Prognostic Value of Bone Sialoprotein Expression in Clinically Localized Human Prostate Cancer

• Published in: JNCI : Journal of the National Cancer Institute Vol. 90; no. 13; pp. 1000 - 1008
• Main Authors: Waltregny, David, Bellahcène, Akeila, Castronovo, Vincent, Dewé, Walthère, de Leval, Jean, Van Riet, Ivan, Fisher, Larry W., Young, Marian, Fernandez, Pedro
• Format: Journal Article Web Resource
• Language: English
• Published: Cary, NC Oxford University Press 01.07.1998; Oxford Publishing Limited (England)
• Subjects: Adenocarcinoma - chemistry; Aged; Biological and medical sciences; Bone and Bones - chemistry; Bones; Disease-Free Survival; Gene Expression Regulation, Neoplastic; Human health sciences; Humans; Immunoenzyme Techniques; In Situ Hybridization; Integrin-Binding Sialoprotein; Male; Medical research; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prostate cancer; Prostatic Neoplasms - chemistry; Proteins; RNA, Messenger - analysis; RNA, Neoplasm - analysis; Sciences de la santé humaine; Sialoglycoproteins - analysis; Sialoglycoproteins - genetics; Tumors of the urinary system; Urinary tract. Prostate gland; Urologie & néphrologie; Urology & nephrology; Human; Immunohistochemistry; Urinary system disease; Prostate disease; In situ; Male; Hybridization; Metastasis; Malignant tumor; Protein; Immunoperoxidase technique; Pathology; Clinical stage; Sialoproteins; Extracellular matrix; Diagnosis; Bone; Molecular biology; Male genital diseases; Prostate; Localized
• ISSN: 0027-8874; 1460-2105; 1460-2105
• DOI: 10.1093/jnci/90.13.1000

Background: Bone sialoprotein (BSP), a bone matrix protein, was recently found to be expressed ectopically in breast cancer and to have a statistically significant association with poor prognosis and the development of bone metastases in that disease. These data prompted us to investigate 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 radical prostatectomy for localized prostate cancer were analyzed immunohistochemically for BSP expression. Biochemical progression was defined 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 proportional hazards model was used to determine which clinical and histologic parameters, including stage, Gleason score, and BSP expression (immunostaining intensity and extent), were independently associated with biochemical progression. All P values were two-sided. Results: Most of the prostate cancer lesions examined (78.9%) expressed detectable levels of BSP, compared with no or low expression in the adjacent normal glandular tissue. A statistically significant association was found between BSP expression and biochemical progression in both univariate and multivariate analyses After a follow-up interval of 3 years, the biochemical relapse rate was 36.7% (95% confidence interval [CI] = 23.4%47.7%) in patients whose tumors expressed high levels of BSP compared with 12.1% (95% C1 = 2.3%–20.8%) in patients whose tumors expressed no or a low detectable level of the protein (logrank test, P = .0014). BSP expression status could identify those patients at higher risk of biochemical progression (logrank test, P:lt;.05) among patients with moderately differentiated tumors or with pathologically confined tumors. Conclusions: To our knowledge, this study is 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. [J Nall Cancer Inst 1998;90:1000–8]