High expression levels of survivin protein independently predict a poor outcome for patients who undergo surgery for clear cell renal cell carcinoma.
BACKGROUND
In a previous study of gene array data, the authors identified survivin as a candidate marker of aggressiveness in clear cell renal cell carcinoma (ccRCC). What remained in question was whether survivin expression at the protein level is an independent predictor of disease progression and cancer-specific survival.


METHODS
Between 1990 and 1994, 312 patients underwent nephrectomy for ccRCC at Mayo Clinic Rochester and had paraffin tissue available. The authors performed immunohistochemistry with antisurvivin antibody, quantitated the expression by using an image-analysis system, and analyzed the association of survivin expression with disease progression and cancer-specific survival.


RESULTS
Within the cohort, 97 patients (31.1%) had high levels of survivin expression. Patients who had high survivin expression levels were at significantly increased risk of death from RCC compared with patients who had low expression levels (risk ratio [RR], 5.3; 95% confidence interval [95% CI], 3.5-7.9). The 5-year cancer-specific survival rate was 43.0% for patients with high survivin expression and 87.2% for patients with low survivin expression. In multivariate analysis, survivin expression remained associated with death from RCC even after adjusting for the Eastern Cooperative Oncology Group performance status; 2002 Tumor, Lymph Node, Metastases (TNM) stage groupings and nuclear grade (RR, 2.4; 95%CI, 1.5-3.8); and the Mayo Clinic composite TNM stage groupings, tumor size, nuclear grade, and tumor necrosis (SSIGN) score (RR, 1.8; 95%CI, 1.1-2.9). Among 273 patients who had localized ccRCC, survivin expression was associated significantly with cancer progression (RR, 3.9; 95%CI, 2.4-6.2).


CONCLUSIONS
Survivin expression is an independent predictor of ccRCC progression and death from RCC. Thus, survivin has the potential to offer additional prognostic information and to provide a novel target for the development of new adjuvant therapies.
Parker
Alexander S
AS
Department of Urology, Mayo Clinic College of Medicine, Jacksonville, Florida, USA. parker.alexander@mayo.edu
Kosari
Farhad
F
Lohse
Christine M
CM
Houston Thompson
R
R
Kwon
Eugene D
ED
Murphy
Linda
L
Riehle
Darren L
DL
Blute
Michael L
ML
Leibovich
Bradley C
BC
Vasmatzis
George
G
Cheville
John C
JC
D000368:Aged; D002292:Carcinoma, Renal Cell / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D007680:Kidney Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis* / Q000096:biosynthesis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis; D009392:Nephrectomy; D011237:Predictive Value of Tests; D015996:Survival Rate; D000077022:Survivin; D016896:Treatment Outcome; D015854:Up-Regulation
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin