title: Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer.
abstract: 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.
authors.affiliation: Department of Surgery, University of Texas Health Science Center, San Antonio, Texas 78229, USA.
authors.forename: Shazli N
authors.initials: SN
authors.lastname: Malik
authors.forename: Michael
authors.initials: M
authors.lastname: Brattain
authors.forename: Paramita M
authors.initials: PM
authors.lastname: Ghosh
authors.forename: Dean A
authors.initials: DA
authors.lastname: Troyer
authors.forename: Thomas
authors.initials: T
authors.lastname: Prihoda
authors.forename: Roble
authors.initials: R
authors.lastname: Bedolla
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Kreisberg
mesh_terms: 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
chemical_list: 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