Apoptosis in prostate carcinomas after short-term treatment with decapeptyl.

Abstract

Altogether, 40 patients with advanced prostate cancer received the LH-RH analog, Decapeptyl (D), as monotherapy for 1 month. The dose of D was 3.75 mg/month, intramuscularly in microcapsules. Needle biopsy was taken from the prostate of 20 patients at 24 hours, of 10 patients at 7 days, and of 10 patients at 30 days after the injection. The biopsy samples were investigated for mitotic and apoptotic indices as well as expression of p53 and Ki67 in the tumor cells. The effect of the LH-RH analog was manifested in very low and even absent mitotic activity in all points in time. The expression of mutant p53 was high (above 80%) in all 1-day and 7-day samples and in 8 of 10 samples taken 30 days after the start of the therapy. In 2 cases, the ratio of p53-expressing tumor cells was 2% and 5%. At day 30, the previously high ratio of Ki67-positive tumor cells decreased to 2-10% in 8 cases and showed focally higher values (70-90%) in 2 cases. Extremely high (90-100%) apoptosis could be registered in scattered foci of the tumor tissue in all samples taken 1 and 7 days after D injection. The other parts of the tumor tissue showed lower (1-5%) apoptotic activity. At day 30 after the injection, the same phenomenon was observed in 4 cases, but in 6 cases the apoptotic ratio became diffusely low (1-2%). Focal increase of apoptosis observed in the 1- and 7-day samples may be attributed to the direct effect of the LH-RH analog on tumor cells. The findings at day 30 indicate a considerable decrease in proliferating activity and, in the majority of cases, also in apoptotic activity, reflecting the effect of D on the pituitary-gonadal axis.