SHORT-TERM CELLULAR EFFECTS INDUCED BY CASTRATION THERAPY IN RELATIONTO CLINICAL OUTCOME IN PROSTATE-CANCER

To explore the relationship between short-term effects oi castration t herapy and clinical response, biopsies obtained before and a week alte r castration therapy from 15 responding and 13 non-responding patients with prostate cancer were investigated, The biopsies were assessed fo r regressive morphology, apoptotic index by morphological criteria, nu clear area, and immunoreactivity (IR) for Ki-67, p53, bcl-2, bar and F as. The index was defined as the percentage of immunoreactive cells in a tumour. Regressive morphology was observed in 14 out of 15 respondi ng tumours after therapy, compared with 4 out of 13 non-responders (P < 0.001). Median tumour epithelial cell nuclear area and Ki-67 index d ecreased equally in both groups. The median apoptotic index increased from 2.6 to 3.5 after castration among responders (P < 0.05), whereas it remained al 2.8 among non-responders, p53 IR was present in three r umours before castration; after therapy p53 reactivity was seen in thr ee additional tumours belonging to the responding group. Median bcl-2 index increased in responders from 1.5 to 10.0 (P < 0.05), and in non- responders from 0.08 to 2.7 (P < 0.05). Bar IR and Fas IR were present in ail tumours before therapy and unchanged after therapy, Thus, regr essive morphology and an increase in apoptotic index were related to a favourable clinical response. These data suggest that it might be pos sible to predict the effect of castration therapy by examining tumour biopsies shortly after treatment.