Elevated Secreted Protein, Acidic, and Rich in Cysteine (SPARC) Expression in Prostate Cancer Correlates with Tumor Metastasis after Radical Prostatectomy
B Furusato, C DeRosa, Y Chen, L Ravindranath, C Cook, J Cullen, DG McLoed, G Petrovics, S Srivastava, IA Sesterhenn. Center for Prostate Disease Research, Rockville; Walter Reed Army Medical Center, Washington, DC; Armed Forces Institute of Pathology, Washington, DC
Background: Comparative gene expression signatures of well differentiated and poorly differentiated prostate cancer (CaP) along with knowledge based gene analysis highlighted alterations of SPARC, and genes linked to it, in poorly differentiated CaP. Quantitative determination of SPARC gene expression levels in prostate tumor cells has been associated with an increased risk of PSA recurrence, with poorly differentiated carcinoma with overall Gleason score 8-9. We hypothesized that determination of SPARC protein expression levels in prostatectomy specimens by immunohistochemistry (IHC) may have the potential to predict aggressive clinical behavior in post prostatectomy patients.
Design: Fifty four prostatectomies matched by Gleason grade and pathologic stage were studied. Twenty seven patients with metastasis after the surgery were compared to 27 without metastasis. All specimens were processed as whole mounts and stained for SPARC by immunohisto-chemistry. The sections were incubated with anti-SPARC mouse monoclonal antibody (Zymed Laboratories, Inc., CA, USA) at a dilution of 1:160 for 1 hour, followed by 30 minutes in biotinylated horse antimouse (Vecto, Burlingham, CA) at a dilution of 1:400, and ABC (Vector, Burlingham, CA) Vector VIP was used as chromogen. SPARC expression was scored by % of tumor cells positive on a scale of 1-4, staining intensity on a score of 1-3, and a combination of both. These scores were correlated with clinical-pathologic features.
Results: Higher SPARC protein expression was significantly associated with metastases compared to non-metastasis group after the prostatectomy by using Fisher exact test (p=0.0076) and ROC (AUC=0.789). SPARC protein expression was able to predict the development of metastases.
Conclusions: High SPARC expression in CaP is associated with an increased risk of tumor metastasis in this patient cohort. Quantitative determination of SPARC protein expression levels in radical prostatectomy specimens may have prognostic utility and may help stratify and treat patients with locally advanced CaP.
Category: Genitourinary (including renal tumors)
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 121, Wednesday Afternoon