Search Results (81)

(1) Background: Sertoli–Leydig cell tumors (SLCTs) are rare ovarian neoplasms that account for less than 0.5% of all ovarian tumors. They usually affect young women and often present with androgenic symptoms. We report a unique case of a 40-year-old woman diagnosed with both SLCT and clear cell papillary renal cell carcinoma (CCP-RCC), a rare tumor association with unclear pathogenesis. (2) Methods: Both tumors were treated surgically. The diagnostic workup included hormonal testing, imaging studies, and extensive genetic testing, including DICER1 mutation analysis and multiplex ligation-dependent probe amplification (MLPA), as well as the examination of a next-generation sequencing (NGS) panel covering ~280 cancer-related genes. (3) Results: Histopathologic examination confirmed a well-differentiated SLCT and CCP-RCC. No pathogenic variants in DICER1 were identified by WES or MLPA. No clinically relevant changes were found in the extended NGS panel either, so a known hereditary predisposition could be ruled out. The synchronous occurrence of both tumors without genomic alterations could indicate a sporadic event or as yet unidentified mechanisms. (4) Conclusions: This case highlights the importance of a multidisciplinary approach in the management of rare tumor compounds. The exclusion of DICER1 mutations and the absence of genetic findings adds new evidence to the limited literature and underscores the importance of long-term surveillance and further research into potential shared oncogenic pathways. Full article

Objectives: The aim of the study was to assess the utility of contrast-enhanced ultrasound (CEUS), using both qualitative and quantitative perfusion analysis, in differentiating subtypes of renal cell carcinoma (RCC). Methods: This prospective, single-center study includes 91 patients with histologically confirmed RCC. We performed a CEUS within one week prior to nephrectomy. Qualitative parameters (enhancement pattern, heterogeneity, pseudocapsule) and quantitative perfusion metrics were assessed. Logistic regression models were developed to evaluate the diagnostic performance of CEUS in differentiating high-grade (clear cell RCC) from low-grade RCC (papillary and chromophobe). Results: Qualitative CEUS findings showed that hyperenhancement and isoenhancement were significantly associated with high-grade RCC (OR = 38.3 and OR = 7.8, respectively; p < 0.001 and p = 0.014). Hypoenhancement was predominant in low-grade RCC (80.0%). Quantitative parameters, including peak enhancement and wash-in/wash-out area under the curve, significantly differed between tumor grades (p < 0.001). A model using qualitative parameters alone achieved an AUC of 0.847 and 81.9% accuracy. Adding quantitative metrics marginally improved performance (AUC 0.912, accuracy 86.2%), though not significantly. Conclusions: CEUS provides valuable diagnostic information in differentiating RCC subtypes, with qualitative parameters alone demonstrating strong predictive power. While quantitative analysis slightly enhances diagnostic accuracy, its added value may be limited by technical challenges. Full article

Background/Objectives: Kidney transplantation is associated with an increased risk of renal cell carcinoma (RCC). This study aimed to evaluate the outcomes of de novo RCC in kidney transplant recipients (KTRs). Methods: We retrospectively identified 50 de novo RCC cases among 4012 KTRs transplanted from 2005 to 2024. Data on patient characteristics and outcomes were collected. Propensity score matching (PSM) compared 34 localized RCC cases in KTRs with 34 non-transplant RCC cases. The statistical analyses used Kaplan–Meier estimates, the log-rank test, and the Cox regression. Results: The RCC incidence was 0.64 per 1000 person-years, with a standardized incidence ratio of 4.40 (95% CI: 3.33–5.80). In the KTR cohort, clear cell RCC was present in 42%, and papillary RCC was present in 42%. RCC developed predominantly in native kidneys (92%). UICC stage I was present in 74%. The treatment for the non-metastatic RCC was nephrectomy in the majority of cases (91%). For the metastatic RCC, 71% received a tyrosine kinase inhibitor (TKI). In the KTR cohort, the 3- and 5-year overall survival (OS) rates were 85% and 72%, respectively, with a median OS of 199 months; the synchronous metastasized (M1) patients had a median OS of 14 months. Rejection, age, advanced UICC stage, higher pT stage, clinical positive lymph nodes, M1, and higher grade were significantly associated with poor OS. The 5-year OS (96% vs. 84%, p = 0.72) and MFS (92% vs. 93%, p = 0.61) were comparable in the PSM cohort between the KTRs and the non-KTRs in the localized RCC. Conclusions: KTRs have a higher risk of RCC and present at a localized stage with comparable OS rates to non-transplant RCC patients. Adverse tumor characteristics, including synchronous metastases, significantly affect the prognosis, highlighting the need for surveillance and individualized treatment, particularly for metastatic RCC. Full article

