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Metastasis and recurrence patterns in the molecular subtypes of urothelial bladder cancer

Sjödahl, Gottfrid LU ; Eriksson, Pontus LU ; Holmsten, Karin ; Abrahamsson, Johan LU ; Höglund, Mattias LU ; Bernardo, Carina LU orcid ; Ullén, Anders and Liedberg, Fredrik LU (2024) In International Journal of Cancer 154(1). p.180-190
Abstract

Urothelial cancer of the urinary bladder frequently metastasizes to lymph-nodes, lungs, liver and bone. A taxonomy for molecular classification exists, but it is unknown if molecular subtypes show tropism for different organs. Here, we study 146 patients with de novo metastatic disease or recurrence after curative treatment. We classify primary tumors using two transcriptomic methods and immunostaining and identify enrichment and depletion of metastatic sites in molecular subtypes using permutation tests. We observed significant depletion of bone metastases in the Basal/squamous molecular subtype, whereas the Urothelial-like subtype entailed an enrichment for metastases to bone. The Genomically unstable subtype was depleted of lung... (More)

Urothelial cancer of the urinary bladder frequently metastasizes to lymph-nodes, lungs, liver and bone. A taxonomy for molecular classification exists, but it is unknown if molecular subtypes show tropism for different organs. Here, we study 146 patients with de novo metastatic disease or recurrence after curative treatment. We classify primary tumors using two transcriptomic methods and immunostaining and identify enrichment and depletion of metastatic sites in molecular subtypes using permutation tests. We observed significant depletion of bone metastases in the Basal/squamous molecular subtype, whereas the Urothelial-like subtype entailed an enrichment for metastases to bone. The Genomically unstable subtype was depleted of lung metastases, but enriched for atypical sites, including six out of seven patients with brain metastases. Stroma-rich primary tumor samples were associated with local recurrence, but not with distant sites. Additionally, the proportion with brain or testis metastases differed between systemic chemotherapy regimens (GC vs MVAC) suggesting a sanctuary effect. In conclusion, molecular subtypes of urothelial bladder cancer are significantly associated with specific metastatic sites, suggesting that subtype-specific molecular determinants could exist at various steps in the metastatic cascade.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bladder cancer, metastasis, molecular subtypes, organotropism, urothelial carcinoma
in
International Journal of Cancer
volume
154
issue
1
pages
180 - 190
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:37671617
  • scopus:85169840874
ISSN
0020-7136
DOI
10.1002/ijc.34715
language
English
LU publication?
yes
id
56038f04-8b10-4134-8920-f1b9dcb99a18
date added to LUP
2023-11-03 11:19:03
date last changed
2025-05-03 15:02:28
@article{56038f04-8b10-4134-8920-f1b9dcb99a18,
  abstract     = {{<p>Urothelial cancer of the urinary bladder frequently metastasizes to lymph-nodes, lungs, liver and bone. A taxonomy for molecular classification exists, but it is unknown if molecular subtypes show tropism for different organs. Here, we study 146 patients with de novo metastatic disease or recurrence after curative treatment. We classify primary tumors using two transcriptomic methods and immunostaining and identify enrichment and depletion of metastatic sites in molecular subtypes using permutation tests. We observed significant depletion of bone metastases in the Basal/squamous molecular subtype, whereas the Urothelial-like subtype entailed an enrichment for metastases to bone. The Genomically unstable subtype was depleted of lung metastases, but enriched for atypical sites, including six out of seven patients with brain metastases. Stroma-rich primary tumor samples were associated with local recurrence, but not with distant sites. Additionally, the proportion with brain or testis metastases differed between systemic chemotherapy regimens (GC vs MVAC) suggesting a sanctuary effect. In conclusion, molecular subtypes of urothelial bladder cancer are significantly associated with specific metastatic sites, suggesting that subtype-specific molecular determinants could exist at various steps in the metastatic cascade.</p>}},
  author       = {{Sjödahl, Gottfrid and Eriksson, Pontus and Holmsten, Karin and Abrahamsson, Johan and Höglund, Mattias and Bernardo, Carina and Ullén, Anders and Liedberg, Fredrik}},
  issn         = {{0020-7136}},
  keywords     = {{bladder cancer; metastasis; molecular subtypes; organotropism; urothelial carcinoma}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{180--190}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{International Journal of Cancer}},
  title        = {{Metastasis and recurrence patterns in the molecular subtypes of urothelial bladder cancer}},
  url          = {{http://dx.doi.org/10.1002/ijc.34715}},
  doi          = {{10.1002/ijc.34715}},
  volume       = {{154}},
  year         = {{2024}},
}