The association and prognostic significance of B7-H3 with CD68+ tumor-associated macrophages in urothelial cell carcinoma

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Objective To investigate the expression of B7-H3 and the infiltration by CD68+ tumor-associated macrophages (TAMs) in urothelial cell carcinoma (UCC) of the bladder and evaluate its potential prognostic significance for bladder cancer. Methods Data from 76 consecutive UCC patients (63 males and 13 females), median age 65.5 years(ranging from 41 to 86 years), who underwent radical cystectomy, was collected. Immunohistochemistry for B7-H3 expression and CD68+ TAMs infiltration was performed on tumor tissues to explore their association with clinicopathologic features and postoperative survival. Results B7-H3 was widely expressed in UCC, as 54 of 76 (71.1%) tumors showed high expression of positive staining, and significantly increased compared with adjacent, nontumor urothelium (P<0.05). The B7-H3 expression and infiltration of CD68+ TAMs were independent of gender, age, tumor stage, grade, recurrence, lymphoid metastasis, yet both of them were markedly associated with distant metastasis of tumor(P=0.023; P=0.015). In addition, CD68+ TAMs infiltration and B7-H3 expression have significantly positive correlation (P=0.007). Furthermore, Kaplan-Meier analysis showed that overall survival and progression-free survival of patients with high B7-H3 expression was significantly worse than those with low B7-H3 expression (50 months vs. 70 months, P=0.004; 33 months vs. 59 months, P=0.006), while CD68+ TAMs infiltration was not independently associated with OS and PFS in the same cohort. But, in low CD68+ TAMs infiltration subgroup, the median OS and PFS in patients with high B7-H3 expression were shorter than patients with low B7-H3 expression (50 months vs. 68 months, P=0.034; 26 months vs. 59 months, P=0.024). Conclusions This study is the first report of B7-H3 expression and CD68+ TAMs infiltration in urothelial cell carcinoma of bladder in China. B7-H3 is highly expressed in UCC tissues, which could be used alone or in combination with CD68+ TAMs for assessing tumor progression after radical cystectomy. Therefor, these data indicate potentially important prognostic and therapeutic implications of B7-H3 and CD68+ TAMs for patients with UCC. Key words: B7-H3 genes; CD68 genes; Tumor-associated macrophages; Urothelial cell carcinoma; Survival analysis