Search Results (1,129)

Background/Objectives: Advanced renal cell carcinoma (aRCC) remains incurable, with no established optimal sequence of targeted therapies due to interpatient heterogeneity and acquired resistance. We developed a luciferase-enabled patient-derived orthotopic xenograft (PDOX) avatar platform to evaluate sequential targeted therapies in individualized aRCC models that recapitulate tumor architecture, proliferation, angiogenesis, metastasis, and PD-L1 expression. Methods: Tumor specimens from two renal cell carcinoma (RCC) patients were expanded subcutaneously in NOD/SCID mice, transduced with luciferase/red fluorescent protein (Luc/RFP), and orthotopically implanted into mouse kidneys (KiCa-Pt58: sarcomatoid RCC, pT3aN1M1, Fuhrman grade 4; KiCa-Pt118: clear cell RCC with sarcomatoid component, pT3aNxM0, Fuhrman grade 4, respectively). Tumor growth and metastasis were monitored weekly by bioluminescence imaging (BLI). Mice were randomized into vehicle control or four sequential treatment groups (Everolimus→Sunitinib [E→S], Sunitinib→Everolimus [S→E], Pazopanib→Sunitinib [P→S], Pazopanib→Everolimus [P→E]). Drugs were administered orally three times weekly until resistance (>200% BLI increase), with one switch. At necropsy, tumor burden, ex vivo BLI metastasis, weights, H&E histology, and immunohistochemistry (Ki67, CD44, CD31, PD-L1) were assessed. Results: Two independent experiments were performed. In dosing optimization, PDOX tumors recapitulated parental histology and proliferative indices, mirroring patient trajectories. KiCa-Pt58 (metastatic sarcomatoid RCC; deceased 1-month post-nephrectomy) showed aggressive features: rapid engraftment at low doses, early growth (week 2), and lung metastases in 78% of mice (sacrifice day 34), reflecting a fulminant course. KiCa-Pt118 (non-metastatic; patient recurrence-free >8 years post nephrectomy) exhibited indolent behavior: delayed engraftment requiring higher doses plus lymph node stromal (HK) support, slower growth (week 4), no metastases, and later sacrifice (day 78), consistent with remission. In sequential therapy evaluation, for KiCa-Pt58, P→E yielded greatest reductions in tumor weight (p < 0.01), lung metastases (p < 0.01), Ki67+ proliferation, CD31+ angiogenesis, and PD-L1 expression versus control; E→S and S→E were also effective. For KiCa-Pt118, S→E and P→E reduced tumor burden (p < 0.01) and Ki67⁺ proliferation; S→E lowered CD31 and PD-L1. Conclusions: This RCC PDOX platform faithfully preserves patient-specific biology—including metastatic propensity, engraftment efficiency, growth kinetics, and stromal dependency—while enabling real-time evaluation of sequential targeted therapies. Given the limited number of models tested, these findings provide proof-of-concept for individualized treatment exploration in advanced RCC and support future investigation of rational combinations with immune checkpoint blockade in humanized or immunocompetent systems. Full article

Background/Objectives: Ovarian epithelial cancers (EOCs) comprise heterogeneous subtypes with distinct clinical outcomes, making accurate histological subtyping essential for prognosis and treatment planning. Although deep learning using digitized hematoxylin and eosin (H&E) whole-slide images (WSIs) is now widely used, its application to ovarian cancer diagnosis remains limited. Methods: In this multicenter study, we analyzed 319 H&E-stained slides from 152 patients with surgically resected EOC. An attention-based multiple instance learning (MIL) framework built on a pathology-specific foundation model (UNI) was used. WSIs were divided into 512 × 512-pixel patches at 40× magnification, and slide-level classification were generated through attention-based aggregation of patch-level feature, followed by patient-level prediction. External validation was performed specifically on the high-grade serous carcinoma (HGSC) cases from The Cancer Genome Atlas (TCGA) dataset. Results: The model achieved strong performance, with slide-level and patient-level accuracies of 0.918 and 0.900, respectively, on the test set. In five-fold cross-validation, the mean slide-level AUC was 0.990 (95% CI: 0.983–0.997), and the patient-level AUC was 0.993 (95% CI: 0.989–0.996), indicating consistent results. External validation on TCGA HGSC cases showed robust generalizability, with slide-level and patient-level accuracies of 0.794 and 0.898. F1-scores ranged from 0.832 to 1.000 at the slide-level and from 0.831 to 0.966 at the patient-level, with particularly strong performance for HGSC and clear-cell carcinoma. Conclusions: These findings demonstrate the feasibility of deep learning-based models for histological subtyping of EOC using H&E-stained WSIs. This approach may help pathologists achieve more accurate and consistent histological diagnoses of EOC. Full article

