Prognostic importance of androgen receptors in epithelium and stroma in early stage prostate cancer [ 2005 - 2007 ]

Research Grant

Researchers: A/Pr David Horsfall (Principal investigator) ,  Dr Carmela Ricciardelli ,  Prof Villis Marshall ,  Prof Wayne Tilley

Brief description The use of serum prostate specific antigen (PSA) to screen asymptomatic men for prostate cancer has reduced the stage of disease at diagnosis. The majority of tumours are now small and potentially organ-confined. The use of nomograms, algorithms based on preoperative clinical features of these patients (serum PSA level, Gleason grade, clinical stage) has facilitated this process, but is imperfect as 20-30% of patients experience disease relapse within 5-7 years. Tumours with similar preoperative clinical features have markedly different outcomes, reinforcing the inadequacy of current approaches to determining whether or not an individual patient has organ-confined disease. A new approach is to incorporate into the standard diagnostic nomograms, biological features from preoperative core biopsy linked to the process of disease relapse, and which independently predict patient outcome risk group. Our preliminary studies using a small hypothesis-generating cohort of patients with early stage prostate cancer determined that elevated levels of androgen receptors (AR) in malignant epithelial cells and reduced levels of AR in peritumoral stromal cells independently predict disease relapse after surgery. In this project, AR measurements will be analysed in independent cohorts of patients derived from two Australian institutions to determine whether the predictive value is maintained across multi-Institutional cohorts. Selected androgen-regulated markers of tumour growth and spread (proliferative, apoptotic, metastatic) will be examined in microarrayed postoperative tissue samples. The postoperative markers will be examined for independence of prediction of relapse. Independent markers will be examined for ability to increase predictive efficacy in standard diagnostic nomograms. Levels of the two markers with greatest predictive value will be measured in preoperative core biopsies and tested for predictive ability as a prelude to clinical practice.

Funding Amount $AUD 348,750.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant