title: T-cell coregulatory molecule expression in urothelial cell carcinoma: clinicopathologic correlations and association with survival.
abstract: OBJECTIVE
  Aberrant expression of T-cell coregulatory molecules has been investigated as a mechanism by which certain cancers may evade host immune surveillance. We evaluated expression of the T-cell coregulators B7-H1, B7-H3, and PD-1 in urothelial cell carcinoma (UCC) of the bladder.
  
  
  METHODS
  Immunohistochemistry for B7-H1, B7-H3, and PD-1 was done on paraffin-embedded sections from 318 consecutive patients with UCC who underwent radical cystectomy. Expression was correlated with clinicopathologic outcomes and postoperative survival.
  
  
  RESULTS
  B7-H3 was widely expressed in UCC, as 222 of 314 (70.7%) tumors showed positive staining. Expression of B7-H3 in UCC was significantly increased compared with adjacent, nontumor urothelium, as a median of 70% of tumor cells expressed B7-H3, compared with 20% of cells in nontumor specimens (P < 0.001). The increase in B7-H3 expression was independent of tumor stage (P = 0.13). Expression of B7-H1 by UCC tumors (P < 0.001) and PD-1 by tumor-infiltrating lymphocytes (P = 0.012) were significantly associated with increased pathologic stage. Patients who had received intravesical bacillus Calmette-Guerin before cystectomy tended to show increased expression of B7-H3 (P = 0.023) and PD-1 (P = 0.071) but were less likely to express B7-H1 (P = 0.027). Moreover, for the subset of patients with organ-confined disease (n = 167), B7-H1 expression independently predicted all-cause mortality after cystectomy (hazard ratio, 3.18; 95% confidence interval, 1.74-5.79; P < 0.001).
  
  
  CONCLUSIONS
  B7-H3 is highly expressed in UCC across tumor stages, whereas B7-H1 and PD-1 expression are associated with advanced disease. B7-H1 expression predicts mortality after cystectomy for patients with organ-confined tumors. These molecules may represent novel diagnostic or prognostic markers, as well as therapeutic targets, for patients with UCC.
authors.affiliation: Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Boorjian
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sheinin
authors.forename: Paul L
authors.initials: PL
authors.lastname: Crispen
authors.forename: Sara A
authors.initials: SA
authors.lastname: Farmer
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lohse
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kuntz
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Leibovich
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Kwon
authors.forename: Igor
authors.initials: I
authors.lastname: Frank
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000096:biosynthesis*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D060887:B7 Antigens; D060890:B7-H1 Antigen; D002277:Carcinoma / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060887:B7 Antigens; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C423237:CD276 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic