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Osteopontin and Interleukin-8 Expression is Independently Associated with Prostate Cancer Recurrence

Authors' Affiliations: Departments of ¹ Urology, ² Cell Biology and Anatomy, ³ Sylvester Comprehensive Cancer Center, ⁴ Epidemiology and Public Health, and ⁵ Radiation Oncology, Miller School of Medicine, University of Miami, Florida

Requests for reprints: Bal L. Lokeshwar, Department of Urology (M-800), P.O. Box 016960 Miami, FL 33101. Phone: 305-243-1012; Fax: 305-243-6893; E-mail: blokeshw{at}med.miami.edu.

Purpose: Lack of reliable biomarkers limits accurate prediction of prostate-specific antigen biochemical recurrence (disease progression) in prostate cancer. The two inflammatory chemokines, osteopontin and interleukin-8 (IL-8), are associated with tumor angiogenesis and metastasis. We investigated whether osteopontin and IL-8 expression in prostate cancer correlates with disease progression.

Experimental Design: Archival prostatectomy specimens (n = 103) were obtained from patients with minimum 72-month follow-up. Osteopontin and IL-8 expression was evaluated by immunohistochemistry and graded for intensity and the area. Association of osteopontin and IL-8 staining with biochemical recurrence was evaluated by univariate and multivariate models.

Results: In tumor cells, osteopontin and IL-8 staining was higher in the recurred group (203.2 ± 78.4; 181.1 ± 89.3) than in the nonrecurred group (122.7 ± 76.6; 96.4 ± 85.6; P < 0.001). Higher osteopontin and IL-8 staining was also observed in benign areas adjacent to tumor in the recurred group, than in nonrecurred group. In univariate analysis, except age, all preoperative and postoperative variables and osteopontin and IL-8 staining scores were significantly associated with biochemical recurrence (P < 0.05). In multivariate analysis, margin status and osteopontin staining independently associated with biochemical recurrence within 72 months. Osteopontin, either alone or with IL-8 and seminal vesicle invasion, was a significant variable in predicting biochemical recurrence within 24 months. Osteopontin and IL-8 staining predicted recurrence with high sensitivity (75.5%; 73.6%) and specificity (76%; 70.6%).

Conclusion: In prostatectomy specimens, osteopontin expression is independently associated with biochemical recurrence. Both osteopontin and IL-8 may be predictors of early disease progression.