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Akt is a serine-threonine-kinase that phosphorylates proteins in several pathways regulating aspects of metabolism, apoptosis,
and proliferation. Akt signaling promotes proliferation and increased cell survival and is thought to play an important role
in prostate cancer progression. Tissue microarrays (640 patients) with triplicate cores of non-neoplastic prostate, BPH, and
index tumor were immunostained with antibody to Phospho-Akt (Ser473), digitized, and quantified. The expression index (Intensity*Percentage)
was used for statistical analysis. P-Akt-1 staining was found in both the non-neoplastic and cancer tissues, predominantly
in cytoplasmic locations. High level P-Akt-1 is expressed almost exclusively in cancer. By Kaplan-Meier actuarial model, high
expression of P-Akt-1 in prostate cancer was predictive of a higher probability of recurrence on univariate and multivariate
analysis. Akt-1 expression was an independent prognostic indicator of biochemical recurrence-free survival when Gleason 6
and 7 patients were analyzed separately. Surprisingly, a high level of P-Akt-1 expression in non-neoplastic tissues is also
an independent predictor of biochemical recurrence. This suggests that some patients might have an inherent predisposition
to express a high level of P-Akt-1 and, therefore, to have an adverse prognosis. We conclude that P-Akt-1 is most likely involved
in the progression of prostate cancer and is an excellent biomarker for biochemical recurrence.