Background: Pathological upstaging (PU) of clear cell renal cell carcinoma (ccRCC) from clinical cT1 to pT3 stage often requires conversion from partial to radical nephrectomy. Preoperative PU prediction lacks objective, precise methods, hindering surgical decision−making. Methods: We developed and validated a computed tomography−based radiomics ensemble learning model (CRIPEM) integrating intratumoral and peritumoral features to predict PU in cT1 ccRCC. We enrolled a multicenter cohort of 309 cT1 ccRCC patients from three institutions, divided into training (n = 170), internal validation (n = 73), and external validation (n = 66) cohorts. Bioinformatics analysis confirmed that peritumoral regions harbor critical predictive value for PU. Results: A total of 7336 radiomic features were extracted from intratumoral and peritumoral (1, 2, 3 mm) regions on preoperative CT images, with 50 robust features retained via a rigorous five−step selection process. CRIPEM, fusing optimal base learners (IT−MLP for intratumoral features, PT1−RF for 1−mm peritumoral features), achieved area under the curve values of 0.872, 0.807, and 0.826 in the training, internal, and external validation cohorts, respectively. Subgroup, calibration, and decision curve analyses confirmed its stability, superiority over single base learners, and significant clinical net benefits, with individualized cases verifying clinical applicability. Conclusions: CRIPEM is an objective, accurate, and robust tool for preoperative PU prediction in cT1 ccRCC, which can optimize surgical strategy selection and improve patient clinical management. Full article

Spontaneous regression of metastatic renal cell carcinoma is a rare and incompletely understood phenomenon. We report the case of a 61-year-old man with biopsy-proven pulmonary metastases from clear cell renal cell carcinoma who experienced durable tumor regression without receiving any systemic therapy. The patient underwent cryoablation of a symptomatic iliac bone metastasis and discontinued methotrexate, previously prescribed for inflammatory polyarthritis. Serial imaging demonstrated initial slow progression followed by significant shrinkage of pulmonary and mediastinal lesions, leading to a sustained partial response according to RECIST 1.1 criteria. No disease progression has been observed after extended follow-up. Two non-mutually exclusive mechanisms may explain this observation: restoration of antitumor immunity following withdrawal of immunosuppressive therapy, and a systemic immune response triggered by local tumor destruction (abscopal effect). Although such events are exceptional, this case highlights the potential interplay between immune modulation and local therapies in renal cell carcinoma. Further investigation is warranted to better understand these mechanisms and their potential therapeutic implications. Full article

