William Wang, Tarek Zaho, Allen Cao, Gopal H Badlani, Soroush Rais-Bahrami, Anthony Atala, Yuanyuan Zhang
{"title":"Regenerative strategies for post-prostatectomy incontinence: stem cells, exosomes, and the path to clinical resolution.","authors":"William Wang, Tarek Zaho, Allen Cao, Gopal H Badlani, Soroush Rais-Bahrami, Anthony Atala, Yuanyuan Zhang","doi":"10.62347/MBLA4964","DOIUrl":"10.62347/MBLA4964","url":null,"abstract":"<p><p>Radical prostatectomy (RP) is a highly effective treatment for localized prostate cancer; unfortunately, post-prostatectomy urinary incontinence (UI) remains a prevalent and distressing complication, significantly diminishing patients' quality of life. Current therapeutic options often provide incomplete continence restoration and may lead to substantial morbidity. This review examines the rapidly advancing field of regenerative medicine, specifically focusing on stem cell and exosome-based therapies as innovative approaches to address post-RP UI. We go deeper into the unique pathophysiology of male post-prostatectomy UI, distinguishing it from other forms of UI, and present the compelling biological rationale for these regenerative interventions. Highlighting advancements from 2014 to 2025, we explore recent preclinical and clinical progress in this domain. Furthermore, we critically assess the persistent challenges crucial for widespread clinical application, including optimizing cell dose and source, ensuring long-term efficacy and safety, and interpreting complex regulatory environments. By bridging the understanding of sex-related differences between females and males in UI and tackling the specific challenges of male post-RP incontinence, this review emphasizes that while promising, the journey from laboratory bench to bedside for these innovative therapies demands rigorous scientific inquiry and collaborative efforts.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"14 1","pages":"17-33"},"PeriodicalIF":1.4,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuyan Yang, Yijiang Song, Pinning Feng, Xianlian Deng, Ya Li, Peijia Liu, Bin Peng, Yuanrui Liu, Youlin Liu, Jin Li, Peng Zhang, Feng Hu
{"title":"A non-invasive predictive model for identifying non-diabetic kidney disease in type 2 diabetes mellitus: development and multicenter validation.","authors":"Yuyan Yang, Yijiang Song, Pinning Feng, Xianlian Deng, Ya Li, Peijia Liu, Bin Peng, Yuanrui Liu, Youlin Liu, Jin Li, Peng Zhang, Feng Hu","doi":"10.62347/UYEP2269","DOIUrl":"10.62347/UYEP2269","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to develop a non-invasive, simple, and rapid predictive model for identifying non-diabetic kidney disease (NDKD) in patients with type 2 diabetes mellitus (T2DM).</p><p><strong>Methods: </strong>We performed a retrospective analysis of clinical data from 117 T2DM patients who underwent renal biopsy at a single medical institution between 2017 and 2022; candidate variables were first prioritized based on clinical relevance, followed by the construction of a predictive framework using logistic regression. Dubbed the RICH model, the final framework integrated four key parameters: red blood cell (RBC) count, immunoglobulin A (IgA) level, cystatin C-derived estimated glomerular filtration rate (eGFR_2), and glycated hemoglobin A1c (HbA1c).</p><p><strong>Results: </strong>External validation was conducted across three independent centers involving 299 T2DM patients (2018-2024), achieving area under the receiver operating characteristic curve (AUC-ROC) values of 0.755, 0.764, and 0.755, which complemented the internal validation AUC-ROC of 0.847; at an optimal threshold probability of 0.559, approximately 20% of patients obtained clinical net benefit from the model, and notably, applying the RICH model for early NDKD screening has the potential to reduce the renal biopsy rate by 42.05%.</p><p><strong>Conclusions: </strong>The RICH model exhibits robust performance in predicting NDKD among T2DM patients with renal impairment, providing a practical tool for clinical decision-making.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"14 1","pages":"1-16"},"PeriodicalIF":1.4,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jojo Maier, Elliot Heye, Monica Ridlon, Marcela Ambrogi, Douglas W Strand, Kimberly P Keil-Stietz, Chad M Vezina
