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Expression of X-Linked Inhibitor of Apoptosis Protein Is a Strong Predictor of Human Prostate Cancer Recurrence

Authors' Affiliations: Departments of ¹ Pathology and Laboratory Medicine, ² Biostatistics, ³ Human Genetics, ⁴ Microbiology, Immunology and Molecular Genetics, ⁵ Jonsson Comprehensive Cancer Center David Geffen School of Medicine at the University of California at Los Angeles, Los Angeles, California; ⁶ Department of Urology, Kyoto Second Red Hospital, ⁷ Department of Urology, Kyoto Prefectural University of Medicine, Kyoto, Japan; and ⁸ Unidad de Investigacion en Enfermedades Oncologicas, Hospital Infantil de Mexico, Federico Gomez Mexico D.F. Mexico

Requests for reprints: Lee Goodglick, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Ave, Box 951747, 1P-430 CHS, Los Angeles, CA 90095-1747. Phone: 310-825-9134; E-mail: lgoodglick{at}mednet.ucla.edu.

Purpose: 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.

Experimental Design: 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.