Tumor cell and tumor vasculature expression of B7-H3 predict survival in clear cell renal cell carcinoma

Abstract

Purpose: Although the prognostic value of B7-H1 and B7-H4 expression by tumor cells in clear cell renal cell carcinoma (ccRCC) has been established, the role of B7-H3 is unknown. As such, we evaluated the association of B7-H3 expression with clinicopathologic outcomes in patients treated for ccRCC.

Experimental design: Nephrectomy specimens from 743 consecutive patients treated for ccRCC at our institution from 1990 to 1999 were evaluated for B7-H3 expression by immunohistochemical staining. Associations of B7-H3 expression with clinical and pathologic features were evaluated using chi2 and Fisher's exact tests. Associations of B7-H3 expression with death from RCC were evaluated using Cox proportional hazards regression models.

Results: B7-H3 expression by tumor cells or tumor vasculature was noted in 17% and 95% of specimens, respectively. The presence of either tumor cell or diffuse tumor vasculature expression of B7-H3 was present in 46% of specimens and was associated with multiple adverse clinical and pathologic features. After multivariable adjustment, the presence of either tumor cell or diffuse tumor vasculature B7-H3 expression was significantly associated with an increased risk of death from RCC (risk ratio, 1.38; 95% confidence interval, 1.03-1.84; P = 0.029).

Conclusions: Both tumor cell and tumor vasculature B7-H3 expression convey important information to predict ccRCC outcomes. Collectively, our past and present studies pertaining to B7-H ligand expression indicate that ccRCC may use redundant mechanisms to compromise host antitumoral immunity. Future studies will focus on the effect of combined B7-H ligand expression in RCC.

Fig. 1

Tumor cell and vasculature B7-H3 expression within ccRCC specimens. A, representative ccRCC tumor specimen with strong tumor cell B7-H3 immunohistochemical staining. B, ccRCC tumor specimen with negative tumor cell but sporadic tumor vasculature B7-H3 staining. C, blocking with B7-H3-Fc fusion protein completely abrogates staining of B7-H3–positive ccRCC tumor. Focal (D), moderate (E), or diffuse (F) tumor vasculature staining was observed in 31.9%, 26.5%, and 36.7%, respectively, of ccRCC tumor specimens studied. All photomicrographs, ×400.

Fig. 2

A, association of tumor cell B7-H3 expression with death from RCC. Cancer-specific survival rates (SE, number still at risk) at 5 and 10 y following surgery were 40.3% (4.5%, 44) and 29.8% (4.4%, 20), respectively, for patients with B7-H3–positive tumors compared with 81.0% (1.6%, 425) and 73.2% (2.0%, 200), respectively, for patients with B7-H3–negative tumors. B, association of tumor vasculature B7-H3 expression with death from RCC. Cancer-specific survival rates (SE, number still at risk) at 5 and 10 y following surgery were 88.2% (5.5%, 27) and 84.9% (6.2%, 9); 82.2% (2.6%, 159) and 78.6% (2.9%, 74); 79.0% (3.0%,134) and 64.2% (3.9%, 65); and 61.4% (3.0%, 149) and 53.8% (3.2%, 72) for patients with absent, focal, moderate, and diffuse tumor vasculature B7-H3 expression, respectively. C, association of either tumor cell or diffuse tumor vasculature B7-H3 expression with death from RCC. Cancer-specific survival rates (SE, number still at risk) at 5 and 10 y following surgery were 59.3% (2.7%, 177) and 50.2% (2.9%, 85), respectively, for patients with B7-H3–positive tumor cell or diffuse tumor vasculature B7-H3 expression compared with 86.5% (1.8%, 292) and 79.0% (2.3%, 135), respectively, for patients with B7-H3–negative tumor cell and absent, focal, or moderate tumor vasculature B7-H3 expression.