Short-term cellular effects induced by castration therapy in relation to clinical outcome in prostate cancer.
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.
Stattin
P
P
Department of Urology & Andrology, Umeå University, Sweden.
Westin
P
P
Damber
J E
JE
Bergh
A
A
D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D002455:Cell Division; D002467:Cell Nucleus / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000628:therapy*; D011518:Proto-Oncogene Proteins / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000032:analysis
C494826:BAX protein, human; D015415:Biomarkers; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019014:fas Receptor