Enhancer of zeste homolog 2 (EZH2) expression in bladder cancer

Joshua I Warrick, Jay D Raman, Matthew Kaag, Trey Bruggeman, Justin Cates, Peter Clark, David J DeGraff

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BACKGROUND: Studies evaluating enhancer of zeste homolog 2 (EZH2) expression and oncologic outcomes in bladder cancer have been discrepant. EZH2 expression in noninvasive bladder cancer is not well studied. We thus set out to address the discrepancy in previous reports, and to study expression of EZH2 in noninvasive bladder cancer and its associations, in a large cystectomy cohort.

MATERIALS AND METHODS: EZH2 expression was evaluated in tissue microarray material (invasive and noninvasive cancer). Associations between EZH2 expression and oncologic outcomes, tumor stage, and disease type were determined. Receiver operating characteristic analysis was performed for EZH2 expression in the diagnosis of invasive carcinoma and flat carcinoma in situ (CIS) compared to benign urothelium.

RESULTS: EZH2 expression was most common in CIS, followed by invasive carcinoma, noninvasive papillary urothelial carcinoma, and benign urothelium, in decreasing order (P<0.05 all comparisons, linear model). The receiver operating characteristic analysis demonstrated an area under the curve of 0.92 for CIS and 0.83 for invasive carcinoma, both compared to benign urothelium. At a cutoff of≥4, this corresponded to sensitivities of 89% and 73%, and specificities of 82% and 82%, for CIS and invasive carcinoma, respectively. The EZH2 expression was not associated with oncologic outcomes, including recurrence-free survival and death from bladder cancer. The EZH2 expression status (positive or negative) of noninvasive and invasive carcinomas taken from the same bladder correlated (P = 0.05, Fisher exact).

CONCLUSION: That EZH2 status of noninvasive and invasive cancer correlated in individual patients suggests that EZH2 may be a marker of lineage. EZH2 may offer diagnostic utility, particularly in flat urothelial CIS vs. benign urothelium. The present study supports that EZH2 expression in bladder cancer is not predictive of oncologic outcome.

OriginalsprogEngelsk
TidsskriftUrologic Oncology: Seminars and Original Investigations
Vol/bind34
Udgave nummer6
Sider (fra-til)258.e1-258.e6
ISSN1078-1439
DOI
StatusUdgivet - jun. 2016
Udgivet eksterntJa

Fingeraftryk

Urothelium
ROC Curve
Enhancer of Zeste Homolog 2 Protein
Neoplasms
Cystectomy
Area Under Curve
Linear Models

Citer dette

Warrick, J. I., Raman, J. D., Kaag, M., Bruggeman, T., Cates, J., Clark, P., & DeGraff, D. J. (2016). Enhancer of zeste homolog 2 (EZH2) expression in bladder cancer. Urologic Oncology: Seminars and Original Investigations, 34(6), 258.e1-258.e6. https://doi.org/10.1016/j.urolonc.2016.02.011
Warrick, Joshua I ; Raman, Jay D ; Kaag, Matthew ; Bruggeman, Trey ; Cates, Justin ; Clark, Peter ; DeGraff, David J. / Enhancer of zeste homolog 2 (EZH2) expression in bladder cancer. I: Urologic Oncology: Seminars and Original Investigations. 2016 ; Bind 34, Nr. 6. s. 258.e1-258.e6.
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title = "Enhancer of zeste homolog 2 (EZH2) expression in bladder cancer",
abstract = "BACKGROUND: Studies evaluating enhancer of zeste homolog 2 (EZH2) expression and oncologic outcomes in bladder cancer have been discrepant. EZH2 expression in noninvasive bladder cancer is not well studied. We thus set out to address the discrepancy in previous reports, and to study expression of EZH2 in noninvasive bladder cancer and its associations, in a large cystectomy cohort.MATERIALS AND METHODS: EZH2 expression was evaluated in tissue microarray material (invasive and noninvasive cancer). Associations between EZH2 expression and oncologic outcomes, tumor stage, and disease type were determined. Receiver operating characteristic analysis was performed for EZH2 expression in the diagnosis of invasive carcinoma and flat carcinoma in situ (CIS) compared to benign urothelium.RESULTS: EZH2 expression was most common in CIS, followed by invasive carcinoma, noninvasive papillary urothelial carcinoma, and benign urothelium, in decreasing order (P<0.05 all comparisons, linear model). The receiver operating characteristic analysis demonstrated an area under the curve of 0.92 for CIS and 0.83 for invasive carcinoma, both compared to benign urothelium. At a cutoff of≥4, this corresponded to sensitivities of 89{\%} and 73{\%}, and specificities of 82{\%} and 82{\%}, for CIS and invasive carcinoma, respectively. The EZH2 expression was not associated with oncologic outcomes, including recurrence-free survival and death from bladder cancer. The EZH2 expression status (positive or negative) of noninvasive and invasive carcinomas taken from the same bladder correlated (P = 0.05, Fisher exact).CONCLUSION: That EZH2 status of noninvasive and invasive cancer correlated in individual patients suggests that EZH2 may be a marker of lineage. EZH2 may offer diagnostic utility, particularly in flat urothelial CIS vs. benign urothelium. The present study supports that EZH2 expression in bladder cancer is not predictive of oncologic outcome.",
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Warrick, JI, Raman, JD, Kaag, M, Bruggeman, T, Cates, J, Clark, P & DeGraff, DJ 2016, 'Enhancer of zeste homolog 2 (EZH2) expression in bladder cancer', Urologic Oncology: Seminars and Original Investigations, bind 34, nr. 6, s. 258.e1-258.e6. https://doi.org/10.1016/j.urolonc.2016.02.011

Enhancer of zeste homolog 2 (EZH2) expression in bladder cancer. / Warrick, Joshua I; Raman, Jay D; Kaag, Matthew; Bruggeman, Trey; Cates, Justin; Clark, Peter; DeGraff, David J.

