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BackgroundExpanding interest in and use of active surveillance for early state prostate cancer (PC) has increased need for prognostic biomarkers. Using a multi-institutional tissue microarray resource including over 1000 radical prostatectomy samples, we sought to correlate Ki67 expression captured by an automated image analysis system with clinicopathological features and validate its utility as a clinical grade test in predicting cancer-specific outcomes.MethodsAfter immunostaining, the Ki67 proliferation index (PI) of tumor areas of each core (three cancer cores/case) was analyzed using a nuclear quantification algorithm (Aperio). We assessed whether Ki67 PI was associated with clinicopathological factors and recurrence-free survival (RFS) including biochemical recurrence, metastasis or PC death (7-year median follow-up).ResultsIn 1004 PCs (∼4000 tissue cores) Ki67 PI showed significantly higher inter-tumor (0.68) than intra-tumor variation (0.39). Ki67 PI was associated with stage (P

In this study, we have taken advantage of over-expression of eukaryotic translation initiation factor 4E (eIF4E) in prostate cancer cells to design a viral-based targeting system of prostate cancer. Three different lengths of 5′-untranslated regions (5′UTRs) derived from either fibroblast growth factor-2 (FU-FGF2-GW) or ornithine decarboxylase (FU-ODC149-GW and FU-ODC274-GW) were inserted upstream of enhanced green fluorescent protein (GFP) gene in a lentiviral backbone. Both nonmalignant control (PNT1B and BPH-1) and neoplastic (LNCaP, C4-2, DU145 and PC-3) prostate cell lines were transfected with each plasmid or virus alone, or in the presence of siRNA against eIF4E, and their expression was monitored via GFP protein levels. Two 5′UTRs (FU-FGF2-GW and FU-ODC-GW) were selected as being most sensitive to eIF4E status. Lentiviruses containing these sequences were injected directly into the prostates of PTEN−/− (tumor-bearing) and control mice. Immunofluorescence data and western blot analyses determined that a lentivirus containing a 5′UTR derived from FGF-2 is the best candidate for directing selective gene expression in the prostate tumors of PTEN−/− mice in vivo. This study demonstrates that judicious selection of a complex 5′UTR can enhance selective targeting of viral-based gene therapies for prostate cancer. [ABSTRACT FROM AUTHOR]