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

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

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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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Renal Cell Carcinoma
Survival
Neoplasms
Therapeutics
Cell Death
Odds Ratio
Confidence Intervals
T-Lymphocytes
Nephrectomy
Proportional Hazards Models
Disease Progression
Immune System
Research Design
Multivariate Analysis
Survival Rate

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Survivin and B7-H1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma. / Krambeck, Amy E.; Dong, Haidong M; Thompson, R. Houston; Kuntz, Susan M.; Lohse, Christine M.; Leibovich, Bradley C.; Blute, Michael L.; Sebo, Thomas J.; Cheville, John C.; Parker, Alexander; Kwon, Eugene D.

In: Clinical Cancer Research, Vol. 13, No. 6, 15.03.2007, p. 1749-1756.

Research output: Contribution to journalArticle

Krambeck, Amy E. ; Dong, Haidong M ; Thompson, R. Houston ; Kuntz, Susan M. ; Lohse, Christine M. ; Leibovich, Bradley C. ; Blute, Michael L. ; Sebo, Thomas J. ; Cheville, John C. ; Parker, Alexander ; Kwon, Eugene D. / Survivin and B7-H1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 6. pp. 1749-1756.
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title = "Survivin and B7-H1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma",
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.",
author = "Krambeck, {Amy E.} and Dong, {Haidong M} and Thompson, {R. Houston} and Kuntz, {Susan M.} and Lohse, {Christine M.} and Leibovich, {Bradley C.} and Blute, {Michael L.} and Sebo, {Thomas J.} and Cheville, {John C.} and Alexander Parker and Kwon, {Eugene D}",
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T1 - Survivin and B7-H1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma

AU - Krambeck, Amy E.

AU - Dong, Haidong M

AU - Thompson, R. Houston

AU - Kuntz, Susan M.

AU - Lohse, Christine M.

AU - Leibovich, Bradley C.

AU - Blute, Michael L.

AU - Sebo, Thomas J.

AU - Cheville, John C.

AU - Parker, Alexander

AU - Kwon, Eugene D

PY - 2007/3/15

Y1 - 2007/3/15

N2 - 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.

AB - 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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