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

Abstract

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.

• Authors: Evanguelos Xylinas, Eugene K Cha, Francesca Khani, Luis A Kluth, Malte Rieken, Björn G Volkmer, Richard Hautmann, Rainer Küfer, Yao-Tseng Chen, Marc Zerbib, Mark A Rubin, Douglas S Scherr, Shahrokh F Shariat, Brian D Robinson
• Journal: The Journal of urology (J Urol) Vol. 191 Issue 3 Pg. 830-41 (Mar 2014) ISSN: 1527-3792 [Electronic] United States
• PMID: 23994370 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, Neoplasm
• Antigens, Surface
• Biomarkers, Tumor
• Glypicans
• IGF2BP3 protein, human
• MAGEA3 protein, human
• Membrane Glycoproteins
• Neoplasm Proteins
• RNA-Binding Proteins

Topics

• Aged
• Antigens, Neoplasm (metabolism)
• Antigens, Surface (metabolism)
• Biomarkers, Tumor (metabolism)
• Carcinoma, Transitional Cell (metabolism, pathology, surgery)
• Cystectomy
• Glypicans (metabolism)
• Humans
• Lymph Node Excision
• Lymphatic Metastasis
• Membrane Glycoproteins (metabolism)
• Middle Aged
• Neoplasm Grading
• Neoplasm Proteins (metabolism)
• Neoplasm Staging
• RNA-Binding Proteins (metabolism)
• Treatment Outcome
• Urinary Bladder (metabolism, pathology, surgery)
• Urinary Bladder Neoplasms (metabolism, pathology, surgery)