Expression of X-linked inhibitor of apoptosis protein is a strong predictor of human prostate cancer recurrence.
OBJECTIVE
The X-linked inhibitor of apoptosis protein (XIAP) is associated with cell survival by blocking caspase-mediated apoptosis. We examined the expression patterns of XIAP with regard to human prostate cancer, predicting that XIAP status may predict cancer recurrence and/or clinical outcome.


METHODS
Immunohistochemistry was done on tissue microarrays constructed from 226 primary prostate cancer specimen. The protein expression distribution was examined across the spectrum of epithelial tissues and its association with standard clinicopathologic covariates and tumor recurrence was examined in 192 outcome-informative patients.


RESULTS
The mean XIAP expression was significantly higher in prostate cancer compared with prostatic intraepithelial neoplasia (PIN), normal, and benign prostatic hyperplasia. We observed that XIAP is an independent predictor of tumor recurrence in multivariate Cox proportional hazards analysis in all patients as well as after substratifying by Gleason score. Interestingly, patients with high XIAP levels had a much lower probability of tumor recurrence than those with lower XIAP expression. Even patients with high-grade tumors who had higher XIAP levels had a lower risk of recurrence compared with any patient whose tumors express lower XIAP.


CONCLUSIONS
XIAP is expressed at higher levels in prostate cancers compared with matched normal tissues. High XIAP expression is strongly associated with a reduced risk of tumor recurrence and is not directly associated with Gleason score, tumor stage, capsular involvement, or preoperative prostate-specific antigen status, suggesting that it is a novel prognosticator and a potential target for prostate cancer diagnosis and therapy. Significantly, these findings provide important and extensive validation of previous results.
Seligson
David B
DB
Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California 90095-1747, USA.
Hongo
Fumiya
F
Huerta-Yepez
Sara
S
Mizutani
Yoichi
Y
Miki
Tsuneharu
T
Yu
Hong
H
Horvath
Steve
S
Chia
David
D
Goodglick
Lee
L
Bonavida
Benjamin
B
D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D000368:Aged; D015331:Cohort Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D012008:Recurrence; D016896:Treatment Outcome; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000096:biosynthesis*
D051636:X-Linked Inhibitor of Apoptosis Protein; D017430:Prostate-Specific Antigen