Clear cell renal cell carcinoma (ccRCC) exhibits aberrant lipid synthesis, yet how this metabolic reprogramming influences ferroptosis-a form of regulated cell death driven by lipid peroxidation-remains poorly understood. This study demonstrates that the key lipid transcription factor SREBP1 acts as a master regulator that promotes ccRCC progression by suppressing ferroptosis. Using SREBP1-knockdown cell models, we found that SREBP1 depletion enriches ferroptosis-related pathways and enhances ferroptosis sensitivity, as evidenced by elevated mitochondrial ROS, labile iron pool, PE-OOH levels, and characteristic mitochondrial alterations. Mechanistically, SREBP1 transcriptionally represses the pro-ferroptotic gene ACSL4 while simultaneously activating the lipid-synthesis gene FASN. Rescue experiments revealed that modulating either ACSL4 or FASN alone only partially reverses the ferroptosis phenotype induced by SREBP1 loss, whereas dual manipulation of both genes fully restores ferroptosis resistance. Metabolomic analyses showed that ACSL4 and FASN converge to regulate the cellular PUFAs/MUFAs ratio, which in turn feeds back to modulate SREBP1 nuclear translocation, thereby establishing a self-reinforcing positive-feedback loop. Clinically, low ACSL4 expression correlates with advanced tumor stage and poor patient survival. In vivo, SREBP1 promotes tumor growth by inhibiting ferroptosis via the ACSL4/FASN axis. Collectively, our findings reveal that SREBP1 drives ccRCC malignancy through a dual-pronged mechanism-repressing ACSL4 and activating FASN-to alter the PUFAs/MUFAs balance and establish a feed-forward loop that sustains ferroptosis suppression. ACSL4 represents a potential prognostic biomarker, and targeting the SREBP1-ACSL4/FASN axis offers a promising therapeutic strategy for ccRCC.

Backgrounds: Bladder cancer shows pronounced biological heterogeneity that underlies its variable clinical course and prognosis. Our study aims to delineate clinically relevant differences in bladder cancer using an immunohistochemistry-based molecular subtyping approach. Methods: This retrospective study included 590 patients with bladder cancer treated at a single center. Tumors were stratified into luminal versus non-luminal categories according to CK20, GATA3, CK5/6, and CK14. Associations between molecular subtype, histopathological growth patterns, pathological response to neoadjuvant chemotherapy (NAC), and clinical survival endpoints were analyzed. Overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS) were evaluated through Kaplan-Meier survival curves together with Cox proportional hazards regression analyses. Results: Non-luminal tumors exhibited significantly more aggressive pathological growth patterns, including higher levels of tumor budding (p = 0.002), a predominance of non-cohesive or spindle/single-cell architecture (p = 0.003), and more frequent disseminated spreading patterns (p = 0.001), whereas luminal tumors more commonly displayed a higher frequency of tertiary lymphoid structures (TLSs; p = 0.041). Among patients receiving NAC, non-luminal tumors achieved a significantly higher pathological complete response (pCR) rate compared with luminal tumors (p = 0.007), while no significant inter-subtype difference was detected in pathological downstaging between subtypes (p = 0.126). Despite inferior pathological response, luminal tumors demonstrated significantly improved OS (p = 0.003), RFS (p = 0.002) and PFS (p < 0.001) compared with non-luminal tumors. In multivariable Cox regression analysis, molecular subtype was identified as an independent predictor of OS, with luminal tumors showing a lower mortality risk (HR = 0.51, 95% CI 0.33-0.79, p = 0.003). Conclusions: These findings indicate that pathological response and long-term survival follow distinct, subtype-dependent trajectories in bladder cancer. Favorable pathological response does not necessarily correspond to improved long-term survival across molecular subtypes.

To develop and validate a non-invasive imaging-based intratumor heterogeneity (IITH) framework for risk stratification in muscle-invasive bladder cancer (MIBC) and to investigate its association with survival outcomes and molecular subtypes. In this retrospective multicenter study, 437 MIBC patients were enrolled (237 patients of discovery cohort and 102 patients of validation cohort predominantly underwent radical cystectomy (RC); 98 patients of NAC cohort received three to four cycles of gemcitabine-cisplatin chemotherapy prior to surgery). From pretreatment MRI scans, 42 radiomic features were extracted. Unsupervised consensus clustering was performed using the “ConsensusClusterPlus” R package, a resampling-based method which generates a consensus matrix to robustly stratify cohorts into stable IITH subtypes. Prognostic significance for OS, CSS, RFS, PFS was then evaluated based on data reviewed up to July 30, 2024. Molecular correlates were assessed via immunohistochemistry and transcriptomic data from The Cancer Genome Atlas. The IITH framework significantly stratified patient survival in the discovery cohort (OS: HR = 1.646, p < 0.05; CSS: HR = 1.792, p < 0.05; RFS: HR = 2.06, p < 0.01; PFS: HR = 1.721, p = 0.01), with consistent results in external validation cohorts (OS: HR = 2.604, p < 0.05; RFS: HR = 2.422, p < 0.05; PFS: HR = 2.72, p < 0.05). High-IITH tumors demonstrated greater histological diversity and enriched mixed subtypes. In the NAC cohort, high IITH was associated with markedly worse outcomes (CSS: HR = 7.795, p < 0.05; RFS: HR = 9.529, p < 0.001; PFS: HR = 8.893, p < 0.001). Transcriptomic analysis revealed elevated inflammatory activity and enhanced proliferative/migratory potential in high-IITH groups. The MRI-based IITH framework effectively stratified MIBC patients by prognosis and treatment response, with high heterogeneity being associated with adverse outcomes and aggressive molecular tumor biology.

BACKGROUND/OBJECTIVES:The available risk stratification models used to predict the prognosis of non-muscle-invasive bladder cancer (NMIBC) are not efficient enough. The research focused on assessing the relationship between HER2 expression status and recurrence in NMIBC. METHODS:The retrospective study consisted of 217 NMIBC patients who were treated by transurethral resection of bladder tumor. Immunohistochemistry (IHC) was used to evaluate HER2 expression as being high (IHC 2+/3+) or low (IHC 0/1+). The relationship between the clinicopathological characteristics and the recurrence-free survival (RFS) was examined through the use of both univariate and multivariate Cox proportional hazards regression. The additional predictive utility of HER2 to the European Organization for Research and Treatment of Cancer (EORTC) and Club Urológico Español de Tratamiento Oncológico (CUETO) models was determined based on the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (t-AUC). RESULTS:The patients who had high HER2 expression (n = 96) had significantly increased rates of pT1 stage (39.6% vs. 18.2%, P < .001), high-grade tumor (75.0% vs. 44.6%, P < .001), and recurrent tumor (29.2% vs. 13.2%, P = .004) when compared to the low-expression group. Multivariate analysis identified high HER2 expression as an independent predictor of recurrence (HR 2.58, 95% CI, 1.41-4.73; P = .002). HER2-high patients had significantly worse RFS. Subgroup analyses showed worse RFS for HER2-overexpressing tumors across intravesical instillation subgroups and within the European Association of Urology (EAU) intermediate- and high-risk groups (all P < .05). Integrating HER2 status significantly improved the predictive performance of both the EORTC (C-index: 0.703-0.730) and CUETO models (C-index: 0.687-0.716). CONCLUSION:High HER2 expression is an independent risk predictor of recurrence in NMIBC patients. It provides significant incremental prognostic value beyond EORTC and CUETO risk scores and enhances risk stratification within intermediate- and high-risk EAU groups.

目的探讨松果体实质肿瘤的临床病理特征、分子遗传学特点及鉴别诊断。方法收集南京医科大学第一附属医院2016—2024年间4例松果体实质肿瘤, 分析其影像学、病理学及分子遗传学特征, 并复习文献。结果患者男女各2例, 发病年龄32～64岁, 中位年龄52岁。1例松果体细胞瘤, WHO 1级, 镜下可见特征性的松果体细胞瘤性菊形团, 核分裂象罕见。3例中分化松果体实质肿瘤(PPTID), 1例WHO 2级, 2例WHO 3级, 镜下观察肿瘤呈弥漫片状和分叶状排列。高级别肿瘤细胞核呈胡椒盐样, 核分裂象6个/10 HPF。免疫表型:肿瘤组织突触素、嗜铬粒素A、神经元特异性烯醇化酶均为阳性, 神经丝蛋白在松果体细胞瘤中弥漫表达, 而在PPTID中表达减弱。分子遗传学:2例PPTID分别检测出HRAS扩增和KBTBD4第4号外显子的非移码插入突变。结论松果体实质肿瘤是一组罕见的异质性较强的肿瘤, 诊断需依赖组织学形态、免疫组织化学及分子遗传学检测;松果体细胞瘤预后良好, PPTID具有局部复发进展和软脑膜播散的潜能, 术后需联合治疗。本研究检测到PPTID中新的KBTBD4突变位点及HRAS基因扩增, 拓宽了该类肿瘤的分子遗传学谱系。

