Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer.
OBJECTIVE
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.


METHODS
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 < or = 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).


CONCLUSIONS
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.
Malik
Shazli N
SN
Department of Surgery, University of Texas Health Science Center, San Antonio, Texas 78229, USA.
Brattain
Michael
M
Ghosh
Paramita M
PM
Troyer
Dean A
DA
Prihoda
Thomas
T
Bedolla
Roble
R
Kreisberg
Jeffrey I
JI
D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010768:Phosphoserine / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt
D011518:Proto-Oncogene Proteins; D010768:Phosphoserine; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases