Background: Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation.
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The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation.
Methods: Prostatectomy samples from a large patient cohort with long follow-up were blindly assessed by expert pathologists who identified the tissue regions with the highest and lowest Gleason grade from each patient. To simulate biopsy-sampling error, a core from a high- and a low-Gleason area from each patient sample was used to generate a 'high' and a 'low' tumour microarray, respectively.
Results: Using a quantitative proteomics approach, we identified from 160 candidates 12 biomarkers that predicted prostate cancer aggressiveness (surgical Gleason and TNM stage) and lethal outcome robustly in both high- and low-Gleason areas. Conversely, a previously reported lethal outcome-predictive marker signature for prostatectomy tissue was unable to perform under circumstances of maximal sampling error.
Conclusions: Our results have important implications for cancer biomarker discovery in general and development of a sampling error-resistant clinical biopsy test for prediction of prostate cancer aggressiveness.
Shipitsin M, Small C, Choudhury S, Giladi E, Friedlander S, Nardone J, Hussain S, Hurley AD, Ernst C, Huang YE, Chang H, Nifong TP, Rimm DL, Dunyak J, Loda M, Berman DM, Blume-Jensen P. Are you the author?
Metamark Genetics Inc., Cambridge, MA 02142, USA; Department of Pathology, Yale University Medical School, New Haven, CT 06520, USA; Department of Pathology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA; Department of Pathology and Molecular Medicine and Queen's Cancer Research Institute, Queen's University, Kingston, ON, Canada K7L 3N6.
Reference: Br J Cancer. 2014 Jul 17. Epub ahead of print.