Prostatic intraepithelial neoplasia occurs spontaneously in the canine prostate.

Abstract

Prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer. Although the dog is the only non-human species in which spontaneous prostate cancer occurs frequently, the prevalence of PIN in the canine prostate is unknown. A naturally occurring animal model of PIN has not been described. To determine if high grade PIN occurs spontaneously in the canine prostate, we evaluated totally embedded prostates from 35 outbred dogs that had no clinical evidence of prostatic disease. Prostates from three groups of dogs were analyzed: (1) 11 sexually intact dogs 7-17 years old (elderly sexually intact); (2) 13 sexually intact dogs 1-4 years old (young sexually intact); and (3) 11 dogs 7-17 years old that had been castrated (elderly castrated). The prevalence of PIN was determined by systematic evaluation of hematoxylin/eosin and high molecular weight keratin 34 beta-E12 stained tissue sections from formalin-fixed, paraffin embedded prostates that had been serially sectioned at 4 mm intervals. Canine high grade PIN showed cytologic features identical to the human counterpart, including cell crowding, loss of polarity, and nuclear and nucleolar enlargement. Foci of high grade PIN were present in the prostates of 6 of 11 (55%) elderly, sexually intact dogs but only 1 of 13 (8%) dogs less than 4 years old. Foci of high grade PIN were detected in 1 of 11 (9%) elderly castrated dogs. In elderly, sexually intact dogs with PIN, foci of high grade PIN were present in 13 of 83 (16%) tissue sections evaluated; one of these dogs had focal adenocarcinoma in addition to PIN. These results indicate that high grade PIN is frequently present in the prostate of elderly, sexually intact dogs. The prevalence of canine PIN, like human PIN, is apparently influenced by age and testicular androgens. The canine prostate may serve as a useful model to determine the factors that regulate the apparent progression from benign epithelium to PIN and invasive carcinoma.