{"title":"Peripheral serotonin contributes to testosterone and estradiol induced urinary voiding dysfunction in adult male mice.","authors":"Jojo Maier, Elliot Heye, Monica Ridlon, Marcela Ambrogi, Douglas W Strand, Kimberly P Keil-Stietz, Chad M Vezina","doi":"10.62347/QDWM4583","DOIUrl":"10.62347/QDWM4583","url":null,"abstract":"<p><strong>Objective: </strong>Millions of aging men are diagnosed with lower urinary tract dysfunction (LUTD) each year. Alpha adrenergic receptor blockers relax prostatic, urethral, and bladder smooth muscle to relieve LUTD symptoms and are often, but not always, effective. Serotonin is proposed to cause contractions in the female urethra, as well as in the lungs and bowel. This study tests that serotonin synthesized in the periphery, outside of the central nervous system, contributes to the development of LUTD induced in mice by subcutaneous implants of testosterone (T) and estradiol (E2), mimicking the hormone milieu of aging men.</p><p><strong>Methods: </strong>Immunofluorescent staining of male human and mouse urethra was used to confirm the presence of neuroendocrine cells and interstitial cells of Cajal, which contribute to serotonin-induced contractions in the female mouse urethra. Wild type and tryptophan hydroxylase 1 null (<i>Tph1<sup>-/-</sup></i> ) mice, which are deficient in the rate-limiting enzyme in peripheral serotonin synthesis, were given sham surgery or T+E2 implants. Voiding behavior was measured with the void spot assay one day before surgery and two weeks post-surgery. Four weeks after surgery, bladders were exteriorized and measured to calculate volume, and anesthetized cystometry was performed to assess bladder activity.</p><p><strong>Results: </strong>Serotonin-positive neuroendocrine cells and serotonin receptor positive interstitial cells of Cajal were detected in the prostatic urethra of humans and mice. Two weeks after T+E2 implantation surgery, a baseline level of urinary retention occurred in both wild type and <i>Tph1<sup>-/-</sup></i> mice. However, wild type mice treated with T+E2 had increased frequent small voids (P<0.01) and decreased bladder activity (P<0.005) when compared to wild type mice with sham treatment and <i>Tph1<sup>-/-</sup></i> mice with T+E2 treatment.</p><p><strong>Conclusions: </strong>Wild type mice developed a more severe voiding dysfunction phenotype than <i>Tph1<sup>-/-</sup></i> mice when treated with T+E2, indicating that peripheral serotonin plays a role in T+E2-mediated LUTD. Because the urinary dysfunction observed in mice mimics that of human men, future studies to understand and exploit the role of serotonin may provide a treatment option for a subset of LUTD.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"14 1","pages":"34-44"},"PeriodicalIF":1.4,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147497261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The associations between volatile organic compounds exposure and urine flow rate in US adults: NHANES 2011-2020.","authors":"Xiudeng Yang, Zhixue Zhang","doi":"10.62347/PVEJ3423","DOIUrl":"10.62347/PVEJ3423","url":null,"abstract":"<p><strong>Objective: </strong>Metabolites of volatile organic compounds (mVOCs) have attracted considerable attention in contemporary research. The urine flow rate (UFR) serves as an objective metric for a full evaluation of bladder function. This research aimed to investigate the correlation between mVOCs and UFR.</p><p><strong>Methods: </strong>We examined mVOCs and UFR data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2020. The mVOCs measurements were subjected to log transformation to achieve normal distribution. We used weighted multivariate linear regression models to evaluate the association between mVOCs andUFR. The relationship between mVOCs mixture and UFR was assessed using three different analytical models: Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS), and quantile g-computation (Qgcomp). An analysis stratified by gender was also conducted.</p><p><strong>Results: </strong>The research had 3,370 participants, of whom 1,703 (51%) were male. Multivariate linear regression revealed a negative correlation between increased mVOCs and UFR across all research cohorts (all <i>P</i> < 0.001). The BKMR model displayed a notable negative correlation, identifying N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA) and Phenylglyoxylic acid (PGA) as possibly important chemicals. The WQS model exhibited a negative connection with UFR across the total cohort and its male and female subgroups, with all <i>P</i> values being less than 0.05. The findings of the Qgcomp model aligned with those of the WQS model.