Abstract

Molecular subtyping may inform on prognosis and treatment response in bladder cancer. However, intratumoral molecular heterogeneity is not well studied in this disease and could complicate efforts to use molecular subtyping to guide patient management. To investigate intratumoral heterogeneity in bladder cancer, we examined molecular subtypes in a consecutive, retrospective cystectomy series of histologic variant bladder cancers and conventional urothelial carcinomas co-occurring with them. Molecular subtypes were assigned as per the approach reported by Lund University, an approach that incorporates cell cycle alterations and markers of differentiation, to give the urothelial-like, genomically unstable, basal-squamous, mesenchymal-like, and neuroendocrine-like subtypes. The majority (93%) of tumors were classified as urothelial like, genomically unstable, or basal squamous. Among patients with more than one tumor histology, 39% demonstrated molecular heterogeneity among the different tumor histologies. This was greatest for the basal-squamous subtype, 78% of which co-occurred with either urothelial-like or genomically unstable carcinoma (among cases with multiple histologies). In contrast, there was no co-occurrence of urothelial-like and genomically unstable carcinoma in the same patient. The findings indicate that bladder cancer is often molecularly heterogeneous, particularly in the basal-squamous subtype. This raises the concern for sampling error in laboratory tests that guide therapy based on molecular subtyping. Patient summary: In this report, we investigated molecular diversity among different areas from the same tumor in patients with bladder cancer. We found that different areas from the same tumor are often molecularly different. We conclude that this biological diversity must be taken into account when interpreting clinical molecular tests performed on bladder cancer samples. In bladder cancer, molecular subtype commonly differs between histologically distinct areas from the same tumor, most commonly in those with a component of the basal-squamous subtype. This suggests concern for sampling error in molecular tests based on molecular subtyping.

Original languageEnglish (US)
Pages (from-to)18-22
Number of pages5
JournalEuropean Urology
Volume75
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Urinary Bladder Neoplasms
Neoplasms
Histology
Selection Bias
Carcinoma
Cystectomy
Biodiversity
Differentiation Antigens
Cell Cycle
Therapeutics

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

@article{874209230f2349a4b42a6b45f0d00697,
title = "Intratumoral Heterogeneity of Bladder Cancer by Molecular Subtypes and Histologic Variants [Figure presented]",
abstract = "Molecular subtyping may inform on prognosis and treatment response in bladder cancer. However, intratumoral molecular heterogeneity is not well studied in this disease and could complicate efforts to use molecular subtyping to guide patient management. To investigate intratumoral heterogeneity in bladder cancer, we examined molecular subtypes in a consecutive, retrospective cystectomy series of histologic variant bladder cancers and conventional urothelial carcinomas co-occurring with them. Molecular subtypes were assigned as per the approach reported by Lund University, an approach that incorporates cell cycle alterations and markers of differentiation, to give the urothelial-like, genomically unstable, basal-squamous, mesenchymal-like, and neuroendocrine-like subtypes. The majority (93{\%}) of tumors were classified as urothelial like, genomically unstable, or basal squamous. Among patients with more than one tumor histology, 39{\%} demonstrated molecular heterogeneity among the different tumor histologies. This was greatest for the basal-squamous subtype, 78{\%} of which co-occurred with either urothelial-like or genomically unstable carcinoma (among cases with multiple histologies). In contrast, there was no co-occurrence of urothelial-like and genomically unstable carcinoma in the same patient. The findings indicate that bladder cancer is often molecularly heterogeneous, particularly in the basal-squamous subtype. This raises the concern for sampling error in laboratory tests that guide therapy based on molecular subtyping. Patient summary: In this report, we investigated molecular diversity among different areas from the same tumor in patients with bladder cancer. We found that different areas from the same tumor are often molecularly different. We conclude that this biological diversity must be taken into account when interpreting clinical molecular tests performed on bladder cancer samples. In bladder cancer, molecular subtype commonly differs between histologically distinct areas from the same tumor, most commonly in those with a component of the basal-squamous subtype. This suggests concern for sampling error in molecular tests based on molecular subtyping.",
author = "Joshua Warrick and Gottfrid Sj{\"o}dahl and Kaag, {Matthew G.} and Jay Raman and Suzanne Merrill and Lauren Shuman and Guoli Chen and Vonn Walter and David Degraff",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.eururo.2018.09.003",
language = "English (US)",
volume = "75",
pages = "18--22",
journal = "European Urology",
issn = "0302-2838",
publisher = "Elsevier",
number = "1",

}

Intratumoral Heterogeneity of Bladder Cancer by Molecular Subtypes and Histologic Variants [Figure presented]. / Warrick, Joshua; Sjödahl, Gottfrid; Kaag, Matthew G.; Raman, Jay; Merrill, Suzanne; Shuman, Lauren; Chen, Guoli; Walter, Vonn; Degraff, David.

