title: Association of T-cell co-regulatory protein expression with clinical outcomes following radical cystectomy for urothelial carcinoma of the bladder.
abstract: OBJECTIVE
  Expression of T-cell co-regulatory proteins has been associated with worse outcomes in patients with UCB. We aimed to confirm these findings.
  
  
  METHODS
  The study comprised tissue microarrays from 302 consecutive UCB patients treated with RC and lymphadenectomy between 1988 and 2003, 117 matched lymph nodes, and 50 cases of adjacent normal urothelium controls, which were evaluated for B7-H1, B7-H3, and PD-1 protein expression by immunohistochemistry.
  
  
  RESULTS
  B7-H3 and PD-1 expression were increased in cancers compared to adjacent normal urothelium (58.6% vs 6% and 65% vs 0%, respectively; both p values < 0.001). Meanwhile, B7-H1 was expressed in 25% of cancers (n = 76). Expression of B7-H3, B7-H1, and PD-1 were highly correlated between the primary tumors and metastatic nodes, with concordance rates of 90%, 86%, and 78% for B7H3, B7H1 and PD-1, respectively. Expression was not associated with clinicopathologic features, disease recurrence, cancer-specific or overall mortality. However, for the subgroup of patients with organ-confined disease (n = 96), B7-H1 expression was associated with an increased risk of overall mortality (p = 0.02) on univariate and trended toward an association on multivariate analyses (p = 0.06).
  
  
  CONCLUSIONS
  B7-H1, B7-H3 and PD-1 are altered in a large proportion of UCB. B7-H1 and PD-1 expression are differentially upregulated in cancer versus normal urothelium. High correlation between expression in LN and expression in RC specimens was observed. While expression was not associated with clinicopathologic features or standard outcomes in all patients, B7-H1 expression predicted overall mortality after RC in the subset of patients with organ-confined UCB.
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, NY, USA; Inserm U955 Equipe 07, Université Paris Est Créteil, Créteil, France; Department of Urology, Cochin Hospital, APHP, Paris Descartes University, Paris, France.
authors.forename: E
authors.initials: E
authors.lastname: Xylinas
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Robinson
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: L A
authors.initials: LA
authors.lastname: Kluth
authors.affiliation: Department of Urology, Hospital Kassel, Kassel, Germany.
authors.forename: B G
authors.initials: BG
authors.lastname: Volkmer
authors.affiliation: Department of Urology, University Hospital Ulm, Ulm, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Hautmann
authors.affiliation: Department of Urology, Hospital am Eichert, Göppingen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Küfer
authors.affiliation: Department of Urology, Cochin Hospital, APHP, Paris Descartes University, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Zerbib
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: E
authors.initials: E
authors.lastname: Kwon
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Thompson
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Boorjian
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, NY, USA; Division of Medical Oncology, Weill Cornell Medical College, New York, NY, USA. Electronic address: sfs2002@med.cornell.edu.
authors.forename: S F
authors.initials: SF
authors.lastname: Shariat
mesh_terms: D000328:Adult; D000368:Aged; D060887:B7 Antigens / Q000032:analysis*; D060890:B7-H1 Antigen / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000378:metabolism / Q000401:mortality / Q000601:surgery*; D016022:Case-Control Studies; D015653:Cystectomy / Q000379:methods; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*; D046888:Tissue Array Analysis; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000401:mortality / Q000601:surgery*
chemical_list: D060887:B7 Antigens; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C423237:CD276 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Bladder cancer; Immunohistochemistry; Outcomes; Prognosis; Survival; T-cell regulators