EFFECTS OF COMBINATION ENDOCRINE TREATMENT ON NORMAL PROSTATE, PROSTATIC INTRAEPITHELIAL NEOPLASIA, AND PROSTATIC ADENOCARCINOMA

Aims-To investigate the effect of combination endocrine treatment (CET ) or luteinising hormone releasing hormone agonist and flutamide on no n-neoplastic prostate, prostatic intraepithelial neoplasia, and prosta tic adenocarcinoma. Methods-The morphology, including the mitotic acti vity, of 12 radical prostatectomies from patients with prostatic adeno carcinoma pretreated for three months with CET was evaluated in haemat oxylin and eosin stained sections and compared with an untreated age a nd stage matched control group. Results-A differential effect on the n onneoplastic prostate was observed. In fact, the transition zone of th e treated prostate showed simplification of the glandular lobules: the ducts and acini were small without undulations of the epithelial bord er and with a prominent basal cell layer. Within the peripheral zone t here was inconspicuous branching of the ducts and acini which looked d ilatated and lined by flattened atrophic epithelium. Prostatic intraep ithelial neoplasia occurred in scattered ducts and acini in the periph eral zone of 10 of the 12 patients. The epithelial cell lining showed a prominent basal cell layer. A certain degree of secretory cell type stratification was always present, However, crowding was less evident than in the untreated prostate because of cytoplasmic clearing and enl argement as a result of coalescence of vacuoles. The treated adenocarc inomas had neoplastic acini which looked small and shrunken, and areas of individual infiltrating tumor cells separated by abundant intergla ndular connective tissue. The secretory cells of non-neoplastic, prost atic intraepithelial neoplasia, and prostatic adenocarcinoma lesions h ad inconspicuous nucleoli, nuclear shrinkage, chromatin condensation, and cytoplasmic clearing. Apoptotic bodies were easily identifiable in all the cell layers. The lumina were rich in macrophages, sloughed se cretory cells with degenerative features, and apoptotic bodies. Mitose s were not observed in any of the treated non-neoplastic prostate, pro static intraepithelial neoplasia, or prostatic adenocarcinomas, wherea s the mitotic frequency increased from non-neoplastic prostate through prostatic intraepithelial neoplasia up to prostatic adenocarcinomas i n the untreated specimens. Conclusions-CET before radical prostatectom y causes regressive epithelial changes together with enhanced apoptosi s and blocked mitotic activity.