Immunohistochemical demonstration of phospho-Akt in high gleason grade prostate cancer

Shazli N. Malik, Michael Brattain, Paramita M. Ghosh, Dean A. Troyer, Thomas Prihoda, Roble Bedolla, Jeffrey I. Kreisberg

Research output: Contribution to journalArticle

285 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1168-1171
Number of pages4
JournalClinical Cancer Research
Volume8
Issue number4
StatePublished - Apr 1 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Malik, S. N., Brattain, M., Ghosh, P. M., Troyer, D. A., Prihoda, T., Bedolla, R., & Kreisberg, J. I. (2002). Immunohistochemical demonstration of phospho-Akt in high gleason grade prostate cancer. Clinical Cancer Research, 8(4), 1168-1171.