Metastasis is a primary driver of poor outcomes in clear cell renal cell carcinoma (ccRCC), yet the role of Aquaporin-9 (AQP9) in this process remains unclear. This study aimed to investigate the function, clinical significance, and therapeutic potential of AQP9 in ccRCC. AQP9 expression was analyzed using TCGA data and validated in human tissues and cell lines via Western blot. Functional assays assessed malignant behaviors, while bioinformatics and rescue experiments explored the involvement of the JAK/STAT pathway and epithelial–mesenchymal transition (EMT). Virtual screening, molecular docking, and cellular thermal shift assays (CETSAs) were employed to identify Tedizolid as a potential AQP9 inhibitor, followed by functional validation in vitro and in a xenograft model. AQP9 was significantly upregulated in ccRCC and associated with poor prognosis. The knockdown of AQP9 suppressed proliferation, migration, invasion, and EMT, whereas its overexpression promoted these effects by activating the JAK/STAT pathway. Tedizolid bound directly to AQP9, inhibited cell viability, reversed AQP9-induced malignant phenotypes, and suppressed JAK/STAT signaling both in vitro and in vivo. In conclusion, AQP9 promotes ccRCC metastasis through the JAK/STAT-EMT axis and represents a potential prognostic biomarker and therapeutic target. Tedizolid, identified as a novel AQP9 inhibitor, offers a promising repurposed strategy for ccRCC treatment. Full article

Background/Objectives: To evaluate the clinical utility and diagnostic performance of quantitative MRI parameters (T1, T2*, R2*, and ADC) in differentiating renal tumor subtypes and WHO grades, and to assess their potential role in non-invasive tumor characterization. Methods: This retrospective study included 82 patients with histopathologically confirmed renal tumors who underwent preoperative contrast-enhanced MRI between July 2019 and January 2024. Quantitative measurements were obtained from tumor regions and contralateral healthy renal cortex using standardized ROI-based analysis. Parameters included T2*, native and post-contrast T1, R2* (1/T2*), and ADC values. Interobserver agreement was assessed. A Random Forest model was used as a supplementary analytical tool. Results: The cohort included 82 patients (mean age: 59.3 years). Tumors were classified into multiple subtypes, with clear cell carcinoma being the most common (n = 46). High-grade tumors (WHO grades 3–4) demonstrated significantly lower ADC values (p = 0.029) and larger tumor size (p = 0.0017). Significant differences in T2*, R2*, and ADC values were observed across tumor subtypes (p < 0.05). Quantitative MRI parameters demonstrated moderate discriminatory performance, with ADC emerging as the most robust biomarker. The Random Forest model achieved an overall accuracy of 93.2%, primarily driven by ADC and post-contrast T1 values. Conclusions: Quantitative MRI parameters, particularly ADC, provide clinically meaningful non-invasive biomarkers for renal tumor characterization. Their combined interpretation, supported by contralateral renal cortex comparison, may enhance clinical decision-making. Further validation in larger cohorts is warranted. Full article

Background and Objectives: Renal cell carcinoma (RCC) exhibits heterogeneous and sometimes unpredictable metastatic behavior, involving both common and uncommon anatomic sites. Institutional analyses of histopathologically confirmed metastatic RCC may improve diagnostic recognition and clinical awareness. This study aimed to characterize the metastatic distribution and histopathologic features of RCC diagnosed in a single tertiary center over a five-year period. Materials and Methods: A retrospective review of the pathology database of the Department of Pathology, “Pius Brînzeu” Emergency County Hospital, Timișoara, was performed to identify all histologically confirmed cases of metastatic RCC diagnosed between January 2020 and December 2024. Case identification was based on pathology reports of metastatic lesions. In a subset of cases, corresponding pathology reports of the primary renal tumor were available and reviewed. Histopathological data collected included WHO/ISUP grade, tumor necrosis, sarcomatoid and/or rhabdoid differentiation, vascular invasion, surgical margin status, tumor size, and pathological T stage (pT). Exploratory analyses were performed to assess associations between metastatic site and selected histopathological features. Results: Thirty-two cases of metastatic RCC were identified, all demonstrating clear cell morphology. The mean patient age was 62.9 years, with a marked male predominance. Among cases with available primary tumor data, high WHO/ISUP grade and adverse histopathologic features were frequently observed. The most common metastatic sites in our institution were the brain and bone, followed by the adrenal gland, lymph nodes, and liver. Less frequent metastatic involvement included the pancreas, testis, vagina, skin, and peritoneum. Exploratory analyses did not demonstrate statistically significant associations between metastatic site and tumor grade, necrosis, or sarcomatoid/rhabdoid differentiation; however, descriptive trends were observed, including the association of brain metastases with high-grade tumors and the high prevalence of tumor necrosis across metastatic sites. Conclusions: This pathology-based retrospective series highlights the broad metastatic spectrum of RCC, including both typical and rare anatomic sites. The predominance of clear cell morphology and the frequent association with adverse histopathologic features support the link between aggressive tumor biology and metastatic disease. Although no statistically significant associations were identified, the observed patterns suggest potential relationships between metastatic distribution and tumor characteristics, warranting further investigation in larger studies. Full article

