Increase of AKT/PKB expression correlates with Gleason pattern in human prostate cancer

AKT/PKB is a central signaling molecule related to stimulation of cell proliferation and inhibition of apoptosis. Perturbations of AKT expression and function play an important role in tumor development and progression. We wanted to determine (a) whether AKT is overexpressed in human prostatic tumors, (b) whether AKT expression is correlated with tumor grade, and (c) whether AKT expression correlates with clinicopathological parameters. AKT expression was investigated by immunohistochemistry in sections from S6 paraffin-embedded prostate specimens displaying benign prostatic tissue (BPT), prostatic intraepithelial neoplasia (PIN), and primary tumors graded 2-5 according to Gleason. The staining intensity for AKT was significantly more pronounced in tumors compared to BPT, with PIN ranging between BPT and carcinomas. Similarly, the fraction of AKT-positive cells was higher in tumors than in BPT. A score of AKT expression (calculated as product from intensity and fraction of positive cells) ranging from 0-6 was also significantly higher in tumors than in BPT. Furthermore, the intensity of AKT expression in tumors showed a positive correlation with high preoperative serum levels of prostate specific antigen (PSA greater than or equal to 10 ng/ml, p = 0.0325). These data show that AKT is upregulated in prostate cancer and that expression is correlated with tumor progression. (C) 2003 Wiley-Liss, Inc.