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

• Published in: The Prostate 2001-05, Vol.47 (3), p.149-163
• Main Authors: Leav, Irwin, Schelling, Kimberly H., Adams, Jason Y., Merk, Frederick B., Alroy, Joseph
• Format: Article
• Language: English
• Subjects: adenocarcinoma; Adenocarcinoma - pathology; Androstane-3,17-diol - analogs & derivatives; Androstane-3,17-diol - pharmacology; Animals; basal cell proliferation; Biological and medical sciences; canine prostate; Cell Division - physiology; Dihydrotestosterone - pharmacology; Disease Models, Animal; Dog Diseases - pathology; Dogs; Estradiol - pharmacology; Gonadal Steroid Hormones - physiology; Gynecology. Andrology. Obstetrics; hyperplasia; Immunohistochemistry; Keratins - metabolism; Ki-67 Antigen - metabolism; Male; Male genital diseases; Medical sciences; Orchiectomy; Prostate - cytology; Prostate - drug effects; Prostate - pathology; Prostatic Hyperplasia - pathology; Prostatic Neoplasms - pathology; Receptors, Androgen - metabolism; response to sex steroids; Tumors
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.1058

BACKGROUND The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men it appears to be rare in dogs 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 immunohistochemistry to investigate the role that they may play in canine prostatic development, 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 immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5α‐dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5α‐androstane‐3α diol and estradiol‐17α as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), Pancytokeratin, androgen receptor (AR), and the proliferative 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 staining, 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 variably AR positive but while HMC immunostaining was abolished in acinar cells following long‐term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and were the major cell type that expressed 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 numbers of HMC and KI‐67‐stained acinar basal cells were dramatically increased 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 HM