I: Urologic Oncology: Seminars and Original Investigations, Bind 34, Nr. 6, 06.2016, s. 258.e1-258.e6.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Enhancer of zeste homolog 2 (EZH2) expression in bladder cancer

AU - Warrick, Joshua I

AU - Raman, Jay D

AU - Kaag, Matthew

AU - Bruggeman, Trey

AU - Cates, Justin

AU - Clark, Peter

AU - DeGraff, David J

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/6

Y1 - 2016/6

N2 - BACKGROUND: Studies evaluating enhancer of zeste homolog 2 (EZH2) expression and oncologic outcomes in bladder cancer have been discrepant. EZH2 expression in noninvasive bladder cancer is not well studied. We thus set out to address the discrepancy in previous reports, and to study expression of EZH2 in noninvasive bladder cancer and its associations, in a large cystectomy cohort.MATERIALS AND METHODS: EZH2 expression was evaluated in tissue microarray material (invasive and noninvasive cancer). Associations between EZH2 expression and oncologic outcomes, tumor stage, and disease type were determined. Receiver operating characteristic analysis was performed for EZH2 expression in the diagnosis of invasive carcinoma and flat carcinoma in situ (CIS) compared to benign urothelium.RESULTS: EZH2 expression was most common in CIS, followed by invasive carcinoma, noninvasive papillary urothelial carcinoma, and benign urothelium, in decreasing order (P<0.05 all comparisons, linear model). The receiver operating characteristic analysis demonstrated an area under the curve of 0.92 for CIS and 0.83 for invasive carcinoma, both compared to benign urothelium. At a cutoff of≥4, this corresponded to sensitivities of 89% and 73%, and specificities of 82% and 82%, for CIS and invasive carcinoma, respectively. The EZH2 expression was not associated with oncologic outcomes, including recurrence-free survival and death from bladder cancer. The EZH2 expression status (positive or negative) of noninvasive and invasive carcinomas taken from the same bladder correlated (P = 0.05, Fisher exact).CONCLUSION: That EZH2 status of noninvasive and invasive cancer correlated in individual patients suggests that EZH2 may be a marker of lineage. EZH2 may offer diagnostic utility, particularly in flat urothelial CIS vs. benign urothelium. The present study supports that EZH2 expression in bladder cancer is not predictive of oncologic outcome.

AB - BACKGROUND: Studies evaluating enhancer of zeste homolog 2 (EZH2) expression and oncologic outcomes in bladder cancer have been discrepant. EZH2 expression in noninvasive bladder cancer is not well studied. We thus set out to address the discrepancy in previous reports, and to study expression of EZH2 in noninvasive bladder cancer and its associations, in a large cystectomy cohort.MATERIALS AND METHODS: EZH2 expression was evaluated in tissue microarray material (invasive and noninvasive cancer). Associations between EZH2 expression and oncologic outcomes, tumor stage, and disease type were determined. Receiver operating characteristic analysis was performed for EZH2 expression in the diagnosis of invasive carcinoma and flat carcinoma in situ (CIS) compared to benign urothelium.RESULTS: EZH2 expression was most common in CIS, followed by invasive carcinoma, noninvasive papillary urothelial carcinoma, and benign urothelium, in decreasing order (P<0.05 all comparisons, linear model). The receiver operating characteristic analysis demonstrated an area under the curve of 0.92 for CIS and 0.83 for invasive carcinoma, both compared to benign urothelium. At a cutoff of≥4, this corresponded to sensitivities of 89% and 73%, and specificities of 82% and 82%, for CIS and invasive carcinoma, respectively. The EZH2 expression was not associated with oncologic outcomes, including recurrence-free survival and death from bladder cancer. The EZH2 expression status (positive or negative) of noninvasive and invasive carcinomas taken from the same bladder correlated (P = 0.05, Fisher exact).CONCLUSION: That EZH2 status of noninvasive and invasive cancer correlated in individual patients suggests that EZH2 may be a marker of lineage. EZH2 may offer diagnostic utility, particularly in flat urothelial CIS vs. benign urothelium. The present study supports that EZH2 expression in bladder cancer is not predictive of oncologic outcome.

KW - Journal Article

U2 - 10.1016/j.urolonc.2016.02.011

DO - 10.1016/j.urolonc.2016.02.011

M3 - Journal article

VL - 34

SP - 258.e1-258.e6

JO - Urologic Oncology: Seminars and Original Investigations

JF - Urologic Oncology: Seminars and Original Investigations

SN - 1078-1439

IS - 6

ER -