[733] Increased Phosphorylated 4EBP1 Expression in Minute Prostatic Adnocarcinoma.

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

Background: Phosphorylation of 4EBP1 results in the release of eukaryotic initiation factor 4E and increased cap-dependent translation of a set of proteins involved in G₁-S-phase. Reduced phosphorylated 4EBP1 expression was significantly associated with dramatically shortened survival in prostatic cancer. We aimed to evaluate phosphorylated 4EBP1 expression in minimal (insignificant) prostate adenocarcinoma (MinPCa), defined as tumors with insufficient virulence to threaten survival.
Design: Tissue microarrays were constructed from 33 consecutive radical prostatectomy spemcimens containing MinPCa. Each tumor and paired benign tissue was represented by up to triplicate,1mm, spots. Standard immunohistochemistry analysis for phosphorylated 4EBP1 was performed. Staining pattern was evaluated as nuclear vs. cytoplasmic, Percentage of positive cells (extent) and intensity (0 to 3+) of staining was assigned in each spot. A final H-score (product of intensity x extent) was calculated per spot and averaged among spots representing a single sample.
Results: Cytoplasmic and nuclear p4EBP1 expression (H scores) were significantly higher in MinPCa cancer tissues compared to benign tissues (p=0.0001 and p=0.0003 respectively). Only a minorty of MinPCa tumors (4/34; 11%) revealed cytoplasmic p4EBP1 levels lower than the mean level of their paired benign glands (Hscore <25).

p4EBP1 Hscore in benign prostatic tissue vs. adenocarcinoma

	No cases	Cytoplasmic p4EBP1 Hscore mean (range)	nuclear p4EBP1 Hscore mean	p value
Benign prostatic tissue	34	25 (0-100)	96 (10-230)	0.0001
Adenocarcinoma	34	136 (0-300)	162 (0-300)	0.0003

Conclusions: We found significantly increased cytoplamic and nuclear expression of phosphorylated 4EBP1 in our cohort of MinPCa compared to paired non neoplastic prostate tissue. Our finding of decreased phosphorylated 4EBP1 levels only in a minority of tumors in this cohort of clinically insignificant minimal prostate carcinoma is in line with the previously suggested aggressive prognostic implication for marked reduction in phosphorylated 4EBP1 expression.
Category: Genitourinary (including renal tumors)

Monday, February 28, 2011 1:00 PM

Poster Session II # 147, Monday Afternoon