Currently, there is no standard treatment for renal cell carcinoma (RCC) that is free of side effects and resistance. Additionally, limited information exists on how curcumin affects the gene expression profiles of patients with translocation renal cell carcinoma (tRCC) and papillary renal cell carcinoma (pRCC). The pathways responsible for metastasis in tRCC are still not well understood, and there is no established treatment or reliable biomarker to predict outcomes for metastatic tRCC. Primary clinical data from patients were retrieved from the TCGA database and analyzed using cBioPortal, stitch, string, R and Python. Various analyses were performed, including differential gene expression, protein-protein interaction (PPI) network analysis, drug-targeted gene analysis, gene ontology (GO), enrichment analyses, and systematic searches to assess the impact of curcumin on the transcriptomic profiles of tRCC, pRCC, and clear cell renal cell carcinoma (ccRCC). No significant impact of sensitive genes on survival in KIRC and KIRP was found, though a trend suggested they may delay disease progression. The combination of curcumin with sunitinib showed promise in overcoming drug resistance in ccRCC by inducing ferroptosis, reducing iron, and increasing ADAMTS18 expression. This study, leveraging data from the TCGA database and other databases explored the impact of curcumin on transcriptomic profiles in tRCC, pRCC, and clear cell RCC (ccRCC). Gene analysis revealed immune and metabolic differences, with KIRC showing a stronger immune response. This study is the first to propose that future research into the miR-148/ADAMTS18 genes and the ferroptosis pathway in tRCC and pRCC could lead to the development of new therapies and the identification of novel therapeutic targets, potentially overcoming drug resistance and metastasis. Full article

Non-clear cell renal cell carcinoma (nccRCC) represents a heterogenous group of malignancies with varying degrees of clinical aggressiveness and response to different systemic therapies. As the characterization of subtypes of nccRCC continues to evolve, it is important to understand the evidence around systemic treatments used in advanced or metastatic stages of specific subtypes. Here, we review the literature on systemic therapies in nccRCC, with a focus on prospective trials that included patients with papillary renal cell carcinoma (RCC), chromophobe RCC, RCC not further classified/unclassified RCC, translocation RCC, collecting duct RCC, and renal medullary carcinoma. We also review emerging treatments for other molecularly defined subtypes of this disease. Full article

Background/Objectives: RNA-modifying proteins play a crucial role in the progression of cancer. The fat mass and obesity-associated protein (FTO) and alkB homolog 5 RNA demethylase (ALKBH5) are RNA-demethylating proteins that have contrasting effects in renal cell carcinoma (RCC) among different populations. This research investigates the genotype and expression levels of FTO and ALKBH5 in RCC patients from the Middle East and Northern Africa (MENA) region. Methods: Formalin-fixed paraffin-embedded samples from the kidney biopsies of RCC patients and controls were examined using targeted DNA sequencing, whole transcriptome profiling, and immunohistochemistry. Results: Our findings show that the rs11075995T variant in FTO is associated with a heightened risk of clear-cell RCC (ccRCC). ALKBH5 and FTO protein expression were significantly lower in ccRCC and chromophobe RCC (chRCC) patients but not in papillary RCC (pRCC) patients. In ccRCC, transcriptomic data revealed a significant downregulation of FTO (log₂FC = −5.2, q < 0.001) and ALKBH5 (log₂FC = −4.7, q < 0.001) compared to controls. A significant negative correlation was found in ccRCC between FTO expression and T allele frequency in rs11075995, suggesting that FTO expression is affected. Conclusions: This is the first demonstration of the association of the dysregulated expression of FTO and ALKBH5 in ccRCC and chRCC patients from the MENA region. FTO variant rs11075995T increased the risk of ccRCC and was negatively associated with FTO protein expression. Full article

