High-grade prostatic intraepithelial neoplasia in dogs.

The dog is the only nonhuman species in which high-grade intraepithelial neoplasia (HGPIN) and invasive carcinoma spontaneously occur. Our work was the first to describe HGPIN in the dog prostate. Canine HGPIN bears remarkable morphologic similarity to its human counterpart. There is also striking similarity between canine and human HGPIN with respect to basal layer disruption, proliferative index, and microvessel density. For each of these parameters, HGPIN is intermediate between benign epithelium and invasive carcinoma, strengthening the hypothesis that HGPIN is an intermediate step on the road to prostate cancer. In another study, we showed that HGPIN is present in the majority (55%) of elderly sexually intact pet dogs without clinical evidence of prostate cancer. These data suggest that the early events of prostate carcinogenesis may occur with high frequency within the prostates of pet dogs sharing the same environment as humans. We are currently conducting a large-scale autopsy-epidemiological study to further characterize the epidemiology of HGPIN and invasive carcinoma in pet dogs. We are also testing the potential utility of pet dogs for the rapid, cost-effective in vivo screening of chemopreventive agents by using the prevalence and extent of HGPIN in the dog prostate as a surrogate endpoint biomarker.