Survivin and B7-H1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma

Amy E. Krambeck, Haidong Dong, R. Houston Thompson, Susan M. Kuntz, Christine M. Lohse, Bradley C. Leibovich, Michael L. Blute, Thomas J. Sebo, John C. Cheville, Alexander S. Parker, Eugene D. Kwon

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81 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1749-1756
Number of pages8
JournalClinical Cancer Research
Volume13
Issue number6
DOIs
StatePublished - Mar 15 2007

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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