Blute, Michael L.

Abstract B7x is the newest member of the B7-CD28 family and is thought to dampen immune responses via negative costimulation. Tumor expression of B7x was recently described in renal cell carcinoma (RCC) and was associated with poor outcome. We developed an assay to detect serum-soluble B7x (sB7x) and investigated 101 patients with clear cell RCC who underwent nephrectomy between 2003 and 2007. For controls, we obtained serum from 101 sex-matched blood donors within the same age range. Following an ELISA for sB7x, detectable levels (>0.1 ng/mL) of sB7x were observed in 53 RCC patients compared with 18 controls (P < 0.001). Median (range) concentrations of sB7x for RCC patients and controls were 14.4 ng/mL (0.1–56.9) and 2.7 ng/mL (0.2–37.1), respectively. For RCC patients with detectable sB7x, median levels were significantly higher for patients with a tumor thrombus (19.2 versus 6.6 ng/mL; P = 0.007), positive lymph nodes (41.3 versus 10.3 ng/mL; P = 0.018), and distant metastases at nephrectomy (43.3 versus 8.5 ng/mL; P = 0.002) and tended to be higher in patients with high-grade tumors (18.8 versus 8.5; P = 0.090). Additionally, median sB7x levels for tumor-node-metastasis stage I to IV RCC were 6.6, 10.3, 14.5, and 43.3 ng/mL, respectively (P = 0.012). In this first evaluation of sB7x in RCC, we show that RCC patients are more likely to have detectable sB7x compared with controls and higher sB7x levels correlate with advanced tumor stage. These early results merit further investigation of this serum marker for potential diagnostic and prognostic purposes. [Cancer Res 2008;68(15):6054–8]

A significant increase in the incidental detection of small renal tumors has been observed with the routine use of cross-sectional abdominal imaging. However, the proportion of small renal tumors associated with multifocal RCC has yet to be established. Here then, we report our experience with the treatment of multifocal RCC in which the primary tumor was ≤4 cm. In our series of 1113 RCC patients, 5.4% (60/1113) had multifocal disease at the time of nephrectomy. Discordant histology was present in 17% (10/60) of patients with multifocal RCC. Nephron sparing surgery was utilized more frequently in patients with solitary tumors. Overall, cancer-specific, and distant metastasis-free survival appeared to be similar between multifocal and solitary tumors. These findings are consistent with previous series which evaluated multifocal RCC with tumors >4 cm. With the known incidence of multifocality RCC, careful inspection of the entire renal unit should be performed when performing nephron sparing surgery.