In: European Urology, Vol. 75, No. 1, 01.01.2019, p. 18-22.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Intratumoral Heterogeneity of Bladder Cancer by Molecular Subtypes and Histologic Variants [Figure presented]

AU - Warrick, Joshua

AU - Sjödahl, Gottfrid

AU - Kaag, Matthew G.

AU - Raman, Jay

AU - Merrill, Suzanne

AU - Shuman, Lauren

AU - Chen, Guoli

AU - Walter, Vonn

AU - Degraff, David

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Molecular subtyping may inform on prognosis and treatment response in bladder cancer. However, intratumoral molecular heterogeneity is not well studied in this disease and could complicate efforts to use molecular subtyping to guide patient management. To investigate intratumoral heterogeneity in bladder cancer, we examined molecular subtypes in a consecutive, retrospective cystectomy series of histologic variant bladder cancers and conventional urothelial carcinomas co-occurring with them. Molecular subtypes were assigned as per the approach reported by Lund University, an approach that incorporates cell cycle alterations and markers of differentiation, to give the urothelial-like, genomically unstable, basal-squamous, mesenchymal-like, and neuroendocrine-like subtypes. The majority (93%) of tumors were classified as urothelial like, genomically unstable, or basal squamous. Among patients with more than one tumor histology, 39% demonstrated molecular heterogeneity among the different tumor histologies. This was greatest for the basal-squamous subtype, 78% of which co-occurred with either urothelial-like or genomically unstable carcinoma (among cases with multiple histologies). In contrast, there was no co-occurrence of urothelial-like and genomically unstable carcinoma in the same patient. The findings indicate that bladder cancer is often molecularly heterogeneous, particularly in the basal-squamous subtype. This raises the concern for sampling error in laboratory tests that guide therapy based on molecular subtyping. Patient summary: In this report, we investigated molecular diversity among different areas from the same tumor in patients with bladder cancer. We found that different areas from the same tumor are often molecularly different. We conclude that this biological diversity must be taken into account when interpreting clinical molecular tests performed on bladder cancer samples. In bladder cancer, molecular subtype commonly differs between histologically distinct areas from the same tumor, most commonly in those with a component of the basal-squamous subtype. This suggests concern for sampling error in molecular tests based on molecular subtyping.

AB - Molecular subtyping may inform on prognosis and treatment response in bladder cancer. However, intratumoral molecular heterogeneity is not well studied in this disease and could complicate efforts to use molecular subtyping to guide patient management. To investigate intratumoral heterogeneity in bladder cancer, we examined molecular subtypes in a consecutive, retrospective cystectomy series of histologic variant bladder cancers and conventional urothelial carcinomas co-occurring with them. Molecular subtypes were assigned as per the approach reported by Lund University, an approach that incorporates cell cycle alterations and markers of differentiation, to give the urothelial-like, genomically unstable, basal-squamous, mesenchymal-like, and neuroendocrine-like subtypes. The majority (93%) of tumors were classified as urothelial like, genomically unstable, or basal squamous. Among patients with more than one tumor histology, 39% demonstrated molecular heterogeneity among the different tumor histologies. This was greatest for the basal-squamous subtype, 78% of which co-occurred with either urothelial-like or genomically unstable carcinoma (among cases with multiple histologies). In contrast, there was no co-occurrence of urothelial-like and genomically unstable carcinoma in the same patient. The findings indicate that bladder cancer is often molecularly heterogeneous, particularly in the basal-squamous subtype. This raises the concern for sampling error in laboratory tests that guide therapy based on molecular subtyping. Patient summary: In this report, we investigated molecular diversity among different areas from the same tumor in patients with bladder cancer. We found that different areas from the same tumor are often molecularly different. We conclude that this biological diversity must be taken into account when interpreting clinical molecular tests performed on bladder cancer samples. In bladder cancer, molecular subtype commonly differs between histologically distinct areas from the same tumor, most commonly in those with a component of the basal-squamous subtype. This suggests concern for sampling error in molecular tests based on molecular subtyping.

UR - http://www.scopus.com/inward/record.url?scp=85053884922&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053884922&partnerID=8YFLogxK

U2 - 10.1016/j.eururo.2018.09.003

DO - 10.1016/j.eururo.2018.09.003

M3 - Article

C2 - 30266310

AN - SCOPUS:85053884922

VL - 75

SP - 18

EP - 22

JO - European Urology

JF - European Urology

SN - 0302-2838

IS - 1

ER -