[734] PTEN and Phosphorylated S6 Expression in Clinically insignificant Prostate Adenocarcinoma: Correlation with ERG Fusion Status.

Roula Albadine, Alcides Chaux, Jessica Hicks, Angleo De Marzo, George J Netto. Johns Hopkins Medical Institution, Baltimore

Background: Loss of PTEN leads to activation of mTOR pathway and has been linked to poor survival in patients with prostatic cancer (PCa). Phosphorylated S6 (pS6) expression is a potential predictive marker of response in mTOR targeted therapy. Minimal or insignificant prostatic adenocarcinoma (MinPCa) is defined as PCa with Gleason Score 6 and tumor volume < 0.5 CC. Studies assessing mTOR pathway status in MinPCa are lacking. The current study evaluates PTEN and pS6 expression in MinPCa in correlation with previously assessed ERG fusion status.
Design: Tissue microarrays (TMA) were constructed from 45 consecutive prostatectomies performed in our hospital (2002-2003) and diagnosed as MinPCa. Each tumor and paired benign tissue was represented by up to triplicate 1mm spots. Standard immunohistochemistry analysis for mTOR pathway members PTEN, pS6 was performed. H-score was generated for each marker as a product of intensity (0 to 3+) x percent of positive cells. FISH analysis was previously performed using break-apart probes for 5' and 3' regions of ERG.
Results: PTEN expression was retained in 28/29 (97%) evaluable MinPCa while pS6 positivity was present in 9/29 (31%). We found a significant correlation between pS6 expression and TMPRSS2-ERG fusion status (p<0.05) with 77% of pS6 positive tumors showing ERG fusion. Surprisingly, of 9 tumors demonstrating pS6 expression, 8 (89%) did not show associated loss of PTEN tumor suppressor gene suggesting an alternative mechanism controlling pS6 activation in MinPCa.

PTEN and pS6 expression vs. ERG rearrangement in minute protatic carcinoma
 No. casesNo ERG RearangementERG Rearangementp value
PTEN loss10 (0%)1 (100%)p=1
No PTEN loss2814 (50%)14 (50%) 
pS6 negative2013 (65%)7 (35%)p=0.014
pS6 positive92 (22%)7 (77%) 

Conclusions: In our cohort of MinPCa, loss of PTEN was only a rare event (1/29 tumors). Loss of PTEN was not associated with ERG fusion. The latter is in contrast to prior studies suggesting a collaborative role of PTEN loss and ERG fusion in early prostate cancer development. ERG rearrangement was associated with pS6 expression independent of PTEN loss. This finding suggests an alternative signaling mechanism controlling pS6 activation in MinPCa and call for further analysis.
Category: Genitourinary (including renal tumors)

Monday, February 28, 2011 1:00 PM

Poster Session II # 97, Monday Afternoon


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