High levels of phosphorylated form of Akt-1 in prostate cancer and non-neoplastic prostate tissues are strong predictors of biochemical recurrence Journal Article
| Authors: | Ayala, G.; Thompson, T.; Yang, G.; Frolov, A.; Li, R.; Scardino, P.; Ohori, M.; Wheeler, T.; Harper, W. |
| Article Title: | High levels of phosphorylated form of Akt-1 in prostate cancer and non-neoplastic prostate tissues are strong predictors of biochemical recurrence |
| Abstract: | 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 Gleasoa 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. |
| Keywords: | immunohistochemistry; protein kinase b; adult; cancer survival; controlled study; human tissue; protein expression; protein phosphorylation; aged; aged, 80 and over; disease-free survival; middle aged; retrospective studies; unclassified drug; major clinical study; proto-oncogene proteins; cancer recurrence; follow up; follow-up studies; cohort studies; neoplasm recurrence, local; phosphorylation; prediction; prostate cancer; prostatic neoplasms; prostate; correlation analysis; probability; protein-serine-threonine kinases; disease progression; prostate tumor; proto-oncogene proteins c-akt; predictive value of tests; cytoplasm; multivariate analysis; cancer tissue; biochemistry; biochemical marker; protein content; protein akt1; humans; prognosis; human; male; priority journal; article |
| Journal Title: | Clinical Cancer Research |
| Volume: | 10 |
| Issue: | 19 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2004-10-01 |
| Start Page: | 6572 |
| End Page: | 6578 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-04-0477 |
| PROVIDER: | scopus |
| PUBMED: | 15475446 |
| DOI/URL: | |
| Notes: | Clin. Cancer Res. -- Cited By (since 1996):118 -- Export Date: 16 June 2014 -- CODEN: CCREF -- Source: Scopus |
