MTAP protein status is highly concordant with CDKN2A fluorescent in situ hybridization and allows stratification of the luminal subtype in muscle‐invasive bladder cancer DOI Creative Commons
Ekaterina Olkhov‐Mitsel, Alexander Oberc, Kenneth J. Craddock

и другие.

Histopathology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 26, 2024

Aims Loss of heterozygosity in chromosome 9p21, common urothelial carcinoma (UC), typically involves deletion CDKN2A and MTAP genes. loss is emerging as a promising therapeutic target predictive biomarker UC. This single‐centrre retrospective study examined the incidence deletions muscle‐invasive bladder cancer (MIBC) metastatic (mUC), investigating their correlations with clinical, pathological, genomic features, well patient outcomes. Methods Fluorescence situ hybridization (FISH) immunohistochemistry (IHC) were performed on 302 MIBC specimens 63 biopsy‐proven metachronous metastases to assess protein expression. Results homozygous (HD), identified 30.3% MIBCs, loss, found 28.8% both significantly associated luminal‐URO subtype, FGFR3 mutations, normal/wildtype p53 IHC ( P < 0.05). expression was correlated HD, 84.0% sensitivity, 92.3% negative value (NPV), 96.3% specificity, 91.9% positive (PPV). 100% concordant between primary tumours nodal metastases. Patients had higher visceral (50%) compared bone/soft tissue (35.7%) nodes (14.3%). Mean progression‐free survival overall shorter for patients although not statistically significant. Conclusion Our findings highlight HD prevalent genetic alterations mUC, particularly within subtype ‐mutated, p53‐normal/wildtype tumours. can serve surrogate marker 9p21.3 highlighting its clinical relevance potential MIBC.

Язык: Английский

Spatial expression of HER2, NECTIN4, and TROP-2 in Muscle-Invasive Bladder Cancer and metastases: Implications for pathological and clinical management DOI Creative Commons

Gabriel Dernbach,

Marie‐Lisa Eich, Mihnea P. Dragomir

и другие.

Modern Pathology, Год журнала: 2025, Номер unknown, С. 100753 - 100753

Опубликована: Март 1, 2025

Muscle-invasive bladder cancer (MIBC) presents significant treatment challenges. Antibody-drug conjugates (ADCs) targeting HER2, TROP-2, and NECTIN4 offer promising therapeutic options. This study examined the spatial expression of in MIBC metastases, their association with molecular subtypes, clinical outcomes. Formalin-fixed, paraffin-embedded (FFPE) tissue samples from 251 patients were analyzed using immunohistochemistry microarrays (TMA). Expression patterns between tumor front (TF) center (TC) compared, statistical analyses assessed associations subtypes parameters. Additionally, 67 matched lymph node metastases a secondary cohort comprising 16 distant including seven primary tumors, to explore advanced stages. In HER2 was predominantly negative (83%) but showed higher positivity TC. TROP-2 exhibited high overall (58% score 3+), while displayed heterogeneity stronger Spatial overexpression at relative associated better disease free survival. Accurate assessment required four biopsies for three TROP-2. urothelial-like genomically unstable whereas widely expressed except mesenchymal-like subtype. absence staining basal, mes-like Sc/Nec-like subtypes. Paired scores all markers, reduced expression. revealed considerable compared tumors. The necessitates multiple biopsies, particularly TC, accurate evaluation. These findings underscore need personalized strategies MIBC, considering increased risk relapse Implementing multi-biopsy approach is critical enhance diagnostic accuracy.

Язык: Английский

Процитировано

0
Hot Spots in Urogenital Basic Cancer Research and Clinics DOI Open Access
Claudia Manini, Gorka Larrinaga, J.C. Angulo

и другие.

