This competing renewal application (Diagnostic Center) is for a UO1 grant in response to RFA DK94-18. The investigators describe the widespread economic and medical problems associated with benign prostatic hyperplasia. The overall goal of the study is to test the effectiveness of pharmacological intervention in benign prostatic hyperplasia (BPH) with the hope that pharmacological intervention may prove to be superior to surgery for some patients. The goal of the project under consideration from the University of Colorado is to establish the requested Diagnostic Center for the full-scale trial. The Diagnostic Center will perform assays on peripheral blood with materials sent from several clinical centers; these assays will include prostate specific antigen, luteinizing hormone, testosterone, and dihydrotestosterone. Blood chemistries will be carried out initially and annually for the duration of the trial (described in Appendix F of the protocol). The Diagnostic Center will receive four fixed and two frozen, 18-gauge needle biopsies from each patient entered into the study. A series of slides made from the paraffin-embedded fixed needle biopsies and from the frozen needle biopsies will be examined. These slides will be examined for diagnostic purposes by the principal investigator and an unidentified fellow who will be appointed in the second year of support. Sets of slides will also be made available to the departments of pathology from the hospitals from which the biopsies are obtained. The pathology analyzed in the Diagnostic Center in Denver will be recorded on a standard form that is displayed in the material sent with the application. Additional sections of paraffin-embedded needle biopsies and the remaining materials from frozen needle biopsies will be stored for research in the future. Biopsies will be carried out at the beginning of the study, after one year, and at the end of the study. In addition to the above, immunohistochemical studies will be carried out to assess the expression of prostate specific antigen and the MIB-1 nuclear proliferation antigen. Apoptosis will be evaluated with the TUNEL immunohistochemical technique. Morphometric evaluations will be carried out """"""""using a semiautomated image analysis approach such as that described by Shapiro et al (44)."""""""" The step by step methods of staining are listed. The investigators state that conditions stipulated in the pilot study that was carried out in their center made in """"""""impossible...to have any information about the expected ranges of variation for each of the variables with respect to any measures of treatment outcome...From the published literature, however, it is expected that data on 280 patients will be sufficient to produce meaningful results."""""""" They state that a """"""""...subset of approximately 280 cases will have detailed analyses performed.""""""""
