Survivin and b7-h1 are collaborative predictors of survival and represent potential therapeutic targets for patients with renal cell carcinoma.
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.
Krambeck
Amy E
AE
Department of Urology, Mayo Medical School, Mayo Clinic, Rochester, MN 55905, USA.
Dong
Haidong
H
Thompson
R Houston
RH
Kuntz
Susan M
SM
Lohse
Christine M
CM
Leibovich
Bradley C
BC
Blute
Michael L
ML
Sebo
Thomas J
TJ
Cheville
John C
JC
Parker
Alexander S
AS
Kwon
Eugene D
ED
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
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