title: Survivin and b7-h1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology, Mayo Medical School, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Krambeck
authors.forename: Haidong
authors.initials: H
authors.lastname: Dong
authors.forename: R Houston
authors.initials: RH
authors.lastname: Thompson
authors.forename: Susan M
authors.initials: SM
authors.lastname: Kuntz
authors.forename: Christine M
authors.initials: CM
authors.lastname: Lohse
authors.forename: Bradley C
authors.initials: BC
authors.lastname: Leibovich
authors.forename: Michael L
authors.initials: ML
authors.lastname: Blute
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Sebo
authors.forename: John C
authors.initials: JC
authors.lastname: Cheville
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Parker
authors.forename: Eugene D
authors.initials: ED
authors.lastname: Kwon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism / Q000502:physiology*; D060890:B7-H1 Antigen; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism / Q000502:physiology*; D011379:Prognosis; D000077022:Survivin
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; C107489:BIRC5 protein, human; C423236:CD274 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin