Association of oncofetal protein expression with clinical outcomes in patients with urothelial carcinoma of the bladder

TY - JOUR

T1 - Association of oncofetal protein expression with clinical outcomes in patients with urothelial carcinoma of the bladder

AU - Xylinas, Evanguelos

AU - Cha, Eugene K

AU - Khani, Francesca

AU - Kluth, Luis A

AU - Rieken, Malte

AU - Volkmer, Björn G

AU - Hautmann, Richard

AU - Küfer, Rainer

AU - Chen, Yao-Tseng

AU - Zerbib, Marc

AU - Rubin, Mark A

AU - Scherr, Douglas S

AU - Shariat, Shahrokh F

AU - Robinson, Brian D

N1 - Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

PY - 2014/3/1

Y1 - 2014/3/1

N2 - PURPOSE: Oncofetal proteins are expressed in the developing embryo. Oncofetal protein expression correlates with the clinical outcome of nonmuscle invasive bladder urothelial carcinoma. IMP3, MAGE-A, glypican-3 and TPBG are oncofetal proteins that have not been well characterized in urothelial carcinoma of the bladder.MATERIALS AND METHODS: We investigated the expression of these 4 proteins and their association with clinical outcomes using tissue microarrays from 384 consecutive patients treated with radical cystectomy between 1988 and 2003 at 1 academic center. We stained for IMP3, MAGE-A, glypican-3 and TPBG. Univariable and multivariable Cox regression analyses were done to evaluate the association of oncofetal protein expression with disease recurrence and cancer specific mortality.RESULTS: IMP3, MAGE-A, glypican-3 and TPBG were expressed in 39.5%, 45%, 6% and 85% of urothelial bladder carcinomas, respectively. Expression was tumor specific and did not correlate with pathological features except for TPBG. At a median followup of 128 months 176 patients (46%) experienced disease recurrence, 175 (45.5%) had died of the disease and 96 (27.5%) had died of another cause. On univariable analysis IMP3 and MAGE-A expression was associated with an increased risk of disease recurrence (p <0.001 and 0.03) and cancer specific mortality (p = 0.004 and 0.03, respectively). On multivariable Cox regression analysis adjusted for the effects of standard clinicopathological features IMP3 and MAGE-A expression was independently associated with disease recurrence (p = 0.004, HR 1.55, 95% CI 1.15-2.11 and p = 0.02, HR 1.44, 95% CI 1.05-1.99, respectively) but not with cancer specific mortality.CONCLUSIONS: Oncofetal proteins are commonly and differentially expressed in urothelial carcinoma of the bladder compared to normal urothelium. IMP3 and MAGE-A expression was associated with disease recurrence and cancer specific mortality but glypican-3 and TPBG expression was not.

AB - PURPOSE: Oncofetal proteins are expressed in the developing embryo. Oncofetal protein expression correlates with the clinical outcome of nonmuscle invasive bladder urothelial carcinoma. IMP3, MAGE-A, glypican-3 and TPBG are oncofetal proteins that have not been well characterized in urothelial carcinoma of the bladder.MATERIALS AND METHODS: We investigated the expression of these 4 proteins and their association with clinical outcomes using tissue microarrays from 384 consecutive patients treated with radical cystectomy between 1988 and 2003 at 1 academic center. We stained for IMP3, MAGE-A, glypican-3 and TPBG. Univariable and multivariable Cox regression analyses were done to evaluate the association of oncofetal protein expression with disease recurrence and cancer specific mortality.RESULTS: IMP3, MAGE-A, glypican-3 and TPBG were expressed in 39.5%, 45%, 6% and 85% of urothelial bladder carcinomas, respectively. Expression was tumor specific and did not correlate with pathological features except for TPBG. At a median followup of 128 months 176 patients (46%) experienced disease recurrence, 175 (45.5%) had died of the disease and 96 (27.5%) had died of another cause. On univariable analysis IMP3 and MAGE-A expression was associated with an increased risk of disease recurrence (p <0.001 and 0.03) and cancer specific mortality (p = 0.004 and 0.03, respectively). On multivariable Cox regression analysis adjusted for the effects of standard clinicopathological features IMP3 and MAGE-A expression was independently associated with disease recurrence (p = 0.004, HR 1.55, 95% CI 1.15-2.11 and p = 0.02, HR 1.44, 95% CI 1.05-1.99, respectively) but not with cancer specific mortality.CONCLUSIONS: Oncofetal proteins are commonly and differentially expressed in urothelial carcinoma of the bladder compared to normal urothelium. IMP3 and MAGE-A expression was associated with disease recurrence and cancer specific mortality but glypican-3 and TPBG expression was not.

KW - Aged

KW - Antigens, Neoplasm

KW - Antigens, Surface

KW - Carcinoma, Transitional Cell

KW - Cystectomy

KW - Glypicans

KW - Humans

KW - Lymph Node Excision

KW - Lymphatic Metastasis

KW - Membrane Glycoproteins

KW - Middle Aged

KW - Neoplasm Grading

KW - Neoplasm Proteins

KW - Neoplasm Staging

KW - RNA-Binding Proteins

KW - Treatment Outcome

KW - Tumor Markers, Biological

KW - Urinary Bladder

KW - Urinary Bladder Neoplasms

U2 - 10.1016/j.juro.2013.08.048

DO - 10.1016/j.juro.2013.08.048

M3 - SCORING: Journal article

C2 - 23994370

VL - 191

SP - 830

EP - 841

JO - J UROLOGY

JF - J UROLOGY

SN - 0022-5347

IS - 3

ER -