Background: Clear cell renal cell carcinoma (CCRCC) is the predominant subtype of renal cell carcinoma and is characterized by frequent chromosome 3 alterations, including 3p deletion, monosomy, and aneuploidy. However, the absence of standardized fluorescence in situ hybridization (FISH) cut-off values has led to inconsistent reported frequencies and limited clinical integration of this accessible assay. This study aimed to establish clinically applicable cut-off values, propose a practical three-tier classification, and evaluate its diagnostic accuracy and clinicomolecular correlation with tumor aggressiveness. Methods: FISH using VHL (3p25.3) and CEP3 probes was performed on 1748 RCC cases (1655 CCRCC, 48 papillary RCC, 45 chromophobe RCC). Cut-off values were determined by combining ROC analysis with Youden’s index and the mean + 3SD method from normal renal tubular cells. A paired cohort of 97 CCRCC cases with targeted next-generation sequencing was stratified into three subgroups (3p intact, isolated 3p loss, broad chr3 change) for clinicomolecular comparison, including 3D principal component analysis. Results: Clinically applicable thresholds of 30% for 3p deletion and 20% for monosomy identified chromosome 3 alterations in 76.9% of CCRCC cases. The combination of both markers achieved superior diagnostic accuracy (AUC = 0.82). Aneuploidy was significantly associated with higher WHO/ISUP grade (p < 0.001) and older age (p = 0.006). The three-tier classification showed stepwise progression of aggressive features (older age, higher grade, larger tumor size) and increasing PBRM1 mutation frequency from the 3p intact to the broad chr3 change group. Conclusions: This study establishes standardized FISH cut-offs and a practical three-tier classification that captures a continuous spectrum of genomic instability and tumor aggressiveness in CCRCC. Routine 3p FISH provides a simple, cost-effective, and reproducible tool with substantial diagnostic and stratification value that complements more complex genomic profiling. Full article

Renal cell carcinoma (RCC) is acknowledged as a heterogeneous malignancy underlined by complex genetic, metabolic, and immune dysregulation. In particular, molecular studies have revealed distinct oncogenic mechanisms that have been exploited and studied as therapeutic intervention targets. These include hypoxia-driven signaling, chromosomal translocations, and gene fusion events that affect tumor progression. This review provides a comprehensive overview of these targets and rethinks RCC management. Therapeutic concepts include the targeting of genomic fusion biology with emerging cell-based immunotherapies or targeted molecular inhibition, and orthomolecular therapeutic strategies are presented. Two clinical and pathological features are highlighted—namely, the TFE3 fusion proteins in translocation RCC and the growing role of hypoxia-inducible factor-2α (HIF-2α) inhibitors in clear-cell RCC. We also present recent data on novel immunotherapeutic approaches, including autologous hematopoietic stem and progenitor cell-based interferon-α gene therapy, as well as chimeric antigen receptor T-cell therapy. These therapies are discussed in light of their mechanistic rationale, translational potential, and existing clinical challenges due to unwanted side effects. At last, orthomolecular and natural product-based therapies are reviewed for their potential as adjunctive therapies that might be used for oxidative stress management, the targeting of tumor metabolism and immune effects, and to increase standard treatment tolerance. This review points to a multidimensional framework that might support further research and studies in precision-guided RCC management, as integrative approaches may enhance therapeutic efficacy, reduce toxicity, and support the development of personalized interventions for advanced or treatment-resistant RCC. Full article

Background/Objectives: Clear-cell renal cell carcinoma (ccRCC) represents the predominant histologic subtype of renal cancer and poses persistent diagnostic challenges, particularly in the evaluation of small renal masses, where conventional imaging and biopsy have relevant limitations. Molecular imaging targeting carbonic anhydrase IX (CAIX) has emerged as a promising non-invasive alternative. This narrative review aims to summarize the biological rationale, diagnostic performance, and potential clinical applications of [⁸⁹Zr]Zr-girentuximab positron emission tomography-computed tomography (girentuximab PET-CT) in ccRCC, as well as to discuss its current limitations and future directions. Methods: A narrative synthesis of published phase 1–3 clinical trials, post hoc analyses, and early clinical series evaluating girentuximab PET-CT was performed, focusing on diagnostic accuracy, clinical impact in localized and metastatic disease, and emerging theranostic applications. Results: The phase 3 ZIRCON trial demonstrated high diagnostic accuracy of girentuximab PET-CT for indeterminate renal masses ≤7 cm, with a sensitivity of 85% and specificity of 87%, as well as performance exceeding 96% for lesions <2 cm. Early studies suggest that this modality may influence clinical decision-making by supporting active surveillance, avoiding biopsy, and refining surgical or ablative strategies, although evidence remains limited by small cohorts and lack of long-term outcome data. Exploratory data indicate improved lesion detection in metastatic ccRCC, but the absence of systematic histopathologic confirmation restricts routine staging use. Conclusions: Girentuximab PET-CT is a highly accurate, CAIX-targeted molecular imaging technique with the potential to transform the diagnostic pathway of ccRCC. While current evidence supports its use in selected localized settings, broader clinical adoption will require prospective validation of its impact on patient outcomes and management strategies. Full article

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) involves complex interactions between immune evasion and metabolic reprogramming. This study aimed to characterize ccRCC through integrated immunometabolic profiling, develop a prognostic signature, and investigate the functional role of the key driver gene UCN using in vitro and in vivo approaches. Methods: Integrated immunometabolic profiling was performed to identify molecular subtypes and establish a prognostic gene signature. Two distinct molecular subtypes were identified, and a 9-gene Immune Metabolic Index (IMI) was constructed. The functional role of the key driver gene UCN was investigated through in vitro functional assays and in vivo xenograft models in BALB/c mice, including combination with PD-1 blockade. Results: Two molecular subtypes with significant survival differences (p < 0.001) were identified. The established IMI demonstrated high prognostic accuracy, with Area Under the Curve (AUC) values of 0.813, 0.751, and 0.779 at 1-, 3-, and 5-year intervals, respectively. UCN was identified as the highest-risk gene in the signature. Functional assays showed that UCN silencing significantly inhibited cell proliferation and migration (p < 0.05). In BALB/c mouse xenograft models, UCN silencing remodeled the tumor microenvironment by increasing CD8+ T cell infiltration and reducing regulatory T cells (p < 0.01). Furthermore, UCN knockdown significantly suppressed tumor growth and synergized with PD-1 blockade to enhance antitumor efficacy (p < 0.001). Conclusions: The IMI is a robust tool for risk stratification in ccRCC. Targeting the UCN-driven immunometabolic axis represents a promising therapeutic strategy to overcome immune resistance in ccRCC. Full article