Objective: Seminal vesiculitis is a prevalent infectious disease in the genitourinary system, but its intrinsic pathogenesis and molecular features remain unclear. Methods: In this study, we utilized a next-generation sequencing technology to demonstrate transcriptomic landscapes of clinical specimens from seminal vesiculitis patients. We identified enriched Go Ontology terms, pathway maps, processes, toxicity, and metabolic networks of seminal vesiculitis. Results: Glutathione S-transferase activity is highly enriched, indicating its essential role in the disease's development. Furthermore, we established inflammation models of the seminal vesicle and verified the crucial function of glutathione S-transferase activity in these models. Conclusion: Glutathione S-transferase serves an essential role in seminal vesiculitis patients. Our results shall provide a robust platform for further intensive studies of seminal vesiculitis.

Background Accurate prognosis prediction in bladder cancer (BCa) is crucial for personalized treatment. This study aimed to develop and validate a non-invasive model using magnetic resonance imaging (MRI) for predicting the overall survival (OS) in patients with BCa. Methods This retrospective multicentre study included 1131 patients with BCa from eight institutions in China from June 2011 to March 2024. 871 patients were enrolled from one centre, who were randomly divided (8:2) into training (n = 697) and internal validation (n = 174) sets. For the external test set, 260 patients with BCa from seven centres were retrospectively included. We developed a multimodal fusion deep learning model (MF-DLM), leveraging a cross-attention mechanism to integrate four key preoperative data modalities: three-dimensional (3D) deep learning features using a modified 3D ResNet50 network, 3D radiomics features, morphological MRI features, and clinical features. Patients were stratified into low- and high-risk prognostic groups based on MF-DLM scores, and model interpretability was evaluated using Shapley additive explanations (SHAP) and Gradient-weighted class activation mapping (Grad-CAM). Findings The median follow-up time for the training, validation, and external test sets are 38.0 months (interquartile ranges [IQR]: 22.0, 62.0), 40.5 months (IQR: 23.0, 71.0), and 38.5 months (IQR: 26.0, 50.0), respectively. The MF-DLM demonstrated excellent performance in predicting OS, achieving higher C-index values than pathological T stage (training: 0.902 vs. 0.793, p < 0.001; validation: 0.864 vs. 0.757, p = 0.014; external test: 0.841 vs. 0.760, p = 0.047). In addition, MF-DLM-based low-risk group demonstrated significantly longer OS in the training, validation, and external test sets (p < 0.001). In the adjuvant therapy (AT) cohort, high-risk patients had significantly worse prognosis compared with low-risk patients (p < 0.0001). Additionally, high-risk pathological T3/4 patients exhibited no statistically significant OS difference between those who received AT and those who did not (p = 0.18), whereas low-risk pathological T3/4 patients experienced significantly improved OS with AT (p = 0.0059). Besides, the low-risk group had better OS than the high-risk group in neoadjuvant therapy cohort (p = 0.0032). Interpretation The MF-DLM can reliably predict OS in patients with BCa and provide additional prognostic stratification beyond pathological T and N stages. Furthermore, MF-DLM-based risk groups can identify patients most likely to benefit from perioperative therapy. Funding The Noncommunicated Chronic Diseases-National Science and Technology Major Project (2024ZD0525700); National Natural Science Foundation of China (82273152, 82503879), Jiangsu Province Hospital (the First Affiliated Hospital of Nanjing Medical University) Clinical Capacity Enhancement Project (JSPH-MA-2022-5), China Postdoctoral Science Foundation funded project (2024M761211), and the Nanjing Postdoctoral Science Foundation funded project (2024BHS210).

