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Molecular profiling in muscle-invasive bladder cancer : more than the sum of its parts

Sjödahl, Gottfrid LU ; Jackson, Chelsea L. ; Bartlett, John M.S. ; Siemens, D. Robert and Berman, David M. (2019) In Journal of Pathology 247(5). p.563-573
Abstract

Bladder cancers are biologically and clinically heterogeneous. Recent large-scale transcriptomic profiling studies focusing on life-threatening muscle-invasive cases have demonstrated a small number of molecularly distinct clusters that largely explain their heterogeneity. Similar to breast cancer, these clusters reflect intrinsic urothelial cell-type differentiation programs, including those with luminal and basal cell characteristics. Also like breast cancer, each cell-based subtype demonstrates a distinct profile with regard to its prognosis and its expression of therapeutic targets. Indeed, a number of studies suggest subtype-specific differential responses to cytotoxic chemotherapy and to therapies that inhibit a number of targets,... (More)

Bladder cancers are biologically and clinically heterogeneous. Recent large-scale transcriptomic profiling studies focusing on life-threatening muscle-invasive cases have demonstrated a small number of molecularly distinct clusters that largely explain their heterogeneity. Similar to breast cancer, these clusters reflect intrinsic urothelial cell-type differentiation programs, including those with luminal and basal cell characteristics. Also like breast cancer, each cell-based subtype demonstrates a distinct profile with regard to its prognosis and its expression of therapeutic targets. Indeed, a number of studies suggest subtype-specific differential responses to cytotoxic chemotherapy and to therapies that inhibit a number of targets, including growth factors (EGFR, ERBB2, FGFR) and immune checkpoint (PD1, PDL1) inhibitors. Despite burgeoning evidence for important clinical implications, subtyping has yet to enter into routine clinical practice. Here we review the conceptual basis for intrinsic cell subtyping in muscle-invasive bladder cancer and discuss evidence behind proposed clinical uses for subtyping as a prognostic or predictive test. In deliberating barriers to clinical implementation, we review pitfalls associated with transcriptomic profiling and illustrate a simple immunohistochemistry (IHC)-based subtyping algorithm that may serve as a faster, less expensive alternative. Envisioned as a research tool that can easily be translated into routine pathology workflow, IHC-based profiling has the potential to more rapidly establish the utility (or lack thereof) of cell type profiling in clinical practice.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bladder neoplasms, cancer stem cell, GATA3, KRT5, LUNDTAX, PPARG, RB1, Shh, TGFB, TP53
in
Journal of Pathology
volume
247
issue
5
pages
563 - 573
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:30604486
  • scopus:85061917639
ISSN
0022-3417
DOI
10.1002/path.5230
language
English
LU publication?
yes
id
1643b9c7-92c6-43dd-9a10-11bb612ab5c6
date added to LUP
2019-03-04 09:48:29
date last changed
2024-06-11 05:36:55
@article{1643b9c7-92c6-43dd-9a10-11bb612ab5c6,
  abstract     = {{<p>Bladder cancers are biologically and clinically heterogeneous. Recent large-scale transcriptomic profiling studies focusing on life-threatening muscle-invasive cases have demonstrated a small number of molecularly distinct clusters that largely explain their heterogeneity. Similar to breast cancer, these clusters reflect intrinsic urothelial cell-type differentiation programs, including those with luminal and basal cell characteristics. Also like breast cancer, each cell-based subtype demonstrates a distinct profile with regard to its prognosis and its expression of therapeutic targets. Indeed, a number of studies suggest subtype-specific differential responses to cytotoxic chemotherapy and to therapies that inhibit a number of targets, including growth factors (EGFR, ERBB2, FGFR) and immune checkpoint (PD1, PDL1) inhibitors. Despite burgeoning evidence for important clinical implications, subtyping has yet to enter into routine clinical practice. Here we review the conceptual basis for intrinsic cell subtyping in muscle-invasive bladder cancer and discuss evidence behind proposed clinical uses for subtyping as a prognostic or predictive test. In deliberating barriers to clinical implementation, we review pitfalls associated with transcriptomic profiling and illustrate a simple immunohistochemistry (IHC)-based subtyping algorithm that may serve as a faster, less expensive alternative. Envisioned as a research tool that can easily be translated into routine pathology workflow, IHC-based profiling has the potential to more rapidly establish the utility (or lack thereof) of cell type profiling in clinical practice.</p>}},
  author       = {{Sjödahl, Gottfrid and Jackson, Chelsea L. and Bartlett, John M.S. and Siemens, D. Robert and Berman, David M.}},
  issn         = {{0022-3417}},
  keywords     = {{bladder neoplasms; cancer stem cell; GATA3; KRT5; LUNDTAX; PPARG; RB1; Shh; TGFB; TP53}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{5}},
  pages        = {{563--573}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Journal of Pathology}},
  title        = {{Molecular profiling in muscle-invasive bladder cancer : more than the sum of its parts}},
  url          = {{http://dx.doi.org/10.1002/path.5230}},
  doi          = {{10.1002/path.5230}},
  volume       = {{247}},
  year         = {{2019}},
}