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 clinically indolent prostate cancer. Kreisberg and colleagues have previously demonstrated increased phosphorylation (activation) of the protein kinase Akt, as well as decreased phosphorylation (inactivation) 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 (detectable and rising PSA; a surrogate for ‘poor’ outcome) and non-failure (undetectable PSA 5 years after prostatectomy; 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 very good 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.
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Predicting clinical outcome in prostate cancer. Nat Rev Clin Oncol 1, 11 (2004). https://doi.org/10.1038/ncpuro0020x