High levels of phosphorylated form of Akt-1 in prostate cancer and non-neoplastic prostate tissues are strong predictors of biochemical recurrence.
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.
Ayala
Gustavo
G
Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA. gayala@bcm.tmc.edu
Thompson
Timothy
T
Yang
Guang
G
Frolov
Anna
A
Li
Rile
R
Scardino
Peter
P
Ohori
Makoto
M
Wheeler
Thomas
T
Harper
Wade
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011379:Prognosis; D011467:Prostate / Q000737:chemistry / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D012189:Retrospective Studies
D011518:Proto-Oncogene Proteins; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt