Search Results (9)

Background/Objectives: Accurate prognostic stratification after nephrectomy for clear cell renal carcinoma (ccRCC) remains challenging. Traditional models often lack the intuitive clinical application or the ability to handle non-linear interactions between variables. We aimed to develop and internally validate a decision tree-based model to predict cancer-specific survival in patients with ccRCC following nephrectomy. Methods: We analyzed 79,526 patients with ccRCC who underwent nephrectomy from the SEER database (2012–2018). Patients were randomized into development (2/3) and validation (1/3) cohorts. A conditional inference tree was constructed to predict cancer-specific survival. Multiple imputation by chained equations was used to handle missing data. Discriminatory ability was assessed using the C-index. Net clinical benefit was evaluated with decision curve analysis. The model was evaluated using CHARMS and PROBAST. Results: A decision tree with 15 risk groups is presented, further classified into high-, intermediate-, and low-risk categories according to observed median survival. The final predictors were tumor localization, tumor grade, TNM stage, age, and sarcomatoid differentiation. The model demonstrated excellent discriminatory performance, with a C-index of 0.846 (95% CI: 0.834–0.847). PROBAST assessment showed low risk of bias and low concern regarding applicability. Conclusions: The use of decision trees provides an interpretable alternative to conventional regression-based models. Three main risk categories and 15 subgroups are proposed based on tumor localization, tumor grade, TNM stage, age, and sarcomatoid differentiation. Our model demonstrates good applicability and a low risk of bias according to PROBAST guidelines; however, external validation in independent cohorts is required prior to clinical implementation. Full article

Background/Objectives: Sarcomatoid or rhabdoid renal cell carcinoma (sRCC) represents an aggressive dedifferentiated phenotype of RCC associated with high metastatic potential. The histologic composition of metastatic lesions arising from clear cell RCC with sarcomatoid/rhabdoid differentiation (ccRCC/sRCC) and its relationship to the primary tumor remain incompletely characterized. Methods: We retrospectively reviewed patients undergoing nephrectomy for ccRCC/sRCC who had at least one resected metastatic lesion between 2013 and 2025 at a single institution. Primary and metastatic lesions were characterized by the percentage of clear cell versus sarcomatoid/rhabdoid histology. Associations between sarcomatoid/rhabdoid percentage in the primary tumor, metastatic histology, metastatic location, and overall survival were examined. Results: Twenty-six patients with 63 metastases were included. Metastatic histology demonstrated substantial heterogeneity, with 27 lesions (43%) showing pure clear cell histology, 21 (33%) mixed, and 15 (24%) pure sarcomatoid/rhabdoid. Some patients had multiple metastases with differing histology. Increasing sarcomatoid/rhabdoid percentage in the primary was associated with a higher likelihood of sarcomatoid/rhabdoid in metastases (p < 0.001). ROC analysis demonstrated primary tumor sarcomatoid/rhabdoid percentage predicted sarcomatoid/rhabdoid differentiation in metastases (AUC 0.84, 95% CI 0.73–0.95). An optimal cutoff of 10% sarcomatoid/rhabdoid differentiation predicted sarcomatoid/rhabdoid features in metastases. Metastatic histology varied by site, with lymph node metastases more frequently demonstrating clear cell morphology and visceral metastases more commonly exhibiting sarcomatoid/rhabdoid features. Conclusions: Metastases arising from ccRCC with sarcomatoid/rhabdoid differentiation exhibit marked histologic heterogeneity. These findings highlight the complex biology of ccRCC/sRCC metastasis and underscore the need for studies examining molecular drivers of metastatic heterogeneity, as well as the relationship between metastatic histology and therapeutic response. Full article