Cancers, Год журнала: 2025, Номер 17(7), С. 1173 - 1173

Опубликована: Март 31, 2025

Urogenital cancer is very common in the male population of Western countries, a problem major concern for public health systems, and frequent test subject oncological research. In this narrative, we identify main hot topics clinics basic science urological last few years (from 2021 onwards), considering information given abstracts almost 300 original articles published outstanding journals pathology, urology, science. Once defined, top ten list (the 2022 WHO update on classification urinary genital tumors, new entities kidney cancer, cancer-omics, Gleason grading system, targeted therapies other novel renal news non-muscle invasive urothelial carcinoma, artificial intelligence urologic intratumor heterogeneity influence therapeutic failures neoplasms, microbiome its tumor aggressiveness, ecological principles mathematics applied to urogenital study), each issue independently reviewed an attempt put together most relevant updates and/or useful features accompanied by selected illustrations. This review article addresses some interesting current spots research mainly aimed toward clinicians, including pathologists, urologists, oncologists. Readers are invited explore topic further, more detailed information, addition references provided.

Язык: Английский

Процитировано

0
Prognostic impact of combined loss of RB1, p53 and p21 in muscle-invasive bladder cancer DOI Creative Commons
Benedikt Ebner, Lennert Eismann,

Julian Hermans

и другие.

Pathology - Research and Practice, Год журнала: 2025, Номер unknown, С. 155960 - 155960

Опубликована: Апрель 1, 2025

Muscle-invasive bladder cancer (MIBC) represents a genetically heterogeneous disease with limited prognostic markers. This study aimed to validate the relevance of combined alterations in cell cycle regulators RB1, p53, and p21 broad cohort MIBC patients undergoing radical cystectomy (RC). We analyzed formalin-fixed paraffin-embedded material from who underwent RC at Department Urology, University Hospital, Ludwig-Maximilians-University Munich. Tissue microarrays (TMAs) 251 (pT2-pT4) were constructed, incorporating triplicate cores tumor center front. Immunohistochemical expression was assessed using four-grade scoring system. Prognostic associations overall survival (OS) cancer-specific (CSS) evaluated multivariable Cox regression, Kaplan-Meier curves, log-rank tests. 4518 stainings patients. Single marker analysis revealed no significant association between loss or OS CSS. However, two three markers significantly associated worse (HR 3.49, 95 % CI 1.28-9.50; p = 0.01) CSS 11.2, 1.46-86.04; 0.02). are insufficient as single but demonstrate when combination. These findings underscore need for multi-marker approaches modeling personalized treatment strategies MIBC.

Язык: Английский

Процитировано

0
Molecular subtypes of bladder cancer do not display microenvironment- or metastasis-induced plasticity DOI
Carina Bernardo, Subhayan Chattopadhyay, Natalie Andersson

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 10, 2025

Abstract Background Transcriptomic and genomic analyses of bladder cancer (BC) reveal a highly diverse disease stratified into molecular subtypes with distinct features biological behaviors. Intratumor heterogeneity (ITH) plasticity can significantly impact diagnosis patient management, yet their extent in BC remains debated.Methods Here, we investigated whether the three main maintain or alter identity response to changes microenvironment during metastatic colonization.Results Comprehensive longitudinal multiomics analysis PDX tumors, integrating RNA exome sequencing, SNP arrays, histopathology, demonstrated that tumors retain subtype, transcriptomic profiles across anatomical sites. No evidence emerging ITH subtype transitions was observed, regardless microenvironment. The adaptations observed metastases different primary tumor sites are limited associated primarily hypoxia, epithelial-mesenchymal transition (EMT), invasion.Conclusions Our results suggest invasive cancers have strong intrinsic is not easily reprogrammed by

Язык: Английский

Процитировано

0
Protein-Based Predictive Biomarkers to Personalize Neoadjuvant Therapy for Bladder Cancer—A Systematic Review of the Current Status DOI Open Access
Stacy R. Bedore,

