PROGNOSTIC VALUE OF BONE SIALOPROTEIN EXPRESSION IN CLINICALLY LOCALIZED HUMAN PROSTATE-CANCER

Background- Bone sialoprotein (BSP), a bone matrix protein, was recent ly found to be expressed ectopically in breast cancer and to have a st atistically significant association with poor prognosis and the develo pment of bone metastases in that disease. These data prompted us to in vestigate whether BSP might also be expressed in human prostate cancer , which often metastasizes to bone, and be predictive for progression risk, Methods: Tissue sections from 180 patients who had undergone a r adical prostatecomy for localized prostate cancer were analyzed immuno histochemically for BSP expression, Biochemical progression was define d as an increasing serum prostate-specific antigen level of 0.5 ng/mL or more. Statistical analysis was used to assess associations between pathologic findings and level of BSP expression, and a Cox proportiona l hazards model was used to determine which clinical and histologic pa rameters, including stage, Gleason score, and BSP expression (immunost aining intensity and extent), were independently associated with bioch emical progression, All Pvalues were two-sided. Results: Most of the p rostate cancer lesions examined (75.9%) expressed detectable levels of BSP, instability in epithelial borderline pared with no or low expres sion in the adjacent normal glandular tissue. A statistically sufficie nt association was found between BSP expression and biochemical progre ssion in both univariate and multivariate analyses. After a follow-up interval of 3 years, the biochemical relapse rate was 36.7% (95% confi dence interval [CI] = 23.4%-47.7%) in patients whose tumors expressed high levels of BSP compared with 12.1% (95% CI = 2.3%-20.8%) in patien ts whose tumors expressed no or a low detectable level of the protein (log-rank test, P =,0014). BSP expression status could identify those patients at higher risk of biochemical progression (log-rank test, P<. 05) among patients with moderately differentiated tumors or with patho logically confined tumors. Conclusions: To our knowledge, this study i s the first to demonstrate BSP expression in human prostate cancer and to highlight the protein's statistically significant prognostic value in patients with clinically confined prostate adenocarcinomas.