Cycling activity of benign prostatic epithelial cells during long-term androgen blockade: Evidence for self-renewal of luminal cells

Combined androgen blockade (CAB) therapy (LHRH agonist and flutamide) for 6 month leads to marked regressive changes of the prostate gland. This is as sociated with a reduction in the ratio of luminal to basal cells in the per ipheral zone (PZ) in hyperplastic glands of the transitional zone (TZ). To examine the cycling activity of luminal and basal cells, double immunostain ing was performed. For precise definition of basal cells, the basal cell-sp ecific antibody 34 beta E12 was used, while cycling cells were identified b y the MIB-1 antibody. In 6-month-treated specimens. the fraction of cycling luminal cells increased from 0.3 to 2.5 per cent in the PZ and from 0.2 to 3.9 per cent in the TZ, This was associated with an inversion of the ratio of MIB-1-labelled luminal to basal cells, with values of 5.7:1 (PZ) and 3. 9:1 (TZ), compared with 1:4 (PZ) and 1:5 (TZ) in untreated specimens. The p redominance continued for at least 11 years of CAB. The findings strongly s uggest that luminal cells are capable of self-renewal under conditions of l ow androgen levels. The substantial decrease of prostatic volume on long-te rm CAB implies that cell loss outweighs cell proliferation. (C) 1998 John W iley & Sons, Ltd.