Prognostic value of survivin in locally advanced prostate cancer: study based on RTOG 8610.
OBJECTIVE
To examine the prognostic value of nuclear and cytoplasmic survivin expression in men with locally advanced prostate cancer who were enrolled in Radiation Therapy Oncology Group (RTOG) protocol 8610.


METHODS
RTOG 8610 was a Phase III randomized study comparing the effect of radiotherapy plus short-term androgen deprivation with radiotherapy alone. Of the 456 eligible patients, 68 patients had suitably stained tumor material for nuclear survivin analysis and 65 patients for cytoplasmic survivin.


RESULTS
Compared with patients with nuclear survivin intensity scores of <or=191.2, those with intensity scores >191.2 had significantly improved prostate cancer survival (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.20-1.00, p = 0.0452). On multivariate analysis, nuclear survivin intensity scores >191.2 were significantly associated with improved overall survival (HR, 0.46; 95% CI, 0.25-0.86; p = 0.0156) and prostate cancer survival (HR, 0.36; 95% CI, 0.16-0.84; p = 0.0173). On univariate analysis, compared with patients with cytoplasmic survivin integrated optical density <or=82.7, those with an integrated optical density >82.7 showed a significantly increased risk of local progression (HR, 2.49; 95% CI, 1.03-6.01; p = 0.0421).


CONCLUSIONS
Nuclear overexpression of survivin was associated with improved overall and prostate cancer survival on multivariate analysis, and cytoplasmic overexpression of survivin was associated with increased rate of local progression on univariate analysis in patients with locally advanced prostate cancer treated on RTOG 8610. Our results might reflect the different functions of survivin and its splice variants, which are known to exist in distinct subcellular compartments.
Zhang
Min
M
Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Ho
Alex
A
Hammond
Elizabeth H
EH
Suzuki
Yoshiyuki
Y
Bermudez
R Scott
RS
Lee
R Jeffrey
RJ
Pilepich
Michael
M
Shipley
William U
WU
Sandler
Howard
H
Khor
Li-Yan
LY
Pollack
Alan
A
Chakravarti
Arnab
A
D000368:Aged; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000627:therapeutic use; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D002467:Cell Nucleus / Q000737:chemistry; D017326:Clinical Trials, Phase III as Topic; D003593:Cytoplasm / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D000077022:Survivin
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin