Short-term cellular effects induced by castration therapy in relation to clinical outcome in prostate cancer

Abstract

Summary To explore the relationship between short-term effects of castration therapy and clinical response, biopsies obtained before and a week after castration therapy from 15 responding and 13 non-responding patients with prostate cancer were investigated. The biopsies were assessed for regressive morphology, apoptotic index by morphological criteria, nuclear area, and immunoreactivity (IR) for Ki-67, p53, bcl-2, bax and Fas. The index was defined as the percentage of immunoreactive cells in a tumour. Regressive morphology was observed in 14 out of 15 responding tumours after therapy, compared with 4 out of 13 non-responders (P < 0.001). Median tumour epithelial cell nuclear area and Ki-67 index decreased 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 at 2.8 among non-responders. p53 IR was present in three tumours before castration; after therapy p53 reactivity was seen in three 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). Bax IR and Fas IR were present in all tumours before therapy and unchanged after therapy. Thus, regressive morphology and an increase in apoptotic index were related to a favourable clinical response. These data suggest that it might be possible to predict the effect of castration therapy by examining tumour biopsies shortly after treatment.

Decreased Pigment Epithelium-Derived Factor Is Associated with Metastatic Phenotype in Human and Rat Prostate Tumors

“…Human and rodent tumor tissue sections were deparaffinated and rehydrated, according to standard procedures, and washed with PBS. Immunohistochemical staining was performed using primary antibodies against pigment epithelium-derived factor (23), VEGF (Santa Cruz Biotechnology, Santa Cruz, CA; sc-507), Ki-67, endoglin, and factor VIIIrelated antigen (DAKO Corporation) as described (6,38,39). The slides were routinely counterstained with Meyer's hematoxylin solution and mounted.…”

C-Jun N-terminal kinase is required for phorbol ester- and thapsigargin-induced apoptosis in the androgen responsive prostate cancer cell line LNCaP

“…Consequently, removal of androgens induces rapid involution, mainly due to an increase in apoptosis Stattin et al, 1998). This is the basis for hormone ablation therapy in prostate cancer when the tumor is still hormone-dependent (Huggins and Hodges, 1941;Moore, 1994).…”

Early effects of pharmacological androgen deprivation in human prostate cancer

“…One possible explanation for these discrepancies might relate to the highly disparate nature of the cancers being treated. Thus, the present patients all had disease localized to the prostate, the biology of which is quite different from the predominantly advanced or metastatic disease treated by surgical castration [18,22,23].…”