</p><p><strong>Conclusions: </strong>Our data indicate a substantial negative connection between exposure to urinary mVOCs and UFR among US adults, with no notable gender differences seen.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"13 6","pages":"377-389"},"PeriodicalIF":1.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mechanisms of prostatic inflammation-mediated male lower urinary tract symptoms.","authors":"Brandon R Scharpf, Chad M Vezina","doi":"10.62347/ATKI4166","DOIUrl":"10.62347/ATKI4166","url":null,"abstract":"<p><p>Lower urinary tract dysfunction (LUTD) is prevalent in aging men. It is characterized by urinary symptoms such as weak stream and more frequent urination, and is linked to a variety of prostate and urethral pathologies. While the leading medical therapies for male LUTD aim to reduce the tone and volume of the prostate and urethra, no current therapies target two prominent emerging mechanisms of male LUTD: prostate inflammation and fibrosis. LUTD arises and progresses over decades of a man's life, making it difficult to pinpoint disease mechanisms. Non-human research models, including mice, have been useful for investigating slow-progressing diseases of aging. Research involving mouse models of lower urinary tract dysfunction is surging due to a growing suite of genetic, pharmacological and immune-based tools for manipulating mouse prostate histopathology, cell signaling and phenotyping mouse urinary voiding. Current research is focused on understanding how macrophages, fibrocytes, mast cells and other cells are recruited to the prostate and how these cells are activated to drive prostate inflammation and fibrosis. This review highlights recent mouse studies to investigate the cellular and molecular underpinnings of prostate inflammation and fibrosis, and the molecular mechanisms that have emerged from these studies as potential therapeutic targets.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"13 6","pages":"360-376"},"PeriodicalIF":1.4,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12816821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pengfei Yu, Jiaqi Li, Huifen Ding, Yu Chen, Carol C Christina, Anthony Bleyer, Zhongping Duan, Anthony Atala, Yuanyuan Zhang
{"title":"Urine-derived stem cells as a model for age-related kidney degeneration and chronic disease risk.","authors":"Pengfei Yu, Jiaqi Li, Huifen Ding, Yu Chen, Carol C Christina, Anthony Bleyer, Zhongping Duan, Anthony Atala, Yuanyuan Zhang","doi":"10.62347/PWFE2217","DOIUrl":"10.62347/PWFE2217","url":null,"abstract":"<p><p>Renal aging contributes to declining kidney function and heightened susceptibility to chronic kidney disease (CKD). A key factor in this process is the diminished number and functionality of renal stem/progenitor cells, though the underlying mechanisms remain incompletely understood. Human urine-derived stem/progenitor cells (USCs) represent a promising, non-invasive source with notable regenerative potential. In this study, we examined cellular proliferation, reactive oxygen species (ROS) production, and senescence-associated protein expression as indicators of age-related degeneration in renal progenitor cells. USCs obtained from older healthy and diabetic individuals were compared to those from young, healthy donors. Our results demonstrate that USCs from aged and diabetic donors exhibit significantly reduced proliferation, elevated ROS levels, and increased β-galactosidase expression. Moreover, these cells showed impaired capacity to form 3D renal spheroids with tubular-like structures over a two-week culture period, relative to young controls. Together, these findings suggest that USCs from older or diabetic individuals - when cultured in both 2D and 3D systems - serve as a valuable model for studying renal aging and progenitor cell dysfunction. This model may facilitate the identification of biomarkers for renal aging and CKD risk and inform future regenerative and therapeutic strategies.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"13 5","pages":"332-341"},"PeriodicalIF":1.4,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