Clear cell renal cell carcinoma (ccRCC) is characterized by marked biological heterogeneity, which limits the prognostic accuracy of conventional clinicopathological models. Increasing attention has therefore focused on identification of biomarkers that can enhance risk stratification throughout all stages of the disease. Starting from the current state of the art, this narrative review summarizes and critically appraises the evidence published over the past decade regarding prognostic biomarkers in ccRCC. The analysis is structured into four overarching domains: (i) genomic biomarkers, covering somatic alterations and transcriptomic signatures; (ii) tissue-based biomarkers, including immunohistochemical surrogates and immune microenvironment features; (iii) circulating biomarkers, such as systemic inflammation parameters and indices; and (iv) integrated predictive models, represented by emerging multi-omic approaches. Going through the broad framework of potential prognostic biomarkers, emphasis is placed on their individual and integrative value in relation to classic clinical-pathological factors and survival parameters. At the tissue level, chromosome 3p-related alterations constitute a central molecular feature of ccRCC. Among these, BAP1 loss has emerged as one of the most consistently validated indicators of aggressive tumor behavior. Disruption of the SETD2/H3K36me3 axis and immune-related biomarkers, including PD-L1 expression, have demonstrated prognostic associations in selected settings, although with variable and context-dependent performance. In the circulating compartment, plasma KIM-1 has shown prognostic relevance following nephrectomy, while postoperative detection of circulating tumor DNA (ctDNA) may identify patients at increased risk of recurrence. However, limited analytical sensitivity and methodological heterogeneity currently restrict the broader clinical applicability of ctDNA-based strategies. Systemic inflammatory indices, such as the neutrophil-to-lymphocyte ratio, show reproducible associations with outcomes but largely reflect host inflammatory status rather than tumor-specific biology. However, no single biomarker currently supports routine prognostic implementation in ccRCC. Future progress will likely depend on integrative models combining genomic, tissue-based, immune, and circulating parameters with established clinical variables. Prospective validation and clear demonstration of incremental clinical utility will be essential before such strategies can meaningfully inform therapeutic decision-making. Full article

Background/Objectives: Clear cell renal cell carcinoma is the most common subtype of kidney cancer and exhibits marked biological heterogeneity, even among tumors of the same histological grade. Although tumor grade remains a key prognostic parameter, the molecular alterations associated with tumor differentiation are not fully understood. This study aimed to evaluate grade-dependent tissue-level expression patterns of proteins involved in cellular stress response, growth regulation, stemness, and apoptosis in clear cell renal cell carcinoma. Methods: Protein expression of heat shock protein 70, insulin-like growth factor 1, octamer-binding transcription factor 4, and apoptosis-inducing factor were analyzed in human clear cell renal cell carcinoma samples and normal renal cortex. Low-grade and high-grade tumors were compared using immunofluorescence staining combined with semi-quantitative and quantitative image analysis. The proportion of positive signals and the number of positive cells were assessed across tissue compartments. In addition, publicly available transcriptomic data from The Cancer Genome Atlas kidney renal clear cell carcinoma cohort were analyzed to explore associations between gene expression levels and overall survival. Results: Distinct grade-dependent expression patterns were observed for all investigated proteins. Heat shock protein 70, insulin-like growth factor 1, and octamer-binding transcription factor 4 showed a higher expression in normal renal tissue with a progressive reduction across tumor grades. In contrast, apoptosis-inducing factor exhibited increased expression in tumor tissue, particularly in low-grade tumors, with a relative decrease in high-grade carcinomas. Stromal compartments of tumor tissue showed minimal or no expression for most markers. Transcriptomic survival analysis did not reveal significant differences in overall survival between high- and low-expression groups for any of the investigated genes. Grade-stratified transcriptomic analysis of the TCGA KIRC cohort revealed consistent patterns for HSP70 family members and OCT4, with progressive grade-dependent mRNA reduction toward higher grades, while IGF1 showed an inverse mRNA trend and AIFM1 showed a uniform reduction across all tumor grades without a clear inter-grade pattern. Conclusions: The findings demonstrate that stress response, growth-related, stemness-associated, and apoptotic proteins display distinct grade-dependent tissue-level expression patterns in clear cell renal cell carcinoma, with the expression profiles of high-grade tumors being of particular translational interest given the aggressive clinical behavior and therapeutic resistance characteristic of this disease stage. These alterations appear to reflect tumor differentiation and biological behavior rather than independent prognostic value, highlighting the complexity of molecular regulation in renal tumorigenesis. Full article

