Cox, Alexander and Kluemper, Niklas and Stein, Johannes and Sikic, Danijel and Breyer, Johannes and Bolenz, Christian and Roghmann, Florian and Erben, Philipp and Wirtz, Ralph M. and Wullich, Bernd and Ritter, Manuel and Hoelzel, Michael and Schwamborn, Kristina and Horn, Thomas and Gschwend, Juergen and Hartmann, Arndt and Weichert, Wilko and Erlmeier, Franziska and Eckstein, Markus (2024) Molecular Urothelial Tumor Cell Subtypes Remain Stable During Metastatic Evolution. EUROPEAN UROLOGY, 85 (4). pp. 328-332. ISSN 0302-2838, 1873-7560
Full text not available from this repository. (Request a copy)Abstract
Urothelial cancer (UC) care is moving toward precision oncology. For tumor biology-driven treatment of metastatic UC (mUC), molecular subtypes play a crucial role. However, it is not known whether subtypes change during metastatic evolution. To address this, we analyzed a UC progression cohort (N = 154 patients) with 138 matched primary tumors (PRIM) and synchronous or metachronous distant metastasis (MET) by immunohistochemistry, and mRNA sequencing in a subgroup of 20 matched pairs. Protein-based tumor cell subtypes and histomorphology remained stable during metastatic progression (concordance: 94%, 95% confidence interval [CI] 88-97%). In comparison, transcriptome-based molecular consensus subtypes exhibited higher heterogeneity between PRIM and MET (concordance: 45%, 95% CI 23-69%), with switches particularly occurring between luminal and stroma-rich tumors. Of note, all tumors classified as stroma rich showed luminal tumor cell differentiation. By an in-depth analysis, we found a negative correlation of luminal gene and protein expression with increasing desmoplastic stroma content, suggesting that luminal tumor cell differentiation of "stromarich tumors"is superimposed by gene expression signals stemming from the stromal compartment. Immunohistochemistry allows tumor cell subtyping into luminal, basal, or neuroendocrine classes that remain stable during metastatic progression. These findings expand our biological understanding of UC MET and have implications for future subtype-stratified clinical trials in patients with mUC. Patient summary: Urothelial carcinomas (UCs) occur in different appearances, the socalled molecular subtypes. These molecular subtypes will gain importance for the therapy of metastatic UCs in the future. We could demonstrate that the subtype remains stable during metastasis, which is highly relevant for future studies. (c) 2023 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Urothelial cancer; Metastatic urothelial carcinoma; Metastatic evolution; Subtypes; Molecular subtypes |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Urologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jan 2026 09:25 |
| Last Modified: | 22 Jan 2026 09:25 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65043 |
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