysis demonstrated significantly worse survival outcomes in the IHC-loss group across all endpoints (p ≤ 0.011). RMST analysis at 60 months confirmed significantly worse outcomes across all endpoints (p ≤ 0.005). Conclusions: Loss of BAP1 or PBRM1 identifies a biologically aggressive ccRCC subset with worse oncological outcomes. IHC-based molecular profiling is a practical and accessible tool for risk stratification in surgically treated ccRCC. 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

Background/Objectives: There remains a need for additional prognostic markers in classic follicular lymphoma (cFL) to identify aggressive disease. Immunohistochemical stains such as Ki-67, MYC, and p53 have shown variable associations with histologic grade and adverse outcomes. In this study, we aimed to assess intrafollicular Ki-67, MYC, and p53 expression in cFL via immunohistochemistry, quantified by both manual and digital methods, and evaluate their relation to histologic grade and clinical outcomes. Methods: We evaluated 37 cases of cFL from 2000 to 2019 and performed immunohistochemistry for Ki-67, MYC, and p53 on tumor microarray tissue. Stains were assessed within follicles by digital pathology means on QuPath software and via manual low-power estimates. Results:MYC expression was greater in FL3A compared to FL1–2 across all digital and manual scoring methods (all p < 0.05). Ki-67 and p53 expression did not differ by histologic grade group. No biomarker showed a significant association with adverse clinicopathologic features or outcomes, including FLIPI risk group, bulky disease, clinical stage, event-free survival, or overall survival. Manual and digital scores demonstrated strong correlations for all markers (ρ = 0.71–0.89, all p < 0.001). Conclusions: In our cohort, MYC expression was increased in FL3A compared to FL1–2, while no intrafollicular biomarker measurement was associated with adverse clinicopathologic features or clinical outcomes in exploratory analyses. These findings should be interpreted with caution in light of our limited cohort size. Strong concordance between manual and digital scoring supports the feasibility of digital IHC quantification in cFL. Full article

Background: The tumor immune microenvironment, particularly the role of cytotoxic CD8+ T lymphocytes, is crucial in cancer progression but remains poorly understood in pituitary neuroendocrine tumors (PitNETs). The significance of CD8+ cell infiltration varies across PitNET subtypes, suggesting a complex interplay with tumor cell lineage. This study aimed to characterize the distribution of CD8+ tumor-infiltrating lymphocytes across different PitNET subtypes defined by the current WHO classification and to explore their association with clinicopathological features. Methods: We conducted a retrospective study on 40 surgically resected PitNETs. All cases were classified based on immunohistochemical expression of pituitary hormones and lineage-specific transcription factors (PIT-1, TPIT, SF-1). CD8+ lymphocyte density was quantified using immunohistochemistry and calculated as cells/mm². Exploratory statistical analysis was performed based on non-parametric tests to compare CD8+ cell density across tumor subtypes and with parameters like tumor size, invasiveness (Knosp grade), and proliferation index (Ki-67). Findings are to be treated as observational trends. Results: The highest density of CD8+ lymphocytes was observed in plurihormonal PIT-1-positive tumors [17.61 cells/mm² (IQR: 17.61–60.36)], followed by somatotroph [13.2 (6.6–15.72)] and mammosomatotroph [13.83 (0–21.38)] tumors. A difference in CD8+ density was found between PIT-1-positive and PIT-1-negative tumors (n1 = 34, n2 = 6, U = 49.5, p_exact = 0.050, r = 0.33); the medium effect size indicates a possible lineage-related trend. Another difference was observed between SF-1-positive and SF-1-negative tumors (p = 0.025), with SF-1 lineage tumors showing the lowest infiltration. No correlations were found between CD8+ density and tumor size, Knosp grade, or Ki-67 index. Conclusions: The distribution of intratumoral CD8+ T lymphocytes in PitNETs is highly heterogeneous and appears to be strongly dictated by the transcription factor-defined tumor lineage rather than by traditional clinicopathological markers of aggressiveness. PIT-1 lineage tumors harbor a more active immune microenvironment, while SF-1 lineage tumors are relatively ‘immune-poor’. These findings highlight the immunological diversity of PitNETs and support further investigation of the tumor immune landscape. Collaborative multi-institutional studies are required to validate these trends. Full article

