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Molecular pathology of the non-luminal Ba/Sq-like and Sc/NE-like classes of urothelial tumours : An integrated immunohistochemical analysis

Bernardo, Carina LU orcid ; Eriksson, Pontus LU ; Marzouka, Nour al dain LU ; Liedberg, Fredrik LU ; Sjödahl, Gottfrid LU and Höglund, Mattias LU (2022) In Human Pathology 122. p.11-24
Abstract

Several groups have during past years produced molecular classification schemes for bladder cancer. Even though no consensus on how to define a subtype exists, one approach has been to base definitions on how tumours cluster according to their mRNA expression profiles. In many cases, obtained profiles, and thus class defining features, are affected by signals from non-tumour cells within the biopsy. To overcome this issue, we combined gene expression analyses with analyses of the actual tumour cells by extensive immunohistochemistry (IHC). By this approach we were able to define tumour cell phenotypes i.e., subtypes defined by features of the tumour cells only, and adjust mRNA-based algorithms accordingly. In the present investigation... (More)

Several groups have during past years produced molecular classification schemes for bladder cancer. Even though no consensus on how to define a subtype exists, one approach has been to base definitions on how tumours cluster according to their mRNA expression profiles. In many cases, obtained profiles, and thus class defining features, are affected by signals from non-tumour cells within the biopsy. To overcome this issue, we combined gene expression analyses with analyses of the actual tumour cells by extensive immunohistochemistry (IHC). By this approach we were able to define tumour cell phenotypes i.e., subtypes defined by features of the tumour cells only, and adjust mRNA-based algorithms accordingly. In the present investigation we address the non-luminal Basal/Squamous-like (Ba/Sq) and Small cell/Neuroendocrine-like (Sc/NE) categories of tumours defined by mRNA-based classification. We make use of IHC data for 15 proteins, all known to be instrumental for defining molecular subtypes of urothelial carcinoma. We show that the UroB type of tumours, frequently grouped together with Ba/Sq, are different from the Ba/Sq entity at several essential features and is a derivative of Urothelial-like tumours (Uro). We show that the Sc/NE tumours are similar to but represents extreme versions of Genomically Unstable (GU) tumours. We apply clustering to 423 cases representing all subtypes using IHC data for 14 proteins and show that the obtained grouping conforms well with the mRNA-based classification. This work describes in detail the molecular pathology of non-luminal RNA-based bladder cancer subtypes and highlight similarities/dissimilarities suggestive of origin.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Basal/squamous, Bladder cancer, Classification, Immunohistochemistry, Lund taxonomy, Small cell neuroendocrine
in
Human Pathology
volume
122
pages
11 - 24
publisher
Elsevier
external identifiers
  • scopus:85125129149
  • pmid:35108518
ISSN
0046-8177
DOI
10.1016/j.humpath.2022.01.006
language
English
LU publication?
yes
additional info
Funding Information: This work was supported by the Swedish Research Council , the Gunnar Nilsson Cancer Foundation , the Mrs Berta Kamprad Foundation , the Swedish Cancer Society , Region Skåne ALF-funding , and Lund University, Skåne University Hospital Research Funds , Skåne County Council's Research and Development Foundation ( REGSKANE-821461 ), the Foundation of Urological Research (Ove and Carin Carlsson Bladder Cancer donation), and Hillevi Fries Research Foundation , and by BioCARE . Publisher Copyright: © 2022 The Author(s)
id
0dc802a1-e9b7-44a4-be7f-b0b0efc6986b
date added to LUP
2022-03-23 08:48:31
date last changed
2024-06-08 20:36:52
@article{0dc802a1-e9b7-44a4-be7f-b0b0efc6986b,
  abstract     = {{<p>Several groups have during past years produced molecular classification schemes for bladder cancer. Even though no consensus on how to define a subtype exists, one approach has been to base definitions on how tumours cluster according to their mRNA expression profiles. In many cases, obtained profiles, and thus class defining features, are affected by signals from non-tumour cells within the biopsy. To overcome this issue, we combined gene expression analyses with analyses of the actual tumour cells by extensive immunohistochemistry (IHC). By this approach we were able to define tumour cell phenotypes i.e., subtypes defined by features of the tumour cells only, and adjust mRNA-based algorithms accordingly. In the present investigation we address the non-luminal Basal/Squamous-like (Ba/Sq) and Small cell/Neuroendocrine-like (Sc/NE) categories of tumours defined by mRNA-based classification. We make use of IHC data for 15 proteins, all known to be instrumental for defining molecular subtypes of urothelial carcinoma. We show that the UroB type of tumours, frequently grouped together with Ba/Sq, are different from the Ba/Sq entity at several essential features and is a derivative of Urothelial-like tumours (Uro). We show that the Sc/NE tumours are similar to but represents extreme versions of Genomically Unstable (GU) tumours. We apply clustering to 423 cases representing all subtypes using IHC data for 14 proteins and show that the obtained grouping conforms well with the mRNA-based classification. This work describes in detail the molecular pathology of non-luminal RNA-based bladder cancer subtypes and highlight similarities/dissimilarities suggestive of origin.</p>}},
  author       = {{Bernardo, Carina and Eriksson, Pontus and Marzouka, Nour al dain and Liedberg, Fredrik and Sjödahl, Gottfrid and Höglund, Mattias}},
  issn         = {{0046-8177}},
  keywords     = {{Basal/squamous; Bladder cancer; Classification; Immunohistochemistry; Lund taxonomy; Small cell neuroendocrine}},
  language     = {{eng}},
  pages        = {{11--24}},
  publisher    = {{Elsevier}},
  series       = {{Human Pathology}},
  title        = {{Molecular pathology of the non-luminal Ba/Sq-like and Sc/NE-like classes of urothelial tumours : An integrated immunohistochemical analysis}},
  url          = {{http://dx.doi.org/10.1016/j.humpath.2022.01.006}},
  doi          = {{10.1016/j.humpath.2022.01.006}},
  volume       = {{122}},
  year         = {{2022}},
}