Role of canine basal cells in postnatal prostatic development, induction of hyperplasia, and sex hormone-stimulated growth;; and the ductal origin ofcarcinoma (vol 47, pg 149, 2000)

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 do gs and unlike the disease in humans, it occurs with relatively high frequen cy in castrated animals. Since basal cells are thought to be key participan ts in normal and abnormal growth of the human gland, we used immunohistoche mistry to investigate the role that they may play in canine prostatic devel opment, the evolution of hyperplasia and carcinoma, and the effects of sex hormones 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 from 19 dogs with prostatic carcinoma. In add ition, we also studied the prostates from two intact dogs treated with 5 al pha -dihydrotestosterone (DHT) for 6 months and two castrated dogs that wer e subsequently treated with 5 alpha -androstane-3 alpha diol and estradiol- 17 alpha, as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cyt okeratin (HMC), pancytokeratin, androgen receptor (AR), and the proliferati ve marker KI-67. RESULTS. We 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 acini were discontinuous. Populations of both basal cell types were variabl y AR positive, but while HMC immunostaining was abolished in acinar cells f ollowing long-term castration, staining remained in ductal cell counterpart s. Paralleling the histological development of hyperplasia, the acinar basa l cell population increased with age and were the major cell type that expr essed KI-67. In contrast, ductal basal cell populations did not expand in t he prostates of older dogs and were seldom positively stained for KI-67. Th e numbers of HMC and KI-67-stained acinar basal cells were dramatically inc reased in the prostates of intact dogs treated with DHT when compared with glands of untreated controls. This was not the case with ductal basal cells . Androgens given alone or together with estrogen to castrated dogs induced widespread HMC and KI-67 immunostaining in both populations of basal cells . In addition, our results indicate that the majority of canine prostatic c arcinomas likely arise exclusively from ductal epithelium. Only one of the 19 cases of carcinoma contained cells that expressed AR, which suggests tha t androgens may not be required for the initiation or progression of these cancers. CONCLUSIONS. Our findings indicate that two biologically distinct populatio ns of basal cells may 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 dog likely arises from ductal cells. Taken together, these findings may ind icate that canine acinar basal cells and ductal epithelium have separate su sceptibilities to factors that promote hyperplastic or neoplastic developme nt.