Immunohistochemical Demonstration of Phospho-Akt in High Gleason Grade Prostate Cancer

• Published in: Clinical cancer research Vol. 8; no. 4; pp. 1168 - 1171
• Main Authors: MALIK, Shazli N, BRATTAIN, Michael, GHOSH, Paramita M, TROYER, Dean A, PRIHODA, Thomas, BEDOLLA, Roble, KREISBERG, Jeffrey I
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.04.2002
• Subjects: Biological and medical sciences; Humans; Immunohistochemistry; Male; Medical sciences; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases - metabolism; Nephrology. Urinary tract diseases; Phosphoserine - metabolism; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Tumors of the urinary system; Urinary tract. Prostate gland; Histological grading; Human; Urinary system disease; Prostate disease; Enzyme; Gene product; Transferases; Tumoral tissue; Malignant tumor; Gene expression; Carcinogenesis; In vitro; Signal transduction; Cell death; Protein kinase; Tumor progression; Male genital diseases; Prostate; High malignancy
• ISSN: 1078-0432; 1557-3265

Purpose: Whereas the early stage of prostate cancer is marked by excessive proliferation, in advanced stages of the disease, a decreased apoptotic death rate (increased cell survival) also contributes to net tumor growth. Altered regulation of the mitogen-activated protein kinase (MAPK)-regulated cell proliferation and Akt-regulated cell survival pathways are suspected causes. In this study, we wanted to determine: ( a ) whether the degree of Akt activation can be assessed by immunohistochemical staining of paraffin- embedded human prostate cancer biopsies with an antibody to phospho-Akt (Ser473); and ( b ) whether phospho-MAPK/Erk1/2 and phospho-Akt expression are altered in prostate cancer. Experimental design: To examine the activation status of MAPK/Erk1/2 and Akt, archival paraffin-embedded sections from 74 cases of resected prostate cancer were immunostained with antibodies to phospho-MAPK/Erk1/2 (Thr202/ Tyr204) and phospho-Akt (Ser473). Results: The staining intensity for phospho-Akt was significantly greater in Gleason grades 8–10 (92% of such cases staining strongly) compared with prostatic intraepithelial neoplasia and all other grades of prostate cancer (only 10% of these cases staining strongly; P ≤ 0.001). The staining intensity for phospho-MAPK/Erk, on the other hand, was significantly greater for normal, hyperplastic, and prostatic intraepithelial neoplasia lesions but declined with disease progression, reaching its lowest level of expression in high Gleason grades 8–10 ( P < 0.0001). Conclusion: The activation state of the cell survival protein Akt can be analyzed in human prostate cancer by immunohistochemical staining of paraffin-embedded tissue with a phospho-specific Akt (Ser473) antibody. Advanced disease is accompanied by activation of Akt and inactivation of Erk.