This study aimed to investigate the expression of immune checkpoint-associated proteins in phyllodes tumors (PTs) and assess their clinicopathologic and prognostic significance. Surgical resection specimens from 200 patients were included, and the expressions of CD24, Siglec-10, CD47, and SIRPα in both the epithelial and stromal components of the tumor were assessed, with ≥1% positivity considered positive. Of 200 cases, 145 were benign, 44 borderline, and 11 malignant. The expressions of CD24, Siglec-10, CD47, and SIRPα in stromal cells increased with tumor grade: CD24 was associated with stromal cellularity, atypia, and mitosis; Siglec-10 with stromal cellularity and atypia; CD47 with stromal atypia and mitosis; and SIRPα with stromal overgrowth and atypia. While expressions of CD24, CD47, and SIRPα were associated with either shorter disease-free survival (DFS) or shorter overall survival, multivariate analysis identified stromal CD24 expression as an independent predictor of shorter DFS. Immune checkpoint-associated proteins, particularly stromal CD24, CD47, and SIRPα, are associated with adverse features and poor outcomes in PTs, implicating potential prognostic and therapeutic relevance. Full article

Background/Objectives: Oral tongue squamous cell carcinoma (OTSCC) remains clinically challenging because conventional clinicopathological markers do not fully explain variability in recurrence and survival. This systematic review and functional meta-synthesis aimed to identify and critically appraise studies using preoperative magnetic resonance imaging (MRI)-based radiomics, artificial intelligence (AI), deep learning, or quantitative MRI-derived models to predict recurrence and prognostic outcomes in OTSCC. Methods: PubMed, Scopus, and Embase were searched from inception to March 2026. Eligible studies included prognostic model investigations in adults with OTSCC or primary tongue cancer without reported base-of-tongue/oropharyngeal involvement, undergoing preoperative MRI and surgery, with recurrence- or survival-related follow-up. The primary synthesis was a functional meta-synthesis; pooling was not performed because studies were not sufficiently comparable. Results: Seven retrospective studies were included, with a summed descriptive sample of 1287 participants. The evidence base was heterogeneous in MRI sequences, segmentation workflows, model architecture, validation strategy, and endpoint definition. Functional meta-synthesis identified four domains: direct recurrence-oriented modeling, broader prognostic stratification, reported incremental or complementary value over clinical frameworks, and translational maturity/technical implementation. Several studies reported associations between MRI-derived signatures and recurrence- or survival-related outcomes, but findings were interpreted narratively because of differences in primary endpoints, imaging features, model design, validation methods, and outcome definitions. Most studies were judged at high overall risk of bias, and certainty of evidence ranged from low to very low. Conclusions: MRI-based radiomics and AI show preliminary promise for prognostic stratification in OTSCC, particularly recurrence-related risk refinement, but current evidence remains limited by retrospective design, heterogeneity, sparse external validation, and low certainty. Full article

