Role of canine basal cells in prostatic post natal development, induction of hyperplasia, sex hormone-stimulated growth; and the ductal origin of carcinoma

BACKGROUND. The canine prostate has often been proposed as a model for abno rmal growth of the human gland. Hyperplasia of the prostate is common in ag ing men and has been estimated to be present in 100% of old intact dogs. Wh ile prostatic carcinoma is common in older men it appears to be rare in dog s and unlike the disease in humans it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemi stry to investigate the role that they may play in canine prostatic develop ment, the evolution of hyperplasia and carcinoma, and the effects of sex ho rmones on these cells. METHODS. Prostate specimens were obtained at autopsy from seven sexually im mature dogs, autopsy and biopsy samples from 14 sexually mature intact anim als, from four castrates, and from19 dogs with prostatic carcinoma. In addi tion, we also studied the prostates from two intact dogs treated with 5 alp ha -dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5 alpha -androstane-3 alpha diol and estradiol-1 7 alpha. as well as specimens from two sexually ablated animals given DHT f or 2 weeks. All specimens were immunostained for high molecular weight cyto keratin (HMC), Pancytokeratin, androgen receptor (AR), and the proliferativ e marker KI-67. RESULTS. Wa find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC stain ing, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer whereas those lining a cini were discontinuous. Populations of both basal cell types ere variably AR positive but while HMC immunostaining was abolished in acinar cells foll owing long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal c ell population increased with age and were the major cell type that express ed KI-67. in contrast, ductal basal cell populations did not expand in the prostates of older dogs and were seldom positively stained for KI-67. The n umbers of HMC. and KI-67-stained acinar basal cells were dramatically incre ased in the prostates of intact dogs treated with DHT when compared with gl ands of untreated controls. This was not the case with ductal basal cells. Androgens given alone or together with estrogen to castrated dogs induced w idespread HMC and KI-67 immunostaining in both populations of basal cells. In addition, our results indicate that the majority of canine prostatic car cinomas likely arise exclusively from ductal epithelium. Only one of the 19 cases of carcinoma contained cells that expressed AR which suggests that a ndrogens ma; not be required for the initiation or progression of these can cers. CONCLUSIONS. Our findings indicate that two biologically distinct populatio ns of basal cells mall exist in the canine prostate. In this regard the age -related expansion of proliferating acinar basal cell populations, probably mediated by sex steroids, is a key factor in the pathogenesis of canine pr ostatic hyperplasia. Additionally we find that prostatic carcinoma in the d og likely arises from ductal cells. Taken together these findings may indic ate that canine acinar basal cells and ductal epithelium have separate susc eptibilities to factors that promote hyperplastic or neoplastic development . Prostate 47:149-163, 2001. (C) 2001 Wiley-Liss, Inc.