Prostate cancer is a leading health concern for men, yet current clinical assessments of tumor aggressiveness rely on invasive procedures that often lead to inconsistencies. There remains a critical need for accurate, noninvasive diagnosis and grading methods. Here we developed a foundation model trained on multiparametric magnetic resonance imaging (MRI) and paired pathology data for noninvasive diagnosis and grading of prostate cancer. Our model, MRI-based Predicted Transformer for Prostate Cancer (MRI-PTPCa), was trained under contrastive learning on nearly 1.3 million image-pathology pairs from over 5,500 patients in discovery, modeling, external and prospective cohorts. During real-world testing, prediction of MRI-PTPCa demonstrated consistency with pathology and superior performance (area under the curve above 0.978; grading accuracy 89.1%) compared with clinical measures and other prediction models. This work introduces a scalable, noninvasive approach to prostate cancer diagnosis and grading, offering a robust tool to support clinical decision-making while reducing reliance on biopsies.

Primary aldosteronism (PA) caused by aldosterone hypersecretion is treated by adrenalectomy or medications. Histopathologic examination of resected adrenals reveals diverse histopathologic features. This study aimed to investigate the potential association of peripheral and adrenal tissue metabolic profiles with the histopathologic features of PA. The retrospective study included 105 surgically treated and 43 medically treated patients with PA. Adrenal specimens were categorized according to the HISTALDO (HISTopathology of primary ALDOsteronism) consensus. Peripheral and adrenal tissue metabolic profiles were assessed, including adiposity, adipokines and fatty acid abundances. The distinct fatty acid, arachidonic acid, was further functionally characterized. Surgically treated patients with classical histopathologic findings (n = 71) displayed lower body mass indexes, a lower prevalence of obesity, smaller waist circumference and visceral adipose tissue areas, and lower leptin concentrations compared with operated patients with the nonclassical histopathology (n = 34). No such differences were identified between the nonclassical histopathology group and medically treated group. Distinct concentrations of 18 out of 35 peripheral venous fatty acids, including arachidonic acid, were identified among the 3 groups. Further, accumulation of arachidonic acid was demonstrated in 4 aldosterone-producing adenomas compared with paired adjacent cortex possibly linked with suppressed peroxisomal beta-oxidation. Stimulation of human adrenocortical cells with arachidonic acid or peroxisomal beta-oxidation inhibitor caused 3.8-fold (P = 0.0050) and 1.7-fold (P = 0.0328) amplification of CYP11B2 expression, respectively, which were ablated by BAPTA-AM or KN93, and induced oxidative stress and apoptosis. Our findings show metabolic heterogeneity related to histopathology and support a role for arachidonic acid in PA pathophysiology.

The cyclin-dependent kinase inhibitor 3 (CDKN3) gene, is over expressed in renal cell carcinoma (RCC). However, the cell biology functions of RCC are not well understood. The present study aimed to verify the ability of CDKN3 to promote the proliferation and migration of RCC through in vitro experiments. Subsequently, the clinical prognostic effects were analyzed using The Cancer Genome Atlas (TCGA; https://www.cancer.gov/) and Gene Expression Omnibus (GEO; https://www.ncbi.nlm.nih.gov/geo/). The chelators, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), an analogue of the anti-tumor agent, were screened through bioinformatics analysis. The expression of CDKN3 is positively correlated with the IC50 of Dp44mT. In two RCC cell lines, 786-0 and Caki-1,we conducted small interfering RNA (siRNA) knockdown of CDKN3 and overexpression of CDKN3 by transfection plasmid. Subsequently, we administered Dp44mT to examine the resulting alterations in cell proliferation, migration, and apoptosis, thereby elucidating the role of CDKN3 and Dp44mT in these processes. The results of the experiment revealed a positive association between CDKN3 expression and the proliferation of RCC cell lines. Down-regulating CDKN3 significantly increased the apoptosis rate and inhibited cell migration in 786-0 and Caki-1 cells. Furthermore, bioinformatics analysis revealed a high expression of CDKN3 in RCC and a negative association between CDKN3 expression and survival. Gene set enrichment analysis (GSEA) revealed a significant association between high CDKN3 expression and the cell cycle pathway. Furthermore, we identified Dp44mT as a drug highly correlated with CDKN3 through the database. Subsequent addition of Dp44mT resulted in similar findings to those observed upon CDKN3 knockdown. Our findings have important implications for the diagnosis and treatment of CDKN3 in RCC. Additionally, Dp44mT is likely to be a promising candidate for future clinical applications.