Background and Objective. The significance of microRNAs (miRNAs) in relation to neoplastic diseases; such as renal carcinoma carcinoma (RCC); has been brought to light by recent studies. Analyzing the main urinary miRNAs implicated in RCC and their potential diagnostic use was the goal of this systematic review of the literature. Methods. This systematic review was performed following the PROSPERO protocol CRD42024550716. Our literature search strategies were deciding which database to include (Pubmed; EMBASE and Clinicaltrial.gov) and composing strings with words related to urinary miRNA in patients with RCC. Key findings and limitations. After screening; 10 papers were included from the 593 records that the systematic review found. No miRNA was investigated in more than one paper by different authors. The miR-210 and let-7 family were the most investigated and resulted upregulated in RCC cases compared to controls. Five papers reported different expression of miRNAs in urine samples before and after surgery: miR-15a; miR-34a-5p; miR-200a-3p; miR-205-5p; miR-210; miR-210-3p; miR-365a-3p and let-7d-5p levels decreased after nephrectomy. Meta-analysis was not performed since the included studies were heterogeneous; in terms of studied miRNA; of the normalizer used during stabilization phase; and histologic type of RCC (clear cell RCC; papillary RCC; unspecified RCC). Conclusions. Considering the variability and heterogeneity of the obtained results; as well as the vastness of the topic; expanding research in this field appears highly promising. To support further advancements; it would be useful to establish a database that consolidates international findings. 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

Background/Objectives: Renal cell carcinoma is an aggressive form of kidney cancer, contributing to an estimated 138,000 deaths globally in 2017. Traditional treatments like chemotherapy and radiation are generally considered ineffective. Additionally, CD47 has been identified as a crucial tumor antigen involved in the development and progression of various cancers, including renal cell carcinoma. The interaction of CD47 with SIRPα triggers a “don’t eat me” signal to the macrophages, inhibiting phagocytosis. Much progress has been made in targeting CD47 for cancer immunotherapy in solid tumors (STs) and hematological malignancies. This study aimed to evaluate CD47 expression in malignant and benign renal cell tumors and compare it with prognostic histopathological parameters. Methods: We included 160 malignant and 26 benign tumors. The malignant tumors consisted of renal cell carcinoma (RCC) subtypes including 37 clear cell, 30 chromophobe, 30 papillary type 1, 29 papillary type 2, and 34 unclassified RCC cases. As for the benign tumors, we included 26 oncocytoma cases. All samples were stained with anti-CD47 antibodies by immunohistochemistry methods. Results: The statistical analysis yielded a significant correlation between CD47 expression and survival, metastasis, and capsule invasion for the unclassified RCC cases. We did not find any further significant correlation between CD47 expression and the studied parameters. Conclusions: To the best of our knowledge, our study is the first to research CD47 expression in benign and malignant renal carcinoma subtypes. Further large-scale studies are needed to determine the expression profile of CD47 in renal cell tumors. Full article

