This grant application seeks to establish DNA flow cytometric (FCM) information about ploidy and proliferation of localized and disseminated prostate cancer. These FCM findings will be related to detailed clinical and pathologic information about these patients and to results from image cytometry and molecular analysis of specific target genes. Our underlying hypothesis is that the more abnormal the genetic makeup of the tumor is, the more abnormal the FCM results win be and the worse the prognosis. With this in mind we will sort diploid and aneuploid cells from aneuploid tumors and submit them separately to molecular analysis. Proliferation will be determined by computer curve fitting routines to estimate S phase fractions. Further selection criteria will be based on two parameter FCM analysis using DNA FCM and a fluorescent antibody procedure against the protein product of the p53 tumor suppressor gene. Coordinated FCM sorting and molecular studies will be employed to determine whether these two parameter FCM studies can be successfully employed to enrich the molecular studies for samples having genetic abnormalities in the p53 gene. The prognostic implications of abnormal ploidy in benign prostate tissue associated with prostate cancer will be similarly analyzed. Three groups of patients will be followed: those with localized disease treated surgically, those with localized disease treated by definitive radiation therapy and those with metastatic disease treated by hormonal ablation. During the course of this grant proposal we should be able to obtain statistical evaluations of the answers to the following questions: 1. Are the prognostic implications of aneuploidy in localized prostate cancer different in patients treated by definitive radiation therapy and in patients undergoing radical retropubic prostatectomy? 2. Can we identify the subset of those with diploid localized prostate cancer whose disease has a high probability of progression? 3. Will a combination of flow and image cytometry and/or molecular studies better describe the course of disease for these patients than will any single study? 4. Do flow and image cytometry provide equivalent results in most cases? 5. Are there instances where one or another or a combination of these cytometric studies will provide better descriptors of the disease status for these patients?
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