From gene to clinic: TMA-based clinical validation of molecular markers in prostate cancer

Current high-throughput screening techniques using DNA arrays have identified hundreds of new candidate biomarkers for diagnosis and risk prediction of prostate cancer. Large-scale analysis of clinical prostate cancer specimens is a key prerequisite for the validation of these genes. We have constructed a tissue microarray from more than 2,500 prostate cancers with full histo-pathological and clinical long-term follow-up data and analyzed expression and gene copy number patterns of 16 different candidate markers for their ability to predict prostate cancer progression and patient prognosis. The best candidates were used to extend established clinical prediction tools (nomograms) that were based on nonmolecular data only, such as prostate-specific antigene (PSA), clinical stage, and histological grading (Gleason grade). Using this approach, we could identify ANXA3 as an independent marker, which was capable of increasing the accuracy of the clinical nomogram, thereby fulfilling the criteria of a novel prognostic prostate cancer marker. This approach of integrating large-scale clinical and molecular variables may provide a new paradigm for the use of molecular profiling to predict the clinical outcome in prostate cancer.