The utility of intracellular markers and analytical cytometric methods in the classification of human prostatic cancers will be examined. The markers to be evaluated include cellular DNA content (for assessment of cell proliferation and DNA aneuploidy), protoncogenes, and a panel of nuclear antigens. The nuclear antigens will be evaluated using a panel or monoclonal antibodies having cell proliferation-associated antigen expression and/or specificities to different nuclear substructures including the nucleolus, heterochromatin, interchromatin granules, euchromatin and perinuclear regions. Using multiparameter flow cytometric analysis of both the total cells from both primary tumors and their metastases, as well as relevant cell subpopulations, in conjunction with both prospective and retrospective studies, the utility of these antigens in predicting clinical prognosis will be ascertained in prostatic cancer. To further investigate the expression of these markers, control investigations will be performed using in vitro prostatic cell lines including primary lines and metastatic variants. Using these lines, marker expression will be evaluated under conditions of varying cellular proliferation and differentiation. Finally, using the cell sorting capacity of the flow cytometer, cell subpopulations (e.g. aneuploid cells) which correlate with more aggressive tumor behavior will be sorted and examined for possible protein differences from other tumor subpopulations using 2-D electrophoresis. If unique proteins are observed in relevant tumor subpopulations, we will attempt to develop additional monoclonal antibodies for these studies, using the identified protein as immunogen. It is hoped that the proposed studies will lead to a better understanding of primary and metastatic prostatic cancer, and possibly provide the basis for defining more accurately those patients most likely to benefit from experience mental therapies.
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