Accurate characterization of prostate cancer remains a major problem in the clinical management of individual prostate cancer patients and in monitoring clinical trials of emerging therapies. High Resolution - Magic Angle Spinning (HR-MAS) spectroscopy is a non-destructive ex vivo technique that can provide a full chemical analysis of intact prostate tissues prior to a complete histopathologic, immunohistochemical and genetic analysis of the exact same tissue. In this project we will use the high specificity of combined in vivo MRI/MRSI for identifying prostate cancer to target prostate biopsy and surgical tissues in 250 patients prior to therapy and 125 patients demonstrating biochemical failure (rising PSA) and MRI/MRSI evidence of recurrent disease after hormone deprivation therapy for subsequent ex-vivo analyses. The goal of this proposal is to establish a database correlating metabolic profiles associated with specific prostate tissue types, grades of prostate cancer, and response to hormone deprivation therapy and to begin correlating pre-therapy metabolic profiles with gene expression profiles. Using this correlative data we wish to test the following hypotheses: (1) That distinctive metabolic profiles can be associated with the following pathologic prostate tissue types predominatly glandular and stromal healthy peripheral zone tissues, predominatly glandular and stromal benign prostatic hyperplasia, cancers of increasing Gleason score, prostatic intraepithelial neoplasia (PIN), prostatic inflammatory atrophy (PIA) and prostatitis. (2) The dramatic decreases in prostate citrate levels with prostate cancer evolution, progression, and in response to hormone deprivation therapy are associated with changes in morphology (reduction in glandular tissue), prostatic Zn concentration, and/or expression of key Kreb cycle enzymes. (3) Elevated concentrations of phospholipid metabolites (glycerophosphocholine, phosphocholine and choline) in prostate cancer prior to and after therapy are associated with changes in morphology (increased malignant epithelial cell density) and/or changes in cellular proliferation and apoptosis. (4) The dramatic decrease in prostatic spermine concentration with prostate cancer evolution, progression and in response to hormone deprivation therapy is associated with changes in its secretion (reduction in glandular tissue), and/or changes in cellular proliferation and apoptosis. (5) That distinctive metabolic profiles can be associated with the over- and/or under-expression of specific genes categorized by the following pathologic criteria, predominatly stromal versus predominatly glandular healthy tissue, healthy tissue versus prostate cancer, and cancer having Gleason Score equal to or less than 6 versus cancer having a Gleason Score equal to or greater than 7. This work should result in improved interpretation of patient MRSI data, and provide data on how HR-MAS metabolic profiles can compliment the pathologic and genetic assessment of prostate cancer prior to and after hormone deprivation therapy.
