[839] Immunohistochemical Expression of Secretory Clusterin (sCLU) in Benign and Malignant Prostate in the Context of Hormonal Therapy

L Fahim, N Cockburn, A Joshua, P Warde, J Sweet. University Health Network, Toronto, Canada

Background: Clusterin (apolipoprotein J) is an androgen-repressed oncogenic molecule involved in cell cycle regulation, cell survival and DNA repair. In prostate cancer (PCa), secretory Clusterin (sCLU) is linked to androgen resistance and post therapy cell survival. Anti-sense oligonuleotide repression of CLU gene has been shown to inhibit prostate cancer progression in phase-1 clinical trials. We investigated the immunohistochemical (IHC) expression of sCLU in benign prostate epithelium, surgically treated PCa with no prior therapy (SRx), hormone responsive PCa (HRsv) and hormone resistant PCa (HR).
Design: Prostate tissue from 10 cystoprostatectomies with no cancer, 25 (HR) cases from TURPS, 24 (HRsv) cases from radical prostatectomies (RP) and 72 SRx cases including, 35 Gleason score (GS) 6 and 37 high grade (HG) (GS 8,9,10) cases were used to construct 5 TMAs. Each case was represented by 3, 1mm cores. TMAs were stained with H&E and IHC was performed for sCLU. Epithelial expression of sCLU was scored as negative(0), weak(+1) or strong(+2) in each core. The summed scores from a case formed the composite score for that case and a mean score for each array was calculated.
Results: sCLU was not observed in benign prostate epithelium. sCLU was differentially expressed in SRx, HR and HRsv. sCLU was expressed in SRx PCa (GS 6 and HG) and a statistically significant increase in sCLU was observed in HG PCa compared to GS 6 PCa (p<0.0001). HRsv PCa showed significantly less expression of sCLU compared to HR PCa. HR PCa highly expressed sCLU at a level comparable to that of HG PC with no statitistical difference between these 2 groups.

IHC expression of sCLU in different study groups
study groupsNO of patientsmean score of sCLU staining in each group
Benign prostate100
Gleason 6351.1
HG373.7
HRsv242.0
HR253.72



Conclusions: sCLU expression was stronger in HG compared to GS 6, suggesting a positive correlation between sCLU and GS. Increased expression of sCLU may impart a cell survival advantage and may influence the aggressive nature of a specific PCa. Increased expression of sCLU in HR compared to HRsv may be linked to androgen resistance, implicating sCLU as a putative prosurvival factor. These findings are clinically relevant with respect to prognostication and the development of novel therapeutic strategies to inhibit sCLU.
Category: Genitourinary (including renal tumors)

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 121, Monday Morning

 

Close Window