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Molecular subtype classification of urothelial carcinoma in Lynch syndrome

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Therkildsen, C, Eriksson, P, Höglund, M, Jönsson, M, Sjödahl, G, Nilbert, M & Liedberg, F 2018, 'Molecular subtype classification of urothelial carcinoma in Lynch syndrome', Molecular Oncology, bind 12, nr. 8, s. 1286-1295. https://doi.org/10.1002/1878-0261.12325

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Therkildsen, Christina ; Eriksson, Pontus ; Höglund, Mattias ; Jönsson, Mats ; Sjödahl, Gottfrid ; Nilbert, Mef ; Liedberg, Fredrik. / Molecular subtype classification of urothelial carcinoma in Lynch syndrome. I: Molecular Oncology. 2018 ; Bind 12, Nr. 8. s. 1286-1295.

Bibtex

@article{560ce512c41c4f5c9076f5cc1e2e5292,
title = "Molecular subtype classification of urothelial carcinoma in Lynch syndrome",
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 UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis 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 Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was 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 data sets revealed that Lynch syndrome-associated UC share 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. This article is protected by copyright. All rights reserved.",
author = "Christina Therkildsen and Pontus Eriksson and Mattias H{\"o}glund and Mats J{\"o}nsson and Gottfrid Sj{\"o}dahl and Mef Nilbert and Fredrik Liedberg",
note = "Molecular Oncology (2018) {\textcopyright} 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.",
year = "2018",
month = aug,
day = "1",
doi = "10.1002/1878-0261.12325",
language = "English",
volume = "12",
pages = "1286--1295",
journal = "Molecular Oncology",
issn = "1574-7891",
publisher = "Elsevier BV",
number = "8",

}

RIS

TY - JOUR

T1 - Molecular subtype classification of urothelial carcinoma in Lynch syndrome

AU - Therkildsen, Christina

AU - Eriksson, Pontus

AU - Höglund, Mattias

AU - Jönsson, Mats

AU - Sjödahl, Gottfrid

AU - Nilbert, Mef

AU - Liedberg, Fredrik

N1 - Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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 UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis 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 Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was 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 data sets revealed that Lynch syndrome-associated UC share 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. This article is protected by copyright. All rights reserved.

AB - 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 UC of the upper urinary tract and the urinary bladder were identified in the Danish hereditary non-polyposis 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 Lynch syndrome patients were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data was 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 data sets revealed that Lynch syndrome-associated UC share 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. This article is protected by copyright. All rights reserved.

U2 - 10.1002/1878-0261.12325

DO - 10.1002/1878-0261.12325

M3 - Journal article

C2 - 29791078

VL - 12

SP - 1286

EP - 1295

JO - Molecular Oncology

JF - Molecular Oncology

SN - 1574-7891

IS - 8

ER -

ID: 54585574