ArticleClinical genitourinary cancer2023
Metastatic Bladder Cancer Expression and Subcellular Localization of Nectin-4 and Trop-2 in Variant Histology: A Rapid Autopsy Study.
Article in Clinical genitourinary cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Histological Subtypes and Divergent Differentiation of Urothelial Carcinoma: Histology, Genomics, and Management Implications.European urology · 2026Review
- Article
- Antibody-drug conjugate-related marker heterogeneity between primary tumors and metastatic lymph nodes in advanced urothelial cancers.Journal of translational internal medicine · 2026Article
- [Diagnosis and treatment of urothelial carcinoma of the bladder with divergent histology].Urologie (Heidelberg, Germany) · 2026Review
- Deep learning-based non-invasive profiling of tumor transcriptomes from cell-free DNA for precision oncology.bioRxiv : the preprint server for biology · 2026Article
- The emerging role of TROP2 as a diagnostic and prognostic biomarker in bladder tumor.Cancer cell international · 2026Review
- Emerging Molecular and Computational Biomarkers in Urothelial Carcinoma: Innovations in Diagnosis, Prognosis, and Therapeutic Response Prediction.Journal of personalized medicine · 2026Review
- Reduced Nectin-4 expression in lymph node metastases of penile squamous cell carcinoma: a paired primary-metastatic analysis.Frontiers in oncology · 2026Article
- Spatial distribution and subtype-specific expression patterns of Nectin-4 in muscle-invasive bladder cancer.BJU international · 2025Article
- Patterns of HER2 Expression in Metastatic Prostate and Urothelial Cancers: Implications for HER2-Targeted Therapies.Cancer research communications · 2025Article
- Evaluating the Therapeutic Role of Lymph Node Dissection in Variant Subtype Bladder Cancer.Cancers · 2025Article
- Trop-2 and Ephrin B2 expression in urothelial carcinoma with divergent differentiation and aggressive urothelial carcinoma subtypes.American journal of clinical pathology · 2025Article
- The Significance of Nectin Family Proteins in Various Cancerogenous Processes.International journal of molecular sciences · 2025Review
- Histopathologic Progression and Metastatic Relapse Outcomes in Small Cell Neuroendocrine Carcinomas of the Urinary Tract.Cancer medicine · 2025Article
- Advances in Therapy for Urothelial and Non-Urothelial Subtype Histologies of Advanced Bladder Cancer: From Etiology to Current Development.Biomedicines · 2025Review
- Article
- Durable Objective Response to Lurbinectedin in Small Cell Bladder Cancer with TP53 Mutation: A Molecular-Directed Strategy.Current oncology (Toronto, Ont.) · 2024Article
- Antibody-Drug Conjugates in the Treatment of Genitourinary Cancers: An Updated Review of Data.Current oncology (Toronto, Ont.) · 2024Review
- Prognostic Impact of Histologic Subtype and Divergent Differentiation in Patients with Metastatic Urothelial Carcinoma Treated with Enfortumab Vedotin: A Multicenter Retrospective Study.Current oncology (Toronto, Ont.) · 2024Article
- Single-cell and spatial transcriptome sequencing uncover a platinum-resistant cluster overexpressed TACSTD2 in high-grade serous ovarian cancer.Journal of Cancer · 2024Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundNectin-4 and Trop-2 are transmembrane targets of FDA-approved antibody-drug conjugates (ADC) Enfortumab-vedotin (EV) and Sacituzumab govitecan (SG), respectively, for the treatment of metastatic urothelial carcinoma (mUC). The expression and role of Nectin-4 and Trop-2 in mUC variant histology is poorly described. MATERIALS AND
methodsWe evaluate membranous and cytoplasmic protein expression, and mRNA levels of Nectin-4 and Trop-2 within matched primary and metastatic mUC samples to determine heterogeneity of ADC targets in mUC variants.
resultsPatients with mUC were consented for rapid autopsy immediately after death. Tissues from matched primary and metastatic lesions were collected. A total of 67 specimens from 20 patients were analyzed: 27 were UC, 17 plasmacytoid (PUC), 18 UC with squamous differentiation (UCSD), and 5 neuroendocrine (NE); 10 from primary and 57 from metastatic sites. All histology except NE expressed moderate-high levels of Nectin-4 and Trop-2 by both immunohistochemistry and RNAseq. Nectin-4 demonstrated prominent cytoplasmic staining in metastatic PUC and UCSD. Trop-2 demonstrated strong cytoplasmic and membrane staining in primary and metastatic tumors. Interestingly, Nectin-4 and Trop-2 expression are positively correlated at both mRNA and protein levels.
conclusionUC and non-NE variants express notable level of Nectin-4 and Trop-2 in both primary and metastatic lesions. Membrane staining of Nectin-4 and Trop-2 is present but cytoplasmic staining is a more common event in both mUC and mUC variant histology. These findings support evaluation of EV and SG in heavily treated variant histology BC and urge attention on the clinical relevance of cytoplasmic localization of ADC targets.
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