You have accessJournal of UrologyImaging/Uroradiology I (MP18)1 May 2024MP18-13 TRANSFORMER-BASED LARGE MODEL WITH MP-MRI FOR NON-INVASIVE AUXILIARY DIAGNOSIS OF PROSTATE CANCER: A MULTI-CENTER STUDY Chao Liang, Meiling Bao, Ye Yan, Zhuhong Shao, and Jie Li Chao LiangChao Liang , Meiling BaoMeiling Bao , Ye YanYe Yan , Zhuhong ShaoZhuhong Shao , and Jie LiJie Li View All Author Informationhttps://doi.org/10.1097/01.JU.0001008672.83391.ed.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The non-invasive diagnosis of prostate cancer before surgery still faces challenges and a growing need for precision diagnosis and treatment. Discordance between clinical tools (e.g. PSA, PI-RADS) and pathology leads to over-diagnosis or under-diagnosis. Transformer-based large model provides a more efficient way to build cross-scale information mapping. The study first utilizes a transformer model to analyze the correlation between mp-MRI and pathological characterization. The study aimed to provide non-invasive auxiliary diagnostic models for clinics and validate in multi-center. METHODS: Our study retrospectively collected 3008 patients who underwent pathological evaluation of the prostate from January 2013 to October 2022, which 1788 patients were from Peking University Third Hospital and 1210 patients were from The First Affiliated Hospital of Nanjing Medical University. The study proposed an MRI-based Predicted Transformer for Prostate cancer (MRI-PTPCa) to translate mp-MRI to prostate tumor aggressiveness, and use the MRI-PTPCa to predict grade group for prostate cancer. The MRI-PTPCa was trained by more than 160,000 iterations and variant training samples greater than 100,000, which were augmented from 1748 patients' mp-MRI of the training cohort. Finally, the performance of MRI-PTPCa was evaluated on more than 1,000 multi-center patients. RESULTS: The MRI-PTPCa for diagnostic tasks in prostate cancer earned performance with both accuracy and robustness. The performance of MRI-PTPCa for non-invasive diagnosis of prostate cancer yield area under the curve (AUC) of 0.981 [0.976-0.986], sensitivity (SEN) of 0.989 [0.986-0.993] and specificity (SPE) of 0.97 [0.96-0.98] in external testing. The re-diagnosis benefits of the MRI-PTPCa in the PSA gray zone have been improved, which also yielded better net benefit than clinical radiology evaluation by PI-RADS. For diagnosing clinically significant prostate cancer, MRI-PTPCa once again achieved better accuracy than the clinical method. The MRI-PTPCa yielded an overall AUC of 0.978 [0.975-0.981] for clinically significant prostate cancer diagnosis, which earned SEN of 0.998 [0.996-0.999] and SPE of 0.885 [0.867-0.902]. CONCLUSIONS: MRI-PTPCa takes advantage of mp-MRI and retrospective big data. Correlation learning between imaging and pathology helps to obtain stronger models. It demonstrates better and more robust performance in the diagnosis of prostate cancer and clinically significant prostate cancer diagnosis. Source of Funding: National Natural Science Foundation of China (grant number 82002718) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e306 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Chao Liang More articles by this author Meiling Bao More articles by this author Ye Yan More articles by this author Zhuhong Shao More articles by this author Jie Li More articles by this author Expand All Advertisement PDF downloadLoading ...

目的:探讨肾周及肾窦黏液性假瘤的临床病理学特征、诊断及鉴别诊断。方法:收集南京医科大学第一附属医院诊断的分别发生在肾周及肾窦的黏液性假瘤2例患者的临床病理资料，光镜下观察HE切片及免疫组织化学染色结果，应用荧光原位杂交（FISH）法检查MDM2基因扩增情况，并复习相关文献进行分析。结果:男女各1例，年龄分别为49岁和69岁，病变部位分别位于肾周及肾窦内。镜下观察：肿瘤由成熟脂肪、黏液样基质、梭形或星芒状纤维母细胞及间质炎性细胞混合组成，间质炎性细胞主要为淋巴细胞和浆细胞，可见淋巴滤泡形成。肿瘤细胞形态温和，染色质细腻，缺乏核分裂象及坏死。免疫组织化学：肿瘤细胞表达平滑肌肌动蛋白和CD34，不表达S-100蛋白、SOX10、STAT6、广谱细胞角蛋白（CKpan）、上皮细胞膜抗原、PAX8、MUC4、结蛋白及间变性淋巴瘤激酶（ALKp80），Ki-67阳性指数约为5%。FISH法检测显示肿瘤细胞MDM2基因无扩增。2例患者术后随访均未复发。结论:肾周及肾窦黏液性假瘤是一种少见病变，可伴有肾脏基础性疾病，认识到此病变的意义在于避免误诊，特别容易误诊为脂肪肉瘤。

