T-Cell coregulatory molecule expression in urothelial cell carcinoma: clinicopathologic correlations and association with survival

Stephen A. Boorjian, Yuri Sheinin, Paul L. Crispen, Sara A. Farmer, Christine M. Lohse, Susan M. Kuntz, Bradley C. Leibovich, Eugene D. Kwon, Igor Frank

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182 Scopus citations

Abstract

Purpose: 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. Experimental Design: lmmunohistochemistryfor B7-H1, B7-H3, and PD-1 was done on paraffinembedded 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 tumorinfiltrating 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.

Original languageEnglish (US)
Pages (from-to)4800-4808
Number of pages9
JournalClinical Cancer Research
Volume14
Issue number15
DOIs
StatePublished - Aug 1 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Boorjian, S. A., Sheinin, Y., Crispen, P. L., Farmer, S. A., Lohse, C. M., Kuntz, S. M., Leibovich, B. C., Kwon, E. D., & Frank, I. (2008). T-Cell coregulatory molecule expression in urothelial cell carcinoma: clinicopathologic correlations and association with survival. Clinical Cancer Research, 14(15), 4800-4808. https://doi.org/10.1158/1078-0432.CCR-08-0731