Introduction: Sarcomatoid dedifferentiation may be identified in both clear cell renal cell carcinoma (ccRCC) and non-clear cell RCC (nccRCC). Within the SEER database (2010–2021), we tested the effect of sarcomatoid dedifferentiation in first ccRCC and subsequently in nccRCC on cancer-specific mortality (CSM). Methods: Separate propensity score matching (PSM) and multivariable competing risks regression (CRR) analyses were first applied to ccRCC with vs. without sarcomatoid dedifferentiation and subsequently to nccRCC with vs. without sarcomatoid dedifferentiation. Results: Sarcomatoid dedifferentiation was present in 2496 (3.0%) of 82,146 ccRCC patients and in 501 (1.9%) of 26,584 nccRCC. In ccRCC, after 1:2 PSM, 2496 (100%) patients with sarcomatoid dedifferentiation vs. 4992 (6.2%) patients without sarcomatoid dedifferentiation were included. At 60 months, CSM was 45.7% vs. 33.6% in ccRCC patients with vs. without sarcomatoid dedifferentiation. In CRR sarcomatoid dedifferentiation independently predicted 1.6-fold higher CSM (HR 1.6, p < 0.001). In nccRCC, after 1:2 PSM 501 (100%) patients with sarcomatoid dedifferentiation vs. 1002 (3.8%) patients without sarcomatoid dedifferentiation were included. At 60 months, CSM was 41.7% vs. 28.1% in nccRCC patients with vs. without sarcomatoid dedifferentiation. In CRR sarcomatoid dedifferentiation independently predicted 2.0-fold higher CSM (HR 2.0, p < 0.001). Conclusion: Sarcomatoid dedifferentiation is invariably associated with higher CSM in both ccRCC and nccRCC. However, the detrimental effect of sarcomatoid dedifferentiation in CSM is more pronounced in nccRCC than in ccRCC. Full article

Renal cell carcinoma (RCC) is a heterogeneous disease that represents the most common type of kidney cancer. The classification of RCC is primarily based on distinct morphological and molecular characteristics, with two broad categories: clear cell RCC (ccRCC) and non-clear cell RCC (nccRCC). Clear cell RCC is the predominant subtype, representing about 70–80% of all RCC cases, while non-clear cell subtypes collectively make up the remaining 20–30%. Non-clear cell RCC encompasses many histopathological variants, each with unique biological and clinical characteristics. Additionally, any RCC subtype can undergo sarcomatoid dedifferentiation, which is associated with poor prognosis and rapid disease progression. Recent advances in molecular profiling have also led to the identification of molecularly defined variants, further highlighting the complexity of this disease. While immunotherapy has shown efficacy in some RCC variants and subpopulations, significant gaps remain in the treatment of rare subtypes. This review explores the outcomes of immunotherapy across RCC subtypes, including rare variants, and highlights opportunities for improving care through novel therapies, biomarker-driven approaches, and inclusive clinical trial designs. Full article

(1) Background: Our aim is to describe a new mixed indocyanine-non-adhesive liquid embolic agent (Onyx-18) pre-operative renal embolization technique for assisted-robotic and laparoscopic partial nephrectomy with near-infra-red fluorescence imaging. (2) Methods: Thirteen patients with biopsy-proven renal tumors underwent pre-operative mixed indocyanine–ethylene vinyl alcohol (EVOH) embolization (Green-embo) between June 2021 and August 2022. All pre-operative embolizations were performed with a super selective stop-flow technique using a balloon microcatheter to deliver an indocyanine-EVOH mixture into tertiary order arterial branch feeders and the intra-lesional vascular supply. Efficacy (evaluated as complete embolization, correct tumor mapping on infra-red fluorescence imaging and clamp-off surgery) and safety (evaluated as complication rate and functional outcomes) were primary goals. Clinical and pathological data were also collected. (3) Results: Two male and eleven female patients (mean age 72 years) received pre-operative Green-embo. The median tumor size was 29 mm (range 15–50 mm). Histopathology identified renal cell carcinoma (RCC) in 9 of the 13 (69%) patients, oncocytoma in 3 of the 13 (23%) patients and sarcomatoid RCC in 1 of the 13 (8%) patients. Lesions were equally distributed between polar, meso-renal, endo- and exophytic locations. Complete embolization was achieved in all the procedures. A correct green mapping was identified during all infra-red fluorescence imaging. All patients were discharged on the second day after the surgery. The median blood loss was 145 cc (10–300 cc). No significant differences were observed in serum creatinine levels before and after the embolization procedures. (4) Conclusions: The Green-tattoo technique based on a mixed indocyanine-non-adhesive liquid embolic agent (Onyx-18) is a safe and effective pre-operative embolization technique. The main advantages are the excellent lesion mapping for fluorescence imaging, reduction in surgical time, and definitive, complete and immediate tumor devascularization based on the deep Onyx-18 penetration, leading to a very low intra-operative blood loss. Full article