Background Vesical Imaging‐Reporting and Data System (VI‐RADS) is a pathway for the standardized imaging and reporting of bladder cancer staging using multiparametric (mp) MRI. Purpose To investigate additional role of morphological (MOR) measurements to VI‐RADS for the detection of muscle‐invasive bladder cancer (MIBC) with mpMRI. Study Type Retrospective. Population A total of 198 patients (72 MIBC and 126 NMIBC) underwent bladder mpMRI was included. Field Strength/Sequence 3.0 T/T2‐weighted imaging with fast‐spin‐echo sequence, spin‐echo‐planar diffusion‐weighted imaging and dynamic contrast‐enhanced imaging with fast 3D gradient‐echo sequence. Assessment VI‐RADS score and MOR measurement including tumor location, number, stalk, cauliflower‐like surface, type of tumor growth, tumor‐muscle contact margin (TCM), tumor‐longitudinal length (TLL), and tumor cellularity index (TCI) were analyzed by three uroradiologists (3‐year, 8‐year, and 15‐year experience of bladder MRI, respectively) who were blinded to histopathology. Statistical Tests Significant MOR measurements associated with MIBC were tested by univariable and multivariable logistic regression (LR) analysis with odds ratio (OR). Area under receiver operating characteristic curve (AUC) with DeLong's test and decision curve analysis (DCA) were used to compared the performance of unadjusted vs. adjusted VI‐RADS. A P ‐value <0.05 was considered statistically significant. Results TCM (OR 9.98; 95% confidence interval [CI] 4.77–20.8), TCI (OR 5.72; 95% CI 2.37–13.8), and TLL (OR 3.35; 95% CI 1.40–8.03) were independently associated with MIBC at multivariable LR analysis. VI‐RADS adjusted by three MORs achieved significantly higher AUC (reader 1 0.908 vs. 0.798; reader 2 0.906 vs. 0.855; reader 3 0.907 vs. 0.831) and better clinical benefits than unadjusted VI‐RADS at DCA. Specially in VI‐RADS‐defined equivocal lesions, MOR‐based adjustment resulted in 55.5% (25/45), 70.4% (38/54), and 46.4% (26/56) improvement in accuracy for discriminating MIBC in three readers, respectively. Data Conclusion MOR measurements improved the performance of VI‐RADS in detecting MIBC with mpMRI, especially for equivocal lesions. Level of Evidence 3 Technical Efficacy Stage 2

BACKGROUND: To investigate the predictive ability of high-throughput MRI with deep survival networks for biochemical recurrence (BCR) of prostate cancer (PCa) after prostatectomy.METHODS: Clinical-MRI and histopathologic data of 579 (train/test, 463/116) PCa patients were retrospectively collected. The deep survival network (iBCR-Net) is based on stepwise processing operations, which first built an MRI radiomics signature (RadS) for BCR, and predicted the T3 stage and lymph node metastasis (LN+) of tumour using two predefined AI models. Subsequently, clinical, imaging and histopathological variables were integrated into iBCR-Net for BCR prediction.RESULTS: RadS, derived from 2554 MRI features, was identified as an independent predictor of BCR. Two predefined AI models achieved an accuracy of 82.6% and 78.4% in staging T3 and LN+. The iBCR-Net, when expressed as a presurgical model by integrating RadS, AI-diagnosed T3 stage and PSA, can match a state-of-the-art histopathological model (C-index, 0.81 to 0.83 vs 0.79 to 0.81, p > 0.05); and has maximally 5.16-fold, 12.8-fold, and 2.09-fold (p < 0.05) benefit to conventional D'Amico score, the Cancer of the Prostate Risk Assessment (CAPRA) score and the CAPRA Postsurgical score.CONCLUSIONS: AI-aided iBCR-Net using high-throughput MRI can predict PCa BCR accurately and thus may provide an alternative to the conventional method for PCa risk stratification.

