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2008 Annual Meeting Abstracts
T-Cell Coregulatory Molecule Expression in Urothelial Cell Carcinoma: Clinicopathological Correlations and Association with Survival
Stephen A Boorjian*1, Yuri Sheinin*2, Paul L. Crispen*2, Sara A Farmer*2, Christine M Lohse*2, Susan M Kuntz*2, Bradley C Leibovich*2, Eugene D Kwon*2, Igor Frank*2
1Fox Chase Cancer Center, Philadelphia, PA;2Mayo Clinic, Rochester, MN
Introduction: 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 performed on paraffin-embedded sections from 318 consecutive patients with UCC who underwent radical cystectomy. Expression was correlated with clinicopathological outcomes and postoperative survival.
Results: B7-H3 was widely expressed in UCC, as 222/314 (70.7%) tumors demonstrated positive staining. Expression in UCC was significantly increased compared to adjacent, non-tumor urothelium, as a median of 70% of tumor cells expressed B7-H3, compared to 20% of cells in non-tumor 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 pathological stage. Patients who had received intravesical bacillus Calmette-Guerin prior to cystectomy tended to demonstrate 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). Among the subset of patients with organ-confined disease (n=167), moreover, B7-H1 expression predicted all-cause mortality following cystectomy (HR 2.18; 95% CI 1.26-3.77; p=0.005).
Conclusions: B7-H3 is highly expressed in UCC across tumor stages, while B7-H1 and PD-1 expression are associated with advanced disease. B7-H1 expression predicts mortality following 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.
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