Related Experiment Video
Updated: Aug 13, 2026
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
Associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 with molecular subtypes, PD-L1 expression, and FGFR3 mutational
Veronika Bahlinger1,2,3, Annalena Branz1,2,3, Pamela L Strissel1,2,3,4
1Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Aims:
Treatment options for advanced urothelial carcinoma (aUC) rapidly evolved: besides immunomodulative therapeutic options and inhibitors targeting Fibroblast growth factor receptor (FGFR) alterations, two new antibody-drug conjugates (ADC), sacituzumab govitecan (SG) and enfortumab vedotin (EV), have been approved. However, little is known about the associations of specific aUC properties and the surface target expression of TROP2 and NECTIN-4. Our aim was to characterize associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 protein and gene expression with morphomolecular and clinicopathological characteristics of aUC in two large independent cohorts.
Methods And Results:
The TCGA BLCA (n = 405) and the CCC-EMN (n = 247) cohorts were retrospectively analysed. TROP2/TACSTD2 and NECTIN-4/NECTIN-4 are highly expressed at the protein and transcript level in aUC, and their expression status did not correlate with patient survival in both cohorts. NECTIN-4/NECTIN-4 expression was higher in luminal tumours and reduced in squamous aUCs. NECTIN-4 was negative in 10.6% of samples, and 18.4% of samples had low expression (H-score <15). The TROP2 negativity rate amounted to 6.5%. TACSTD2 and NECTIN-4 expression was reduced in neuroendocrine-like and/or protein-based double-negative tumours. TROP2- and NECTIN-4-negative tumours included one sarcomatoid and four neuroendocrine aUC. FGFR3 alterations and PD-L1 expression on tumour and immune cells did not associate with TROP2 or NECTIN-4 expression.
Conclusions:
TACSTD2/TROP2 and NECTIN-4/NECTIN-4 are widely expressed in aUC, independent of FGFR3 alterations or PD-L1 expression, thus representing a suitable target for ADC treatment in the majority of aUC. The expression loss was associated with aggressive morphomolecular aUC subtypes, i.e. neuroendocrine(-like) and sarcomatoid aUC.
Insights
TROP2 and NECTIN-4 are widely expressed in advanced urothelial carcinoma (aUC), making them suitable targets for antibody-drug conjugate (ADC) therapy. Expression loss in aUC correlates with aggressive subtypes, indicating potential for targeted treatment strategies.
Area of Science:
- Oncology
- Translational Research
- Molecular Pathology
Background:
- Advanced urothelial carcinoma (aUC) treatment landscape is evolving with new therapies including antibody-drug conjugates (ADCs).
- Limited understanding exists regarding the correlation between specific aUC characteristics and the expression of TROP2 and NECTIN-4, key targets for ADCs.
Purpose of the Study:
- To investigate the association between TACSTD2/TROP2 and NECTIN-4/NECTIN-4 protein and gene expression.
- To correlate target expression with morphomolecular and clinicopathological features in aUC using two independent cohorts.
Main Methods:
- Retrospective analysis of two large aUC cohorts: TCGA BLCA (n=405) and CCC-EMN (n=247).
- Assessment of TROP2/TACSTD2 and NECTIN-4/NECTIN-4 protein and transcript levels.
- Correlation analysis with clinicopathological and molecular characteristics, including FGFR3 alterations and PD-L1 expression.
Main Results:
- High expression of TROP2 and NECTIN-4 was observed at both protein and transcript levels in aUC, independent of patient survival.
- NECTIN-4 expression was higher in luminal tumors and reduced in squamous aUCs; TROP2 and NECTIN-4 expression was decreased in neuroendocrine-like and sarcomatoid subtypes.
- FGFR3 alterations and PD-L1 expression did not correlate with TROP2 or NECTIN-4 expression levels.
Conclusions:
- TROP2 and NECTIN-4 are broadly expressed in aUC, supporting their utility as targets for ADC therapy in most patients.
- Loss of TROP2/NECTIN-4 expression is linked to aggressive aUC subtypes, such as neuroendocrine(-like) and sarcomatoid variants.
More Related Videos
09:243-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
Published on: September 13, 2018
07:47Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
Published on: September 15, 2023
Related Concept Videos
02:39lncRNA - Long Non-coding RNAs
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...