Recent studies revealed the relationship among homologous recombination repair (HRR), androgen receptor (AR), and poly(adenosine diphosphate-ribose) polymerase (PARP); however, the synergy between anti-androgen enzalutamide (ENZ) and PARP inhibitor olaparib (OLA) remains unclear. Here, we showed that the synergistic effect of ENZ and OLA significantly reduced proliferation and induced apoptosis in AR-positive prostate cancer cell lines. Next-generation sequencing followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed the significant effects of ENZ plus OLA on nonhomologous end joining (NHEJ) and apoptosis pathways. ENZ combined with OLA synergistically inhibited the NHEJ pathway by repressing DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and X-ray repair cross complementing 4 (XRCC4). Moreover, our data showed that ENZ could enhance the response of prostate cancer cells to the combination therapy by reversing the anti-apoptotic effect of OLA through the downregulation of anti-apoptotic gene insulin-like growth factor 1 receptor (IGF1R) and the upregulation of pro-apoptotic gene death-associated protein kinase 1 (DAPK1). Collectively, our results suggested that ENZ combined with OLA can promote prostate cancer cell apoptosis by multiple pathways other than inducing HRR defects, providing evidence for the combined use of ENZ and OLA in prostate cancer regardless of HRR gene mutation status.

Angiomyolipoma (AML) complicated with tumour thrombus extending to the confluence of inferior vena cava (IVC) with right atrium is rarely observed. We report a female AML patient admitted to our centre on January 21, 2020, with complication of tumour thrombus extending to the confluence of IVC with right atrium and had no sign of difficult breathing. She underwent whole-abdominal enhanced CT for abdominal pain and was diagnosed with a possible renal AML with tumour thrombus. Open radical nephrectomy and thrombectomy of vena cava were performed. Intraoperative transoesophageal echocardiography indicated that the tumour thrombus has reached the confluence of IVC with right atrium. The operation took 255 min with an intraoperative haemorrhage of 800mL. The patient was discharged 7 days after surgery. Pathology revealed lipoma-like AML. Immunohistochemistry showed vimentin (+), EMA (-), HMB45 (+), S-100 (-), SMA (+), TFE-3 (-), melan A (+). After 2 years of follow-up, we found that the patient showed full recovery and had no recurrence. Therefore, lipoma-like AML should also be followed closely for recurrence and metastasis. When AML involves IVC tumour thrombus, open thrombectomy and radical nephrectomy are safe and effective methods.

Neuroendocrine prostate cancer (NEPC), the most lethal subtype of castration-resistant prostate cancer (PCa), may evolve from the neuroendocrine differentiation (NED) of PCa cells. However, the molecular mechanism that triggers NED is unknown. Trigred motif 36 (TRIM36), a member of the TRIM protein family, exhibits oncogenic or anti-oncogenic roles in various cancers. We have previously reported that TRIM36 is highly expressed to inhibit the invasion and proliferation of PCa. In the present study, we first found that TRIM36 was lowly expressed in NEPC and its overexpression suppressed the NED of PCa. Next, based on proteomic analysis, we found that TRIM36 inhibited the glycolysis pathway through suppressing hexokinase 2 (HK2), a crucial glycolytic enzyme catalyzing the conversion of glucose to glucose-6-phosphate. TRIM36 specifically bound to HK2 through lysine 48 (lys48)-mediated ubiquitination of HK2. Moreover, TRIM36-mediated ubiquitination degradation of HK2 downregulated the level of glutathione peroxidase 4 (GPx4), a process that contributed to ferroptosis. In conclusion, TRIM36 can inhibit glycolysis via lys48-mediated HK2 ubiquitination to reduce GPX4 expression and activate ferroptosis, thereby inhibiting the NED in PCa. Targeting TRIM36 might be a promising approach to retard NED and treat NEPC.