Background: Renal cell carcinoma (RCC) is a highly aggressive malignancy accounting for the majority of kidney cancers. Despite recent advancements in therapeutic options, the prognosis for advanced-stage RCC remains poor. Niemann–Pick C1-Like 1 (NPC1L1) plays a crucial role in cholesterol absorption and has been implicated in cancer progression across various cancers. However, its expression patterns and prognostic significance in RCC remain unclear. Methods: In this study, NPC1L1 expression in normal and RCC tissues, including subtypes, was compared using TCGA, GEPIA2, and The Human Protein Atlas. Clinical correlations were assessed, and the impact of NPC1L1 on overall survival (OS) and progression-free survival (PFS) was evaluated. Gene effect scores were analyzed using the DepMap tool to determine the involvement of NPC1L1 in RCC progression. Results: NPC1L1 expression was significantly lower in RCC tissues compared to normal tissues, particularly in the clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC) subtypes, but increased in advanced tumor stages. Higher NPC1L1 expression was associated with worse OS and PFS in RCC patients. Multivariable Cox regression confirmed NPC1L1 as an independent prognostic marker. Additionally, gene effect scores showed that NPC1L1 is essential for the survival of specific RCC cell lines. Conclusions: This study determines NPC1L1 as an independent prognostic indicator in RCC, with higher expression associated with poor survival outcomes. These findings suggest that NPC1L1 could serve as a valuable marker for identifying high-risk RCC patients. Further research is required to investigate the molecular mechanisms underlying the role of NPC1L1 in RCC progression. Full article

We investigated the mRNA expression of 124 cuproptosis-associated genes in 7489 biopsies from 20 different tumor types of The Cancer Genome Atlas (TCGA). The KM plotter algorithm has been used to calculate Kaplan–Meier statistics and false discovery rate (FDR) corrections. Interaction networks have been generated using Ingenuity Pathway Analysis (IPA). High mRNA expression of 63 out of 124 genes significantly correlated with shorter survival times of cancer patients across all 20 tumor types. IPA analyses revealed that their gene products were interconnected in canonical pathways (e.g., cancer, cell death, cell cycle, cell signaling). Four tumor entities showed a higher accumulation of genes than the other cancer types, i.e., renal clear cell carcinoma (n = 21), renal papillary carcinoma (n = 13), kidney hepatocellular carcinoma (n = 13), and lung adenocarcinoma (n = 9). These gene clusters may serve as prognostic signatures for patient survival. These signatures were also of prognostic value for tumors with high mutational rates and neoantigen loads. Cuproptosis is of prognostic significance for the survival of cancer patients. The identification of specific gene signatures deserves further exploration for their clinical utility in routine diagnostics. Full article

Kidney cancer is a malignant tumor with a high mortality rate. The accurate segmentation of tumors from computed tomography (CT) scans can assist physicians in clinical diagnosis. We introduced a new segmentation network called DWR-SegFormer to address the challenge of accurately segmenting kidney tumors in CT images. The method involved binarizing the label maps of clear cell renal cell carcinoma and papillary renal cell carcinoma CT images for identification, and the cancer lesion area was obtained by the label so that the model could accurately identify the area and enhance the feature extraction ability. Secondly, an optimized segmentation model combining a DWR attention mechanism and SegFormer network was constructed. MiT-B0 was used as the encoder of the model to establish long-distance feature dependencies and effectively extract feature information at different resolutions. The decoder with a multi-branch DWR module was implemented to utilize multi-scale feature information effectively and enhance segmentation accuracy. Comparing the experimental results with other existing models shows that the model significantly outperformed the comparison methods in all evaluation metrics on the CT image dataset of clear cell renal cancer. Furthermore, the experimental findings highlight the robustness of the proposed model across other datasets. Full article

