Molecular profiling in muscle‐invasive bladder cancer: more than the sum of its parts
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,...
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Published in | The Journal of pathology Vol. 247; no. 5; pp. 563 - 573 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Chichester, UK
John Wiley & Sons, Ltd
01.04.2019
Wiley Subscription Services, Inc |
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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, 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. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
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AbstractList | 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. Copyright © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 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. |
Author | Jackson, Chelsea L Berman, David M Sjödahl, Gottfrid Bartlett, John MS Siemens, D Robert |
Author_xml | – sequence: 1 givenname: Gottfrid orcidid: 0000-0002-7869-0473 surname: Sjödahl fullname: Sjödahl, Gottfrid email: gottfrid.sjodahl@med.lu.se organization: Skåne University Hospital – sequence: 2 givenname: Chelsea L surname: Jackson fullname: Jackson, Chelsea L organization: Queen's University – sequence: 3 givenname: John MS surname: Bartlett fullname: Bartlett, John MS organization: Diagnostic Development Program, Ontario Institute for Cancer Research – sequence: 4 givenname: D Robert surname: Siemens fullname: Siemens, D Robert organization: Queen's University – sequence: 5 givenname: David M orcidid: 0000-0001-5985-3698 surname: Berman fullname: Berman, David M email: bermand@queensu.ca organization: Queen's University |
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Keywords | RB1 bladder neoplasms Shh cancer stem cell TGFB PPARG GATA3 KRT5 LUNDTAX TP53 |
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Snippet | Bladder cancers are biologically and clinically heterogeneous. Recent large‐scale transcriptomic profiling studies focusing on life‐threatening muscle‐invasive... Bladder cancers are biologically and clinically heterogeneous. Recent large-scale transcriptomic profiling studies focusing on life-threatening muscle-invasive... |
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SubjectTerms | Biomarkers, Tumor - metabolism Bladder cancer bladder neoplasms Breast cancer Cancer and Oncology Cancer och onkologi cancer stem cell Chemotherapy Clinical Medicine Cytostatic Agents - therapeutic use Cytotoxicity Epidermal growth factor receptors ErbB-2 protein Fibroblast growth factor receptors GATA3 Gene Expression Profiling - methods Gene Expression Regulation, Neoplastic Growth factors Heterogeneity Humans Immune checkpoint Immunohistochemistry Invasiveness Klinisk medicin KRT5 LUNDTAX Medical and Health Sciences Medicin och hälsovetenskap Muscle Neoplasms - genetics Muscle Neoplasms - pathology Muscles Mutation - genetics Neoplasm Invasiveness Neoplasm Metastasis Neoplasm Proteins - genetics PD-1 protein PPARG Prognosis RB1 Shh TGFB Therapeutic applications TP53 Urinary Bladder Neoplasms - drug therapy Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - pathology Urologi och njurmedicin Urology and Nephrology Workflow |
Title | Molecular profiling in muscle‐invasive bladder cancer: more than the sum of its parts |
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