ArticlePathologica2024
TROP-2, NECTIN-4 and predictive biomarkers in sarcomatoid and rhabdoid bladder urothelial carcinoma.
Article in Pathologica, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 11 citations in OpenAlex.
- Conversion to Pathological Complete Response by Enfortumab Vedotin in Metastatic Sarcomatoid Urothelial Carcinoma With Nectin-4 Expression: A Case Report.IJU case reports · 2026Article
- [Diagnostic and predictive molecular pathology of urothelial carcinoma : Current status and outlook for the future].Pathologie (Heidelberg, Germany) · 2026Review
- The emerging role of TROP2 as a diagnostic and prognostic biomarker in bladder tumor.Cancer cell international · 2026Review
- Targeted therapies for urothelial carcinoma: From FGFR inhibitors to next‑generation antibody-drug conjugates (Review).International journal of oncology · 2026Review
- High Trop-2 expression in pulmonary sarcomatoid carcinoma reveals antibody-drug conjugate targeting Trop-2 is a promising therapeutic approach.Journal of translational medicine · 2025Article
- Nectin-4-Targeting Radiotracers: Novel Theranostic Agents for Precision Oncology in Cancer.Molecular diagnosis & therapy · 2025Review
- Assessing the expression of Nectin-4 in solid tumors by immunohistochemistry - what do we know?Histology and histopathology · 2025Review
- Integrating analysis of multi-omics summary data identifies novel plasma protein biomarkers and drug targets for bladder cancer.Discover oncology · 2025Article
- Teratoma combined with struma ovarii and sarcomatoid carcinoma: a case report and review of the literature.BMC women's health · 2024Review
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21 authors at 13 institutions in 2 countries.
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Abstract
Introduction: The surface protein TROP-2/TACSTD2 and the cell adhesion protein NECTIN-4/NECTIN4 are responsible for the efficacy of anticancer therapies based on antibody-drug conjugates (ADC) targeting intracellular microtubules. In contrast with common histologic subtypes of bladder urothelial carcinoma (BUC), little is known of TROP-2 and NECTIN-4 expression in sarcomatoid and rhabdoid BUC. Aims: In this study, we aimed to analyze TROP-2 and NECTIN-4 expression and additional predictive biomarkers by immunohistochemistry and fluorescence in situ hybridization (FISH) on 35 undifferentiated BUC (28 sarcomatoid and 7 rhabdoid). Wide genomic investigation was also performed on 411 BUC cases of the PanCancer Atlas, focusing on genes related to the microtubule pathways. Results: Seven of 35 (20%) undifferentiated BUC showed expression of TROP-2. NECTIN-4 was expressed in 10 cases (29%). Seven cases (20%) co-expressed TROP-2 and NECTIN-4. HER-2 FISH was amplified in 5 cases (14%) while HER-2 immunoexpression was observed in 14 cases (40%). PD-L1 scored positive for combined proportion score (CPS) in 66% of cases and for tumor proportion score (TPS) in 51% of cases. Pan-NTRK1-2/3 was elevated in 9 cases (26%) and FGFR-2/3 was broken in 7 of 35 cases (20%). Of 28 sarcomatoid BUC, 9 (32%) were negative for all (TROP-2, NECTIN-4, PD-L1, HER-2, FGFR and pan-NTRK) biomarkers and 3 (11%) expressed all five biomarkers. Among cases with rhabdoid dedifferentiation, 1 of 7 (14%) showed activation of all biomarkers, whereas 2 of 7 (28%) showed none. The mRNA analysis identified microtubule-related genes and pathways suitable for combined ADC treatments in BUC. Conclusion: Sarcomatoid and rhabdoid BUC do harbor positive expression of the ADC targets TROP-2 or NECTIN-4 in a relatively modest subset of cases, whereas the majority do not. Different combinations of other positive biomarkers may help the choice of medical therapies. Overall, these findings have important clinical implications for targeted therapy for BUC.
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