Prognostic Value of Akt-1 in Human Prostate Cancer: A Computerized Quantitative Assessment with Quantum Dot Technology

Background: Akt/protein kinase B signaling pathway has been implicated in tumorigenesis and progression. Previous studies showed the predictive potential of p-Akt-1, but total Akt-1 could provide more reliable information. We used image deconvolution, nanotechnology (quantum dots), and image analysis to improve Akt-1 quantification. Design: This tissue microarray study included 840 radical prostatectomy cases. Slides were incubated with primary antibody against nonphosphorylated Akt-1 (Akt-1) followed by biotinylated secondary antibody and then by Qdot655 streptavidin conjugate. Slides were imaged under fluorescence microscopy and spectral deconvolution (Nuance) and quantified using plug-in image analysis software. Average intensity of Akt-1 signal was measured and subject to statistical analysis. Multivariate analysis (Cox regression) was applied to assess the prognostic value of Akt-1 for biochemical recurrence and prostate cancer-specific death. Akt-1 expression was also examined for correlations with Ki-67 index and apoptotic index in our database. Result: Akt-1 was inversely correlated with apoptotic index (rho = -0.203; P = 0.004) but not with Ki-67 index. The correlation between Akt and p-Akt is significant but weak (P = 0.0496; R-2 = 0.118). On multivariate analysis Akt-1 was independently predictive of biochemical recurrence [hazard ratio, 2.863 (95% confidence interval, 1.127-7.271); P = 0.0270]. Akt-1 level is also predictive of prostate cancer-specific death (P = 0.0376). Conclusion: High levels of Akt-1, assessed by quantum dots, deconvolution imaging, and image analysis, are associated with a higher risk of biochemical recurrence and prostate cancer-specific death.