MORPHOLOGIC AND IMMUNOHISTOCHEMICAL CHANGES IN PROSTATE-CANCER AFTER PREOPERATIVE HORMONAL-THERAPY - A COMPARATIVE-STUDY OF RADICAL PROSTATECTOMIES

Background. Estramustine phosphate (EMP) and flutamide (FL) were used as reversible preoperative hormonal drugs in the surgical treatment of patients with localized prostate cancer. Methods. The authors descrip tive and quantitatively examined the morphologic and immunohistochemic al changes in 40 of 200 step-sectioned radical prostatectomies, obtain ed after treatment with EMP (25 patients) and with FL (15 patients). O f these, 28 pretreatment needle core biopsies were available. Results. Every specimen contained adenocarcinoma. Understaging was found in 50 % of the cases and a higher Gleason score in 70%. Benign glands underw ent atrophy and squamous metaplasia. Treated tumors showed cytoplasmic vacuolization, nuclear pyknosis, fibrosis and lymphocytic infiltrates . The EMP group had an 84% (P < 0.05) higher mean total regression sco re than the FL group. Estramustine phosphate induced a 56% (P < 0.05) and a 34% decrease in tumoral prostate specific antigen and prostate s pecific acid phosphatase intensity scores, respectively, versus 29% an d 32% after FL. The mean proliferating cell nuclear antigen (PCNA) lab eling index and the mean mitotic index of the EMP group were 52% (P < 0.05) and 70% (P < 0.05) lower than those measured in the FL group. Ea ch FL-treated tumor and 92% of EMP-treated tumors expressed chromogran in A (ChrA); ChrA labeling correlated significantly with PCNA labeling . Seventy-six percent of EMP-treated specimens revealed venous thrombo sis. Conclusions. Estramustine phosphate induces important morphologic and immunohistochemical changes in prostate cancer with an apparent d ecrease of secretory and proliferative activity when compared with FL- treated tumors. These changes represent pitfalls in the diagnosis and grading of treated carcinomas. Nearly every treated adenocarcinoma of the prostate has neuroendocrine differentiation, showing increasing Ch rA labeling with higher tumor stage. A significant correlation between tumor proliferation and neuroendocrine differentiation was noticed in this small cohort of patients. There was a high incidence of peripros tatic venous after EMP treatment.