Purpose: The overarching goal of the grant is to characterize molecular heterogeneity in multi-focal and metastatic prostate cancer. Aim 1 focuses on a 4-gene signature of prostate cancer prognosis, and whether the signature differs across within-patient tumor nodules. Aim 2 compares gene expression profiles between primary and lymph node metastases in order to identify genes involved in metastatic progression of prostate cancer. Scope: In year 1, Dr. Batista has received IRB approval, completed a series of courses to augment her expertise in prostate cancer epidemiology, has coordinated meetings to discuss the study progress with collaborators, and has begun specimen and data collection for the proposed work. In the upcoming year 2, Dr. Batista will complete data collection, lead the statistical analyses, and publish the findings in peer-reviewed journals. Major Findings: To date, the proposed biomarkers are in the process of being measured. In a related analysis of tumor expression of prostate-specific membrane antigen (PSMA) and prostate cancer-specific mortality, Batista et al. found that PSMA was positively correlated with Gleason score and tumor angiogenesis, but was not an independent predictor of prostate cancer survival (Cancer Epidemiol Biomarkers Prev, in press). Significance: The clinical significance of the project is to better characterize putative prognostic markers for prostate cancer, as well as identify potential therapeutic targets for secondary prevention.