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Molecular subtype classification of urothelial carcinoma in Lynch syndrome

Therkildsen, Christina LU ; Eriksson, Pontus LU ; Höglund, Mattias LU ; Jönsson, Mats LU ; Sjödahl, Gottfrid LU ; Nilbert, Mef LU and Liedberg, Fredrik LU (2018) In Molecular Oncology 12(8). p.1286-1295
Abstract

Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UCs of the upper urinary tract and the urinary bladder were identified in the Danish hereditary nonpolyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole-genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A... (More)

Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UCs of the upper urinary tract and the urinary bladder were identified in the Danish hereditary nonpolyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole-genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from patients with Lynch syndrome were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data were analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as urothelial-like tumors with only 20% being genomically unstable, basal/SCC-like, or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger datasets revealed that Lynch syndrome-associated UC shares molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
bladder cancer, lynch syndrome, upper urinary tract urothelial carcinoma, urothelial carcinoma
in
Molecular Oncology
volume
12
issue
8
pages
10 pages
publisher
Elsevier
external identifiers
  • scopus:85050958143
ISSN
1574-7891
DOI
10.1002/1878-0261.12325
language
English
LU publication?
yes
id
3484cde4-ee55-49dd-9762-4a757b961511
date added to LUP
2018-08-22 12:07:38
date last changed
2019-02-24 04:52:26
@article{3484cde4-ee55-49dd-9762-4a757b961511,
  abstract     = {<p>Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UCs of the upper urinary tract and the urinary bladder were identified in the Danish hereditary nonpolyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole-genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from patients with Lynch syndrome were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data were analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as urothelial-like tumors with only 20% being genomically unstable, basal/SCC-like, or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger datasets revealed that Lynch syndrome-associated UC shares molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset.</p>},
  author       = {Therkildsen, Christina and Eriksson, Pontus and Höglund, Mattias and Jönsson, Mats and Sjödahl, Gottfrid and Nilbert, Mef and Liedberg, Fredrik},
  issn         = {1574-7891},
  keyword      = {bladder cancer,lynch syndrome,upper urinary tract urothelial carcinoma,urothelial carcinoma},
  language     = {eng},
  month        = {08},
  number       = {8},
  pages        = {1286--1295},
  publisher    = {Elsevier},
  series       = {Molecular Oncology},
  title        = {Molecular subtype classification of urothelial carcinoma in Lynch syndrome},
  url          = {http://dx.doi.org/10.1002/1878-0261.12325},
  volume       = {12},
  year         = {2018},
}