This study was carried out to quantitate the expression levels of microRNA-17, -19a, -34a, -155, and -210 (miRs) expressed in nine clear cell renal cell carcinoma (ccRCC) and one chromophobe renal cell carcinoma cell line with and without sarcomatoid differentiation, and in six primary kidney tumors with matching normal kidney tissues. The data in the five non-sarcomatoid ccRCC cell lines—RC2, CAKI-1, 786-0, RCC4, and RCC4/VHL—and in the four ccRCC with sarcomatoid differentiation—RCJ41T1, RCJ41T2, RCJ41M, and UOK-127—indicated that miR-17 and -19a were expressed at lower levels relative to miR-34a, -155, and -210. Compared with RPTEC normal epithelial cells, miR-34a, miR-155, and miR-210 were expressed at higher levels, independent of the sarcomatoid differentiation status and hypoxia-inducible factors 1α and 2α (HIFs) isoform expression. In the one chromophobe renal cell carcinoma cell line, namely, UOK-276 with sarcomatoid differentiation, and expressing tumor suppressor gene TP53, miR-34a, which is a tumor suppressor gene, was expressed at higher levels than miR-210, -155, -17, and -19a. The pilot results generated in six tumor biopsies with matching normal kidney tissues indicated that while the expression of miR-17 and -19a were similar to the normal tissue expression profile, miR-210, -155, -and 34a were expressed at a higher level. To confirm that differences in the expression levels of the five miRs in the six tumor biopsies were statistically significant, the acquisition of a larger sample size is required. Data previously generated in ccRCC cell lines demonstrating that miR-210, miR-155, and HIFs are druggable targets using a defined dose and schedule of selenium-containing molecules support the concept that simultaneous and concurrent downregulation of miR-210, miR-155, and HIFs, which regulate target genes associated with increased tumor angiogenesis and drug resistance, may offer the potential for the development of a novel mechanism-based strategy for the treatment of patients with advanced ccRCC. Full article

Loss of the polybromo-1 (PBRM1) protein has been expected as a possible biomarker for clear cell renal cell carcinoma (ccRCC). There is little knowledge about how PBRM1 immunohistochemical expression correlates with the histomorphological features of ccRCC and the endothelial expression of tumor vasculature. The present study evaluates the association of architectural patterns with the PBRM1 expression of cancer cells using a cohort of 425 patients with nonmetastatic ccRCC. Furthermore, we separately assessed the PBRM1 expression of the endothelial cells and evaluated the correlation between the expression of cancer cells and endothelial cells. PBRM1 loss in cancer cells was observed in 148 (34.8%) patients. In the correlation analysis between architectural patterns and PBRM1 expression, macrocyst/microcystic, tubular/acinar, and compact/small nested were positively correlated with PBRM1 expression, whereas alveolar/large nested, thick trabecular/insular, papillary/pseudopapillary, solid sheets, and sarcomatoid/rhabdoid were negatively correlated with PBRM1 expression. PBRM1 expression in vascular endothelial cells correlated with the expression of cancer cells (correlation coefficient = 0.834, p < 0.001). PBRM1 loss in both cancer and endothelial cells was associated with a lower recurrence-free survival rate (p < 0.001). Our PBRM1 expression profile indicated that PBRM1 expression in both cancer and endothelial cells may be regulated in an orchestrated manner. Full article

