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Survivin and B7-H1 Are Collaborative Predictors of Survival and Represent Potential Therapeutic Targets for Patients with Renal Cell Carcinoma

Authors' Affiliations: Departments of ¹ Urology, ² Immunology, ³ Health Sciences Research, and ⁴ Laboratory Medicine and Pathology, Mayo Medical School, Mayo Clinic, Rochester, Minnesota and ⁵ Department of Urology, Mayo Clinic, Jacksonville, Florida

Requests for reprints: Eugene D. Kwon, Departments of Urology and Immunology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Phone: 507-284-8371; Fax: 507-284-4987; E-mail: kwon.eugene{at}mayo.edu.

Purpose: Clear cell renal cell carcinoma (ccRCC) is an immunogenic tumor that can progress in the presence of an intact host immune system. We previously reported that survivin and B7-H1 are independently associated with disease progression and death when expressed by ccRCC tumors. Herein, we examine the clinical effect of ccRCC combined expression of both survivin and B7-H1.

Experimental Design: Specimens from 298 patients who underwent nephrectomy for ccRCC between 1990 and 1994 were immunohistochemically stained for survivin and B7-H1. Cancer-specific survival was estimated using the Kaplan-Meier method. Associations of both markers with ccRCC death were assessed using Cox proportional hazards regression models.

Results: At last follow-up, 94 patients died from ccRCC. Among the living patients, the median follow-up was 11.2 years (range, 0-15 years). There were 177 (59.4%) survivin^Low/B7-H1^–, 51 (17.1%) survivin^Hi/B7-H1^–, 29 (9.7%) survivin^Low/B7-H1⁺, and 41 (13.8%) survivin^Hi/B7-H1⁺ tumors. The 5-year cancer-specific survival rates for patients within each group were 89.3%, 59.7%, 70.0%, and 16.2%, respectively. Combined survivin^Hi/B7-H1⁺ expression was associated with ccRCC death univariately (risk ratio, 12.82; 95% confidence interval, 7.50-21.92; P < 0.001) and in multivariate analysis (risk ratio, 2.81; 95% confidence interval, 1.56-5.04; P < 0.001). Survivin^Hi/B7-H1⁺ tumors exhibited increased levels of infiltrating mononuclear cells and survivin-specific T cells compared with survivin^Low/B7-H1^– tumors.

Conclusion: Patients with survivin^Hi/B7-H1⁺ ccRCC tumors are at increased risk of ccRCC death. Survivin^Hi/B7-H1⁺ tumors also harbor increased amounts of infiltrating mononuclear cells and survivin-specific T cells relative to survivin^Low/B7-H1^– tumors. Taken together, dual expression of survivin and B7-H1 can be used to predict ccRCC tumor aggressiveness.

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				M. H. Andersen, I. M. Svane, J. C. Becker, and P. t. Straten The Universal Character of the Tumor-Associated Antigen Survivin Clin. Cancer Res., October 15, 2007; 13(20): 5991 - 5994. [Abstract] [Full Text] [PDF]