Background/Objectives: High-grade B-cell lymphomas (HGBCLs) with MYC and BCL2 or BCL6 translocations, colloquially referred to as double-hit lymphomas (and abbreviated here to DHL), are aggressive malignancies. Differentiating DHL from non-DHL HGBCLs is important, as DHL patients may benefit from more intensive treatment regimes. We aimed to identify predictive clinicopathological, morphological, and immunophenotypic features that could guide selection of HGBCLs for fluorescence in situ hybridization (FISH), which is expensive and less accessible in some centers. Methods: We conducted a PRISMA systematic review and meta-analysis on 29 studies identified from four databases (PubMed (MEDLINE), Ovid (Embase), Web of Science, and Scopus). We calculated risk ratios (RRs) to compare features between DHL and non-DHL HGBCL and between MYC/BCL2 and MYC/BCL6 DHL patients. Results: DHL patients were associated with higher Ann Arbor stage (RR 1.15, p = 0.028, I² = 38.7%), International Prognostic Index (IPI) score (RR 1.27, p = 0.047, I² = 37.9%), elevated lactate dehydrogenase (RR 1.26, p = 0.012, I² = 34.0%), and germinal center B-cell-like (GCB) immunophenotype (RR 1.21, p = 0.043, I² = 35.8%) compared to non-DHL HGBCL patients. c-Myc immunopositivity, extranodal disease, and bone marrow involvement were more likely in DHL, albeit not reaching statistical significance. Extranodal disease (p = 0.015, I² = 0.0%), central nervous system involvement (p = 0.044, I² = 0.0%), and non-GCB immunophenotype (p = 0.016, I² = 71.1%) were more likely in MYC/BCL6 compared to MYC/BCL2 DHL patients. BCL2 immunopositivity, CD10 immunopositivity, and MUM1 immunonegativity were more likely in MYC/BCL2 DHL, although the differences were not statistically significant. Conclusions: Our results have associated DHL with features of aggressive disease and found GCB immunophenotype as a histopathological feature with statistically significant predictive value for MYC/BCL2 DHL. Heterogeneity within the non-DHL HGBCL group and variation in immunohistochemical cut-off values between studies limited identification of other predictive features. Larger, consistently designed, prospective cohort studies could provide further evidence for a screening strategy for DHL. Full article

Background/Objectives: Metabolic syndrome is a prevalent global health concern characterized by central obesity, insulin resistance, hypertension, and dyslipidemia. Growing evidence suggests that metabolic dysregulation may influence prostate cancer risk and disease behavior; however, findings across studies remain inconsistent. This systematic review aimed to evaluate the association between metabolic syndrome and prostate cancer risk, clinicopathologic characteristics, and disease outcomes. Methods: A systematic literature search was conducted in PubMed/MEDLINE from database inception through the final search update on 10 January 2026, with supplementary searches of Google Scholar, Wiley Online Library, the Clinical Oncology journal collection, and reference lists. Observational studies assessing the relationship between metabolic syndrome and prostate cancer outcomes were eligible for inclusion. Two reviewers independently screened titles and abstracts, followed by full text review to determine eligibility. Discrepancies were resolved through consensus. Risk of bias was assessed using design-specific tools, including the Newcastle–Ottawa Scale, Cochrane Risk of Bias 2 tool, and Joanna Briggs Institute checklist. Findings were synthesized narratively because of heterogeneity in study design, metabolic syndrome definitions, populations, outcomes, and effect estimates. Results: A total of 1304 records were identified across all databases. After duplicate assessment, records underwent title and abstract screening, followed by full text assessment. Twenty-four studies, ranging from small clinic-based cohorts to large population-based cohorts exceeding 5 million participants, met the inclusion criteria and were included in the qualitative synthesis. Most studies were cohort or case–control designs conducted in North America, Europe, and Asia. Overall, evidence for a uniform association between composite metabolic syndrome and prostate cancer incidence was inconsistent. Associations appeared more suggestive for clinically significant, high-grade, or adverse pathological features, although findings varied by study design, metabolic syndrome definition, detection context, and adjustment level. Several studies suggested that individual components of metabolic syndrome, particularly obesity and insulin resistance, may be key drivers of these associations. Conclusions: Available evidence suggests a heterogeneous relationship between metabolic syndrome, related metabolic abnormalities, and prostate cancer outcomes. Evidence for a uniform association with overall prostate cancer incidence was inconsistent, whereas signals were more frequently reported for clinically significant, high-grade, or adverse pathological features. However, these findings should be interpreted cautiously because of observational study designs, heterogeneous MetS definitions, detection context, and variable adjustment. Further well-designed prospective studies are needed to clarify temporality, causal pathways, and the contributions of individual metabolic components. Full article