High Levels of Phosphorylated Form of Akt-1 in Prostate Cancer and Non-Neoplastic Prostate Tissues Are Strong Predictors of Biochemical Recurrence

• Published in: Clinical cancer research Vol. 10; no. 19; pp. 6572 - 6578
• Main Authors: AYALA, Gustavo, THOMPSON, Timothy, GUANG YANG, FROLOV, Anna, LI, Rile, SCARDINO, Peter, OHORI, Makoto, WHEELER, Thomas, HARPER, Wade
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.10.2004
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; Cohort Studies; Disease Progression; Disease-Free Survival; Follow-Up Studies; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Pharmacology. Drug treatments; Phosphorylation; Predictive Value of Tests; Prognosis; Prostate - chemistry; Prostate - pathology; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Protein-Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Retrospective Studies; Tumors; Relapse; Urinary system disease; Protein kinase B; Prostate disease; Malignant tumor; Predictive factor; Male genital diseases; Prostate cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-0477

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.