David S Buchinsky, Rajpal Aujla, Robert B Bracken, Salahuddin Syed, Hari Polenakovik, Albert S Malcolm, Jonathan I Hakim
{"title":"Clear cell urothelial carcinoma: a rare but villainous and hostile subtype.","authors":"David S Buchinsky, Rajpal Aujla, Robert B Bracken, Salahuddin Syed, Hari Polenakovik, Albert S Malcolm, Jonathan I Hakim","doi":"10.62347/BINQ8997","DOIUrl":"10.62347/BINQ8997","url":null,"abstract":"<p><p>Clear Cell Urothelial Carcinoma (CCUC) is a rarely reported urothelial carcinoma variant first described in 1995. Due to CCUC's clinical rarity, reporting additional cases may aid future clinicians on surgical and oncological management. We present a case of an 89-year-old male with primary CCUC and highlight the aberrant histopathological findings with a literature review. This study aims to add to current descriptions of CCUC and inform surgical and oncological management in future patients. An 89-year-old male with a history of smoking presented to clinic with painless hematuria of six months duration. Imaging showed right-sided hydroureteronephrosis down to a bladder mass. This was confirmed to be a bladder tumor on office cystourethroscopy. Following TURBT procedure, the pathology report came back suggesting 3.6 cm superficial low-grade Ta CCUC. Five months later, the patient presented with hematuria, acute kidney injury, and anemia. He was found to have T3a muscle-invasive urothelial carcinoma. This was confirmed on additional analysis which showed an FGFR3 mutation and abundant glycogen-filled clear cells. Histologically, CCUC is characterized by a glycogen-rich clear cytoplasm, severe atypia and a \"nested\" growth pattern. CCUC may be differentiated from non-CCUC by as few as a 30% clear cell change morphology of all cells. CCUC must be differentiated from Renal Cell Carcinoma and Clear Cell Adenocarcinoma. Treatment for CCUC has varied by case, with some surgeons electing to treat with radical cystectomy while others opting for local resection. Our case helps combat the paucity of literature by further characterizing and contributing to the management of CCUC.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"13 5","pages":"342-347"},"PeriodicalIF":1.4,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhi Wang, Feng Ning, Lei Tu, Yifan Yao, Jun He, Yaowang Zhao
{"title":"NCYM facilitates cell proliferation and invasion in Wilms tumor by regulating SIX1/β-catenin axis.","authors":"Zhi Wang, Feng Ning, Lei Tu, Yifan Yao, Jun He, Yaowang Zhao","doi":"10.62347/MVNT6272","DOIUrl":"10.62347/MVNT6272","url":null,"abstract":"<p><p>Recently, accumulating studies demonstrate that some long non-coding RNAs (lncRNAs) contain open read frames and have protein/peptide-coding potential. NCYM is a 109-amino acid product encoded by lncRNA MYCNOS variant 2 that is an antisense transcript of MYCN oncogene. NCYM is amplified in human neuroblastomas and associated with poor prognosis. However, its functional role in Wilms tumor (WT) remains unclear. In this study, we identified lncRNA MYCNOS as a promising prognostic factor in Wilms tumor through bioinformatics analysis. The expression of NCYM and downstream genes was determined by western blotting. Cell proliferation, migration, and invasion were measured by CCK-8, wound healing and Transwell assays, respectively. Cell apoptosis was evaluated by flow cytometry assay. The subcutaneous xenograft and lung metastasis mouse model were established by the armpit injection or tail intravenous injection of WT cells, respectively. Our results showed that NCYM was validated to be abundantly expressed in Wilms tumor cell lines and tissues. The exogenous overexpression of NCYM promoted WT cell proliferation, migration, and invasion. The silencing of SIX1 expression abolished the pro-growth effect of NCYM and downregulated β-catenin in WT. Additionally, NCYM facilitated tumor growth and formation of lung metastasis in vivo. In summary, the exogenous overexpression of NCYM could play a critical role in WT progression by mediating SIX1 and β-catenin as an oncopromoting factor.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"13 5","pages":"316-331"},"PeriodicalIF":1.4,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ming Liu, Lingfeng Li, Soroush Rais-Bahrami, Ashok K Hemal, Anthony Atala, Yuanyuan Zhang
{"title":"Artificial intelligence in prostate cancer: navigating the new frontier of precision uro-oncology.","authors":"Ming Liu, Lingfeng Li, Soroush Rais-Bahrami, Ashok K Hemal, Anthony Atala, Yuanyuan Zhang","doi":"10.62347/ZTWJ5779","DOIUrl":"10.62347/ZTWJ5779","url":null,"abstract":"<p><p>Artificial Intelligence (AI) is revolutionizing prostate cancer (PCa) care, addressing the major clinical challenges of subjectivity and overtreatment. Our traditional tools - like PSA, DRE, mpMRI, and Gleason scoring - often lack the precision needed to distinguish truly aggressive tumors from indolent disease, leading to unnecessary morbidity in up to 50% of low-risk men. This review explains how AI, specifically machine learning (ML) and deep learning (DL), is poised to solve this. We cover AI's role from initial diagnosis, where radiomics and digital pathology boost grading accuracy and reduce inter-reader variability, to treatment selection and surgical precision through predictive models and Augmented Reality (AR) guidance. We also detail its utility in predicting biochemical recurrence (BCR) and managing long-term side effects. Finally, we address the critical barriers to adoption, including the need for large, diverse datasets (to combat algorithmic bias), the \"black box\" problem (solved by Explainable AI, XAI), and navigating FDA regulation. The future of PCa care hinges on this precise, data-driven approach.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"13 5","pages":"348-359"},"PeriodicalIF":1.4,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12629898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Renal cell carcinoma with unusual morphological features: the clinical utility of next-generation sequencing in distinguishing renal cell tumors.","authors":"Jennifer Lee, Xiuping Yu, Yunshin A Yeh","doi":"10.62347/EGWC8899","DOIUrl":"10.62347/EGWC8899","url":null,"abstract":"<p><strong>Objectives: </strong>Clear cell and papillary renal cell carcinomas (RCC) are the two most common RCC subtypes, accounting for approximately 70% and 15% of kidney cancers, respectively. Clear cell RCC is commonly associated with <i>VHL</i> alterations, while papillary RCC typically exhibits chromosomal abnormalities such as +7, +17, and -Y. Furthermore, clear cell RCCs are less likely to exhibit <i>PBRM1</i> and <i>SETD2</i> alterations. This study aims to improve the accuracy of RCC diagnosis by investigating molecular alterations in RCC cases with clear cells, papillary structures, and other atypical histological features.</p><p><strong>Methods: </strong>Nine RCC cases were retrospectively selected and analyzed using histologic slides and immunohistochemical staining for CAIX, RCC, CD10, CK7, P504S, Vimentin, and EMA. Next-generation sequencing was performed on all cases to identify genetic mutations, and cytogenetic analysis was conducted on one case.</p><p><strong>Results: </strong>The cohort consisted of nine male patients aged 49 to 68 years (mean 61.4). Surgical specimens included six radical and three partial nephrectomies; seven tumors were located in the left kidney and two in the right. Tumor sizes ranged from 0.8 to 15.2 cm. Immunohistochemical analysis revealed positive staining for RCC (6/9), CAIX (3/4), CD10 (6/6), and CK7 (5/9). In six clear cell RCCs, next-generation sequencing identified <i>VHL</i> mutations in four tumors, <i>PBRM1</i> alterations in three, and <i>SETD2</i> mutations in one. Five tumors with papillary fronds, sarcomatous components, or unclassified features harboring <i>VHL</i>, <i>PBRM1</i>, and/or <i>SETD2</i> mutations were reclassified as clear cell RCC. One clear cell RCC with leiomyomatous stroma showed <i>mTOR</i> mutations. A case of clear cell papillary renal cell neoplasm showed no reportable gene mutations. The role of a <i>FANCA</i> mutation in one papillary RCC remains uncertain. Cytogenetic analysis of one case (Case #5) revealed 50, X, -Y, +3, +7, +16, +17, +20, consistent with papillary RCC.</p><p><strong>Conclusions: </strong>Next-generation sequencing is a useful method for categorizing RCCs with clear cells, papillary features, and unusual histology. Additionally, <i>VHL</i> mutations could be a promising target for personalized treatment in clear cell RCCs and their histologic variants.</p>","PeriodicalId":7438,"journal":{"name":"American journal of clinical and experimental urology","volume":"13 4","pages":"284-293"},"PeriodicalIF":1.4,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}