Joshua van der Eerden,

Faizan Boghani

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(18), С. 9899 - 9899

Опубликована: Сен. 13, 2024

The clinical outcome of patients with muscle-invasive bladder cancer (MIBC) is poor despite the approval neoadjuvant chemotherapy or immunotherapy to improve overall survival after cystectomy. MIBC subtypes, immune, transcriptome, metabolomic signatures, and mutation burden have potential predict treatment response but none been incorporated into practice, as tumor heterogeneity lineage plasticity influence their efficacy. Using PRISMA statement, we conducted a systematic review literature, involving 135 studies published within last five years, identify reporting on prognostic value protein-based biomarkers for therapy in MIBC. were grouped based related molecular stem cell, actin-cytoskeleton, epithelial–mesenchymal transition, apoptosis, tumor-infiltrating immune cells. These show biomarkers, especially spatial context, reduce biomarker’s capability. Nevertheless, currently, there little consensus methodology, reagents, scoring systems allow reliable assessment interest. Furthermore, small sample size several necessitates validation larger multicenter cohorts before use individualizing regimens

Язык: Английский

Процитировано

3
Robust consensus molecular subtyping of muscle-invasive bladder cancer via 3' RNA sequencing of FFPE tissues: potential impact for clinical and trial settings DOI Creative Commons
Miriam Angeloni, Sven Wach,

Helge Taubert

и другие.

Laboratory Investigation, Год журнала: 2025, Номер unknown, С. 104191 - 104191

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0
Recent contributions of single-cell and spatial profiling to the understanding of bladder cancer DOI Creative Commons

Reinhard Grausenburger,

Paula Herek,

Shahrokh F. Shariat

и другие.

Current Opinion in Urology, Год журнала: 2024, Номер 34(4), С. 236 - 243

Опубликована: Апрель 22, 2024

Current risk stratification and treatment decision-making for bladder cancer informed by histopathology as well molecular diagnostics face limitations. This review summarizes recent advancements in single-cell spatial omics methodologies understanding biology their potential impact on development of novel therapeutic strategies.

Язык: Английский

Процитировано

2
Histomolekulare Klassifikation des Urothelkarzinoms der Harnblase DOI Creative Commons

Alexandra K. Stoll,

Florestan Koll, Markus Eckstein

и другие.

Deleted Journal, Год журнала: 2024, Номер 45(2), С. 106 - 114

Опубликована: Янв. 29, 2024

Of all urothelial carcinomas (UCs), 25% are muscle invasive and associated with a 5-year overall survival rate of 50%. Findings regarding the molecular classification muscle-invasive (MIUCs) have not yet found their way into clinical practice.

Язык: Английский

Процитировано

0
MTAP protein status is highly concordant with CDKN2A fluorescent in situ hybridization and allows stratification of the luminal subtype in muscle‐invasive bladder cancer DOI Creative Commons
Ekaterina Olkhov‐Mitsel, Alexander Oberc, Kenneth J. Craddock

и другие.

Histopathology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 26, 2024

Aims Loss of heterozygosity in chromosome 9p21, common urothelial carcinoma (UC), typically involves deletion CDKN2A and MTAP genes. loss is emerging as a promising therapeutic target predictive biomarker UC. This single‐centrre retrospective study examined the incidence deletions muscle‐invasive bladder cancer (MIBC) metastatic (mUC), investigating their correlations with clinical, pathological, genomic features, well patient outcomes. Methods Fluorescence situ hybridization (FISH) immunohistochemistry (IHC) were performed on 302 MIBC specimens 63 biopsy‐proven metachronous metastases to assess protein expression. Results homozygous (HD), identified 30.3% MIBCs, loss, found 28.8% both significantly associated luminal‐URO subtype, FGFR3 mutations, normal/wildtype p53 IHC ( P < 0.05). expression was correlated HD, 84.0% sensitivity, 92.3% negative value (NPV), 96.3% specificity, 91.9% positive (PPV). 100% concordant between primary tumours nodal metastases. Patients had higher visceral (50%) compared bone/soft tissue (35.7%) nodes (14.3%). Mean progression‐free survival overall shorter for patients although not statistically significant. Conclusion Our findings highlight HD prevalent genetic alterations mUC, particularly within subtype ‐mutated, p53‐normal/wildtype tumours. can serve surrogate marker 9p21.3 highlighting its clinical relevance potential MIBC.

Язык: Английский

Процитировано

0