PROSTATIC INTRAEPITHELIAL NEOPLASIA OCCURS SPONTANEOUSLY IN THE CANINE PROSTATE

Purpose: Prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer. Although the dog is the only non-h uman species in which spontaneous prostate cancer occurs frequently, t he prevalence of PIN in the canine prostate is unknown. A naturally oc curring animal model of PIN has not been described. Materials and Meth ods: To determine if high grade PIN occurs spontaneously in the canine prostate, we evaluated totally embedded prostates from 35 outbred dog s that had no clinical evidence of prostatic disease. Prostates from t hree groups of dogs were analyzed: (1) 11 sexually intact dogs 7-17 ye ars old (elderly sexually intact); (2) 13 sexually intact dogs 1-4 yea rs old (young sexually intact); and (3) 11 dogs 7-17 years old that ha d been castrated (elderly castrated). The prevalence of PIN was determ ined 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. Results: Canine high grade PIN showed cytologic features i dentical to the human counterpart, including cell crowding, loss of po larity, and nuclear and nucleolar enlargement. Foci of high grade PIN were present in the prostates of 6 of 11 (55%) elderly, sexually intac t 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 eld erly, sexually intact dogs with PIN, foci of high grade PIN were prese nt in 13 of 83 (16%) tissue sections evaluated; one of these dogs had focal adenocarcinoma in addition to PIN. Conclusions: These results in dicate that high grade PIN is frequently present in the prostate of el derly, sexually intact dogs. The prevalence of canine PIN, like human PIN, is apparently influenced by age and testicular androgens. The can ine prostate may serve as a useful model to determine the factors that regulate the apparent progression from benign epithelium to PIN and i nvasive carcinoma.