Background: Non-Wilms renal tumours (NWRTs) are rare paediatric malignancies and account for a small but clinically significant proportion of childhood renal cancers. Due to their low incidence and biological heterogeneity, outcome data are limited, and management is largely extrapolated from international collaborative protocols. No national data describing the incidence and outcomes of NWRTs in children in the Republic of Ireland (ROI) have previously been published. Objective: To determine the incidence, treatment strategies, and survival outcomes of NWRTs in children in the ROI. Methods: A retrospective cohort study was conducted of all children under 16 years of age with histologically confirmed renal tumours diagnosed and treated at Children’s Health Ireland (CHI) at Crumlin between January 2005 and December 2025. As CHI Crumlin is the single national paediatric oncology centre in the ROI, this cohort represents national case ascertainment for the study period. A total of 143 paediatric renal tumours were identified; Wilms tumours (n = 118) were excluded, leaving 25 children (17.48%) with NWRTs for analysis. No cases of bilateral renal tumours were identified. Histological subtypes included renal cell carcinoma (RCC), clear cell sarcoma of the kidney (CCSK), congenital mesoblastic nephroma (CMN), malignant rhabdoid tumour of the kidney (MRTK), and anaplastic sarcoma of the kidney. Demographic characteristics, treatment strategies, and survival outcomes were analysed. Results: Twenty-five children with NWRTs were identified: CCSK (n = 9), RCC (n = 7), CMN (n = 6), MRTK (n = 2), and anaplastic sarcoma of the kidney (n = 1). At a median follow-up of 107.9 months (range 4.5–181.3 months), overall survival for the cohort was 76%. Overall survival by histology was 100% for CMN, CCSK and anaplastic sarcoma, 43% for RCC, and 0% for MRTK. Treatment strategies varied by histology, with 68% undergoing upfront surgery, 32% receiving neoadjuvant chemotherapy, 60% receiving adjuvant systemic therapy, and 44% receiving radiotherapy. Tumour recurrence occurred in 4/25 patients (16%), confined to the RCC (3) and CMN (1) subgroups. Seven Event-Free Survival events were observed, comprising three RCC relapses and one RCC progression, one CMN relapse, and two MRTK progression-related deaths. No recurrences occurred in CCSK. Conclusions: NWRTs comprised 17.5% of all paediatric renal tumours diagnosed nationally during the study period and demonstrated marked heterogeneity in outcomes according to histological subtype. CMN showed excellent survival with six out of seven requiring surgery alone, whereas MRTK remained associated with dismal outcomes despite multimodal therapy. These national data support histology-driven, risk-adapted management and highlight the importance of continued international collaboration to improve outcomes in NWRTs. Full article

Background/Objectives: Although certain established prognostic factors may occasionally fail to provide precise risk prediction in renal cell carcinoma (RCC), valosin-containing protein (VCP)/p97 has been implicated in a poor prognosis in various cancers, while its prognostic value in clear cell renal cell carcinoma (ccRCC) remains unknown. This study aimed to determine the independent prognostic value of VCP/p97 expression in ccRCC. Methods: This retrospective study included 137 ccRCC patients, and VCP/p97 expression was analyzed by immunohistochemistry and classified into either low or high expression based on the intensity of the staining in relation to the expression in endothelial cells. Results: High expression of VCP/p97 was significantly correlated with large tumor size (p < 0.001), Fuhrman nuclear grade (p = 0.003), advanced TNM stage (p < 0.001), and distant metastasis (p < 0.001). Kaplan–Meier analysis showed that the survival of patients with high expression of VCP/p97 was significantly reduced, and multivariate analysis revealed that high expression of VCP/p97 independently predicted poor survival (HR 2.09, 95% CI 1.06–4.15, p = 0.034) in addition to age, Fuhrman grade, and TNM stage. Conclusions: This study demonstrated that VCP/p97 expression, a newly identified prognostic factor, independently predicted a poor prognosis in ccRCC, and its expression may be a useful tool in identifying ccRCC patients with a poor prognosis. Full article