Stimulator of interferon genes protein (STING) activates the immune response in inflammatory cells. STING expression in cancer cells is less well characterized, but STING agonists are currently being evaluated as anticancer drugs. A tissue microarray containing 18,001 samples from 139 different tumor types was analyzed for STING by immunohistochemistry. STING-positive tumor cells were found in 130 (93.5%) of 139 tumor entities. The highest STING positivity rates occurred in squamous cell carcinomas (up to 96%); malignant mesothelioma (88.5%–95.7%); adenocarcinoma of the pancreas (94.9%), lung (90.3%), cervix (90.0%), colorectum (75.2%), and gallbladder (68.8%); and serous high-grade ovarian cancer (86.0%). High STING expression was linked to adverse phenotypes in breast cancer, clear cell renal cell carcinoma, colorectal adenocarcinoma, hepatocellular carcinoma, and papillary carcinoma of the thyroid (p < 0.05). In pTa urothelial carcinomas, STING expression was associated with low-grade carcinoma (p = 0.0002). Across all tumors, STING expression paralleled PD-L1 positivity of tumor and inflammatory cells (p < 0.0001 each) but was unrelated to the density of CD8+ lymphocytes. STING expression is variable across tumor types and may be related to aggressive tumor phenotype and PD-L1 positivity. The lack of relationship with tumor-infiltrating CD8+ lymphocytes argues against a significant IFN production by STING positive tumor cells. Full article

Renal cell carcinoma (RCC) is a significant oncological challenge due to its heterogeneous nature and limited treatment options. The PAX developmental gene family encodes nine highly conserved transcription factors that play crucial roles in embryonic development and organogenesis, which have been implicated in the occurrence and development of RCC. This review explores the molecular landscape of RCC, with a specific focus on the role of the PAX gene family in RCC tumorigenesis and disease progression. Of the various RCC subtypes, clear cell renal cell carcinoma (ccRCC) is the most prevalent, characterized by the loss of the von Hippel–Lindau (VHL) tumor suppressor gene. Here, we review the published literature on the expression patterns and functional implications of PAX genes, particularly PAX2 and PAX8, in the three most common RCC subtypes, including ccRCC, papillary RCC (PRCC), and chromophobe RCC (ChRCC). Further, we review the interactions and potential biological mechanisms involving PAX genes and VHL loss in driving the pathogenesis of RCC, including the key signaling pathways mediated by VHL in ccRCC and associated mechanisms implicating PAX. Lastly, concurrent with our update regarding PAX gene research in RCC, we review and comment on the targeting of PAX towards the development of novel RCC therapies. Full article

This review highlights recent advances in renal cell carcinoma (RCC) imaging. It begins with dual-energy computed tomography (DECT), which has demonstrated a high diagnostic accuracy in the evaluation of renal masses. Several studies have suggested the potential benefits of iodine quantification, particularly for distinguishing low-attenuation, true enhancing solid masses from hyperdense cysts. By determining whether or not a renal mass is present, DECT could avoid the need for additional imaging studies, thereby reducing healthcare costs. DECT can also provide virtual unenhanced images, helping to reduce radiation exposure. The review then provides an update focusing on the advantages of multiparametric magnetic resonance (MR) imaging performance in the histological subtyping of RCC and in the differentiation of benign from malignant renal masses. A proposed standardized stepwise reading of images helps to identify clear cell RCC and papillary RCC with a high accuracy. Contrast-enhanced ultrasound may represent a promising diagnostic tool for the characterization of solid and cystic renal masses. Several combined pharmaceutical imaging strategies using both sestamibi and PSMA offer new opportunities in the diagnosis and staging of RCC, but their role in risk stratification needs to be evaluated. Although radiomics and tumor texture analysis are hampered by poor reproducibility and need standardization, they show promise in identifying new biomarkers for predicting tumor histology, clinical outcomes, overall survival, and the response to therapy. They have a wide range of potential applications but are still in the research phase. Artificial intelligence (AI) has shown encouraging results in tumor classification, grade, and prognosis. It is expected to play an important role in assessing the treatment response and advancing personalized medicine. The review then focuses on recently updated algorithms and guidelines. The Bosniak classification version 2019 incorporates MRI, precisely defines previously vague imaging terms, and allows a greater proportion of masses to be placed in lower-risk classes. Recent studies have reported an improved specificity of the higher-risk categories and better inter-reader agreement. The clear cell likelihood score, which adds standardization to the characterization of solid renal masses on MRI, has been validated in recent studies with high interobserver agreement. Finally, the review discusses the key imaging implications of the 2017 AUA guidelines for renal masses and localized renal cancer. Full article