Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma
R Houston Thompson, Michael D Gillett, John C Cheville, Christine M Lohse, Haidong Dong, W Scott Webster, Lieping Chen, Horst Zincke, Michael L Blute, Bradley C Leibovich, Eugene D Kwon, R Houston Thompson, Michael D Gillett, John C Cheville, Christine M Lohse, Haidong Dong, W Scott Webster, Lieping Chen, Horst Zincke, Michael L Blute, Bradley C Leibovich, Eugene D Kwon
Abstract
Background: Cancer cell expression of costimulatory molecule B7-H1 has been implicated as a potent inhibitor of T-cell-mediated antitumoral immunity. The authors recently reported that B7-H1 is aberrantly expressed in primary renal cell carcinoma (RCC). Blockade of B7-H1, as demonstrated in several murine cancer models, now represents a promising therapeutic target in RCC. However, the potential expression of B7-H1 in metastatic RCC has not been investigated. In the current study, the authors updated their primary RCC results with additional follow-up and investigated the potential role of B7-H1 in metastatic RCC.
Methods: Between 2000 and 2004, 196 patients underwent nephrectomy and 26 patients had resection of RCC metastases for clear cell RCC. Immunohistochemical analysis was performed on tumor cryosections using a B7-H1 monoclonal antibody (clone 5H1). A urologic pathologist quantified the percentage of B7-H1-positive tumor cells and lymphocytes.
Results: Variable levels of B7-H1 were expressed on primary RCC tumor cells (n = 130 [66.3%]) and primary tumor-infiltrating lymphocytes (n = 115 [58.7%]). Patients with high expression of B7-H1 on primary tumor cells and/or lymphocytes were significantly more likely to die of RCC compared with patients with low B7-H1 expression (risk ratio [RR] = 4.17; 95% confidence interval [95% CI], 1.97-8.84; P < 0.001) and this risk persisted in multivariate analysis after adjusting for the Mayo Clinic stage, size, grade, and necrosis score (RR = 2.63; 96% CI, 1.23-5.64; P = 0.013). Of the 26 metastatic specimens, cancer cell and lymphocyte B7-H1 expression were demonstrated in 17 (65.4%) and 18 (69.2%) specimens, respectively. In total, 14 (54.3%) metastatic specimens had high aggregate B7-H1 levels compared with 44.4% in primary RCC specimens.
Conclusions: Patients with RCC with high B7-H1 expression were significantly more likely to die even after multivariate analysis. The authors also demonstrated that a high percentage of RCC metastases similarly harbored B7-H1. The authors surmised that B7-H1 blockade may augment current immunotherapy, including patients treated for metastases after cytoreductive nephrectomy.
Copyright 2005 American Cancer Society
Source: PubMed