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).
|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|