Kreisberg JI et al. (2004) Phosphorylation of Akt (Ser473) is an excellent predictor of poor clinical outcome in prostate cancer. Cancer Research 64: 5232–5236

Improved diagnostic methods are urgently needed in order to avoid the unnecessary treatment of men with less aggressive prostate cancer. Kreisberg and colleagues have previously demonstrated increased phosphorylation (activation) of the protein kinase Akt, as well as decreased phosphorylation of extracellular signal-regulated kinase (ERK), in high-Gleason grade prostate tumors. This prompted them to investigate whether these biomarkers can be used to predict clinical outcome.

Prostate tumors were stained immunohistochemically for phosphorylated Akt (pAkt) and phosphorylated ERK (pERK). Degree of staining, measured on a scale of 0–300, was compared between tumors from cases of PSA failure (a surrogate for 'poor' outcome) and non-failure (a surrogate for 'good' outcome).

pAkt staining was significantly stronger in the 37 PSA failures than in the 16 non-failures (222.18 ± 33.9 vs 108.79 ± 104.57; P < 0.001). In contrast, pERK staining was weaker in the PSA failures than in the non-failures, although this difference was not statistically significant. The area under the ROC curve for pAkt and pERK predicting PSA failure was 0.84, indicating excellent discrimination. Gleason score at prostatectomy was not predictive of PSA failure in this study, even though Gleason grading is commonly used to predict clinical outcome.

The authors conclude that increased pAkt, with or without decreased pERK, is highly predictive of PSA failure in prostate cancer patients, and so warrants further investigation as a useful biomarker of clinically aggressive disease.