PROSTATIC INVASIVE ADENOCARCINOMA - EFFECT OF COMBINATION ENDOCRINE THERAPY (LHRH AGONIST AND FLUTAMIDE) ON THE EXPRESSION AND LOCATION OF PROLIFERATING CELL NUCLEAR ANTIGEN (PCNA)

Expression and location of Proliferating Cell Nuclear Antigen immunost aining in epithelial nuclei were assessed on histological sections fro m 32 cases of invasive adenocarcinoma of the prostate gland: 20 untrea ted and 12 treated with combination endocrine therapy or CET. The PCNA -positive nuclei showed homogeneous or granular types of staining or a mixture of both, and a gradation in the intensity of staining. Nuclei with homogeneous patterns appeared darker brown than the lighter gran ular and mixed patterns. Darker nuclei were more frequently noted, mai nly among the epithelial cells adjacent to the stroma, in the untreate d cases. In contrast, nuclei with pyknotic chromatin, unstained and co rresponding to apoptotic bodies, were move frequently seen in the trea ted patients. For the untreated invasive adenocarcinomas, the mean pro portion of PCNA-stained epithelial nuclei in the 10 cases with an acin ar pattern (small and large) was 8.86% (SE 0.23%). The mean value in t he 5 cases with a cribriform pattern was 11.76% (SE 0.52%), that is, g reater than in the acinar pattern, and decreased from the nuclei in th e basal position, or adjacent to the stroma, toward the lumen: 14.40% (SE 0.61%) in the basal position, 11.84% (SE 1.30%) in the intermediat e and 9.26% (SE 0.66%) in the lumenal. In the 5 cases with a solid/tra becular pattern, the proportion of PCNA-positive nuclei was 15.74% (SE 2.30%), that is, higher than in all the other patterns, and decreased from the cell layer adjacent to the stroma (17.60%, SE 2.92%) toward the other layers (13.88%, SE 1.71%). For the treated invasive adenocar cinomas, the proportions of PCNA-stained epithelial nuclei were much l ower than in the untreated ones, the difference being statistically hi ghly significant: 1.59% (SE 0.18%) in the 7 cases with an acinar patte rn, 1.53% (SE 0.56%) in the 4 cribriform cases - 2.41% (SE 0.86%) in t he basal position, 1.20% (SE 0.33%) in the intermediate and 0.37% (SE 0.52% in the lumenal - and 0.89% in the case with solid/trabecular pat tern - 0.99% in the cell layer adjacent to the stroma and 0.79% in the other layers. In conclusion, our investigation pointed out that combi nation endocrine therapy induces tumour regression by two possible mec hanisms, one related to the enhancement of the apoptotic phenomenon an d the other greatly reducing the proliferation activity.