Purpose: Although mutations are associated with carcinogenesis, little is known about survival-specific genes in clear cell renal cell carcinoma (ccRCC). We developed a customized next-generation sequencing (NGS) gene panel with 156 genes. The purpose of this study was to investigate whether the survival-specific genes we found were present in Korean ccRCC patients, and their association with clinicopathological findings. Materials and Methods: DNA was extracted from the formalin-fixed, paraffin-embedded tissue of 22 ccRCC patients. NGS was performed using our survival-specific gene panel with an Illumina MiSeq. We analyzed NGS data and the correlations between mutations and clinicopathological findings and also compared them with data from the Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) and Renal Cell Cancer-European Union (RECA-EU). Results: We found a total of 100 mutations in 37 of the 156 genes (23.7%) in 22 ccRCC patients. Of the 37 mutated genes, 11 were identified as clinicopathologically significant. Six were novel survival-specific genes (ADAMTS10, CARD6, NLRP2, OBSCN, SECISBP2L, and USP40), and five were top-ranked mutated genes (AKAP9, ARID1A, BAP1, KDM5C, and SETD2). Only CARD6 was validated as an overall survival-specific gene in this Korean study (p = 0.04, r = −0.441), TCGA-KIRC cohort (p = 0.0003), RECA-EU (p = 0.0005). The 10 remaining gene mutations were associated with clinicopathological findings; disease-free survival, mortality, nuclear grade, sarcomatoid component, N-stage, sex, and tumor size. Conclusions: We discovered 11 survival-specific genes in ccRCC using data from TCGA-KIRC, RECA-EU, and Korean patients. We are the first to find a correlation between CARD6 and overall survival in ccRCC. The 11 genes, including CARD6, NLRP2, OBSCN, and USP40, could be useful diagnostic, prognostic, and therapeutic markers in ccRCC. Full article

In renal cell carcinoma (RCC), single members of the Wnt/β-catenin signaling cascade were recently identified to contribute to cancer progression. However, the role of Wnt1, one of the key ligands in β-catenin regulation, is currently unknown in RCC. Therefore, alterations of the Wnt1/β-catenin axis in clear cell RCC (ccRCC) were examined with regard to clinicopathology, overall survival (OS) and cancer specific survival (CSS). Corresponding ccRCCs and benign renal tissue were analyzed in 278 patients for Wnt1 and β-catenin expression by immunohistochemistry in tissue microarrays. Expression scores, including intensity and percentage of stained cells, were compared between normal kidney and ccRCCs. Data was categorized according to mean expression scores and correlated to tumor and patients’ characteristics. Survival was analyzed according to the Kaplan-Meier and log-rank test. Univariable and multivariable Cox proportional hazard regression models were used to explore the independent prognostic value of Wnt1 and β-catenin. In ccRCCs, high Wnt1 was associated with increased tumor diameter, stage and vascular invasion (p ≤ 0.02). High membranous β-catenin was associated with advanced stage, vascular invasion and tumor necrosis (p ≤ 0.01). Higher diameter, stage, node involvement, grade, vascular invasion and sarcomatoid differentiation (p ≤ 0.01) were found in patients with high cytoplasmic β-catenin. Patients with a high cytoplasmic β-catenin had a significantly reduced OS (hazard ratio (HR) 1.75) and CSS (HR 2.26), which was not independently associated with OS and CSS after adjustment in the multivariable model. Increased ccRCC aggressiveness was reflected by an altered Wnt1/β-catenin signaling. Cytoplasmic β-catenin was identified as the most promising candidate associated with unfavorable clinicopathology and impaired survival. Nevertheless, the shift of membranous β-catenin to the cytoplasm with a subsequently increased nuclear expression, as shown for other malignancies, could not be demonstrated to be present in ccRCC. Full article