title: Association of oncofetal protein expression with clinical outcomes in patients with urothelial carcinoma of the bladder.
abstract: OBJECTIVE
  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.
  
  
  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.affiliation: Department of Urology, Weill Cornell Medical College, New York, New York; Institut National de la Santé et de la Recherche Médicale U955 Equipe 07, Université Paris-Est Créteil, Créteil, France; Department of Urology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris, France.
authors.forename: Evanguelos
authors.initials: E
authors.lastname: Xylinas
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, New York.
authors.forename: Eugene K
authors.initials: EK
authors.lastname: Cha
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Francesca
authors.initials: F
authors.lastname: Khani
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, New York; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Kluth
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, New York; Department of Urology, University Hospital Basel, Basel, Switzerland.
authors.forename: Malte
authors.initials: M
authors.lastname: Rieken
authors.affiliation: Department of Urology, Hospital Kassel, Kassel, Germany.
authors.forename: Björn G
authors.initials: BG
authors.lastname: Volkmer
authors.affiliation: Department of Urology, University Hospital Ulm, Ulm, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Hautmann
authors.affiliation: Department of Urology, Hospital am Eichert, Göppingen, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Küfer
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Yao-Tseng
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Department of Urology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris Descartes University, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Zerbib
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York; Institute for Precision Medicine of Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, New York.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Scherr
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, New York; Division of Medical Oncology, Weill Cornell Medical College, New York, New York; Department of Urology, Medical University of Vienna, Vienna, Austria. Electronic address: sfshariat@gmail.com.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, New York; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robinson
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015653:Cystectomy; D053673:Glypicans / Q000378:metabolism; D006801:Humans; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D016601:RNA-Binding Proteins / Q000378:metabolism; D016896:Treatment Outcome; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
chemical_list: D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; D053673:Glypicans; C498780:IGF2BP3 protein, human; C072013:MAGEA3 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins
keywords: carcinoma; oncofetal antigens; risk; urinary bladder; urothelium