High grade prostatic intraepithelial neoplasia in military working dogs with and without prostate cancer.

Abstract

High grade prostatic intraepithelial neoplasia (PIN) is the most likely precursor of human prostate cancer and is commonly found in men undergoing prostatic needle biopsy for suspected cancer. Recent work has demonstrated that pet dogs, like humans, develop PIN spontaneously and in association with prostate cancer. Pet dogs are the most domesticated animal, sharing the habitat and oftentimes the diet of their owners. If PIN and prostate cancer are strongly related to environmental factors, then the prevalence of these findings might differ in a population of dogs such as military working dogs which is not exposed to the habitat and diet of humans. In this study, we determined the prevalence of PIN in prostates of aged military working dogs with and without prostatic adenocarcinoma. Cases were selected from the military working dog slide and tissue archive at the Armed Forces Institute of Pathology, Washington, DC. The most recent 329 necropsies (1991 to 1996) were examined histologically by multiple reviewers; of these, 199 dogs (60%) were found to have evaluable prostatic tissue. In addition, the most recent 50 necropsies (1958 to 1996) with the diagnosis of prostatic cancer were examined, of which 25 cases (50%) were found to have evaluable prostatic adenocarcinoma. In most cases, a single large transverse section of prostatic tissue was available for review. Medical records for each dog were reviewed independently, and age, clinical history, indications for euthanasia, and other health problems were recorded. High grade PIN was identified in 3% of dogs (6 of 199 dogs) without prostate cancer. A total of 50.8% of dogs in this study group (101 of 199 dogs) were known to be sexually intact, 26.7% of dogs (53 of 199 dogs) were castrated, and the status of the remaining 22.6% of dogs (45 of 199 dogs) was unknown. High grade PIN was present in 18 of 25 dogs (72%) with prostatic adenocarcinoma. Of these cases, 11 dogs (44%) were castrated, 4 dogs (16%) were intact, and the status of 10 dogs (40%) dogs was unknown. Gleason scores ranged from 6 to 10, with a mean of 8.4 and a median of 8. High grade PIN is present in a small but substantial number (3%) of military working dogs. Of military working dogs with prostatic adenocarcinoma, 72% had high grade PIN. The true prevalence in each of these cohorts is likely to be higher given the sampling variation inherent in evaluating a single random histologic section. Aged male dogs seem to have substantial clinical utility as an animal model for prostatic carcinogenesis. We recommend that serial sectioning and total embedding of the prostate should be used to more thoroughly characterize premalignant and malignant diseases in aged military working dogs. This method will provide important data to determine whether a model of spontaneous PIN in elderly dogs may have clinical utility in developing strategies directed toward preventing and treating prostate.