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.
|No. cases||No ERG Rearangement||ERG Rearangement||p value|
|PTEN loss||1||0 (0%)||1 (100%)||p=1|
|No PTEN loss||28||14 (50%)||14 (50%)|
|pS6 negative||20||13 (65%)||7 (35%)||p=0.014|
|pS6 positive||9||2 (22%)||7 (77%)|