Expression and localisation of Akt-1, Akt-2 and Akt-3 correlate with clinical outcome of prostate cancer patients.
We investigated the correlation between the expression and localisation of Akt-1, Akt-2, Akt-3, phospho-Akt proteins and the clinicopathological parameters in 63 prostate cancer specimens. More than 60% of cancerous tissues overexpressed Akt-1, Akt-2 or Akt-3. Cytoplasmic Akt-1 expression was correlated with a higher risk of postoperative prostate-specific antigen (PSA) recurrence and shorter PSA recurrence interval. Cytoplasmic Akt-2 did not show any significant correlation with clinicopathological parameters predicting outcomes. Cytoplasmic Akt-3 was associated with hormone-refractory disease progression and extracapsular invasion. Nuclear Akt-1 and Akt-2 expression were correlated with favourable outcome parameters such as absence of lymph node and perineural invasion. Kaplan-Meier analysis and Cox regression model also showed that Akt-1 and Akt-2, but not Akt-3 or phospho-Akt was associated with a significantly higher risk of PSA recurrence. In contrast, nuclear Akt-1 was significantly associated with a lower risk of PSA recurrence. Multivariate analysis revealed that clinical stage, Gleason score and the combined cytoplasmic nuclear Akt-1 marker in cancerous tissues were significant independent prognostic factors of PSA recurrence. This is the first report demonstrating in patients with prostate cancer and the particular role of Akt-1 isoform expression as a prognostic marker depending of its localisation.
Le Page
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C
Département d'urologie, Centre de recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) and Institut du cancer de Montréal, Hôpital Notre-Dame, Quebec, Canada.
Koumakpayi
I H
IH
Alam-Fahmy
M
M
Mes-Masson
A-M
AM
Saad
F
F
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020033:Protein Isoforms / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D020033:Protein Isoforms; D051057:Proto-Oncogene Proteins c-akt; D017430:Prostate-Specific Antigen