OBJECTIVE:To investigate the clinical feature, pathological morphology, special histopathological subtype and immunohistochemical characteristic of gonadoblastoma.METHODS:Three patients of gonadoblastoma treated from 2014 to 2020 were enrolled, and the clinical characteristics, histological morphology and immunophenotype were analyzed, and the literatures were also reviewed.RESULT:Three phenotypical females were 14,17 and 27 years old. Case 1 was 46,XX with normal gonadal development. Case 2 was 46,XY and case 3 was chromosomal chimeric type (46, XY 90%/45,X 10%), both with dysgenetic gonads. Microscopically, the morphology of classic type was observed in all cases more or less, manifesting small nests of primitive germ cells and surrounding clustered sex cord-like cells, usually with Call-Exner like bodies and calcification. In additon, the morphology of special subtype can be seen in case 1,exhibiting cord-like tumor cells, which was segmentated by cellular fibrous stroma. Cases 2 and 3 were accompanied by dysgerminoma components. Immunohistochemically,all the primal germ cells were positive for OCT3/4, PLAP and CDll7 , and sexcord-like cells were positive for inhibin, SF-1, SOX9 and FOXL2 . Patients were followed up for 10 years, 6 years and 4 years respectively without recurrence.CONCLUSION:Gonadoblastoma is a rare germ cell-sex cord stromal tumor, which is usually accompanied by gonadal hypoplasia. As a special subtype, dissecting gonadoblastoma will be easily confused with dysgerminoma/seminoma, but the prognosis is better. So we should improve the understanding of this subtype and avoid overdiagnosis.

目的 探讨透明细胞型软骨肉瘤(clear cell chondrosarcoma,CCC)的临床病理特征、诊断和鉴别诊断.方法 回顾性分析6例CCC的临床病理学特征、影像学表现、免疫表型及分子遗传学特征,行HE、免疫组化染色及基因检测,并复习相关文献.结果 6例中男性4例,女性2例,年龄26～51岁,平均年龄37.8岁;发病部位:股骨4例,肱骨1例,胸椎1例.临床表现均为长期疼痛,2例合并骨折.眼观:手术切除标本肿瘤最大径2.0～8.5 cm;镜检:肿瘤细胞呈分叶状、片状、巢团状分布,瘤细胞胞质透明,小叶中央可见骨小梁或成骨,小叶周围可见散在破骨样巨细胞,2例可见局灶经典型软骨肉瘤成分.免疫表型:肿瘤细胞S-100阳性,1例CKpan阳性,SATB2在骨母细胞中阳性,而在瘤细胞中阴性,Ki-67增殖指数为2％～5％.分子检测示IDH1/IDH2、H3F3A均为野生型.2例于术后14、44个月复发,其中1例同时转移到锁骨.结论 CCC属软骨肉瘤亚型,绝大多数位于长骨骨骺和干骺端,以股骨近端最为多见,组织病理学以透明细胞、不规则骨小梁及破骨样多核巨细胞为特征,因其临床多呈低侵袭性,正确识别该亚型可避免临床过度治疗.

Objective: To investigate the clinicopathological characteristics, pathological diagnosis of Ewing's sarcoma of the central nervous system. Methods: Six cases of Ewing's sarcoma of the central nervous system diagnosed at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from 2015 to 2022 were collected. The clinical manifestations, histological morphology, immunophenotype and molecular genetics of these cases were analyzed. The related literature was reviewed. Results: There were four males and two females, with a male to female ratio of 2∶1. The onset age was 17-40 years, with a median age of 23 years. All 6 tumors were located in the spinal cord (2 cases of cervical vertebra, 1 case of thoracic vertebra, 2 cases of lumbar vertebra, and 1 case of sacral vertebra). The patients' clinical manifestations were mostly lumbago, weakness and numbness of lower limbs/limbs. In 1 case, the tumor recurred and metastasized to the suprasellar region and the third ventricle. Microscopically, the tumor showed diffuse infiltrative growth. In some cases, the tumor was closely related to the spinal meninges. The tumor cells were arranged in sheet, lobular, thin-rope, and nest-like patterns. Homer-Wright rosette was visible. The tumor cells were small to medium in size, and most of them had scant cytoplasm. A few cells had clear cytoplasm. Some areas were rhabdoid. The tumor cell nuclei showed focal mild pleomorphism. The chromatin was uniform and delicate while the nucleoli were not obvious. Mitosis was commonly seen. The tumor was separated by fibrous connective tissue and may be accompanied by mucinous degeneration. Immunohistochemistry showed that all tumors were positive for CD99, NKX2.2, Fli1, ERG. ATRX, H3K27me3, INI1 and BRG1 were all retained. Immunohistochemical stains for EMA, GFAP and Olig2 were negative. The Ki-67 proliferation index was 30%-70%. EWSR1 break-apart FISH test was positive. Conclusions: Ewing's sarcoma is rare in the central nervous system and needs to be distinguished from a variety of neoplasms with primitive undifferentiated small cell morphology. Immunohistochemistry and molecular genetics may be required for a proper diagnosis.