Waters D J
Cancer Biology Laboratory, School of Veterinary Medicine, Purdue University, West Lafayette, Ind. 47907, USA.
Eur Urol. 1999;35(5-6):456-8. doi: 10.1159/000019878.
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.
狗是唯一会自发出现高级别上皮内瘤变（HGPIN）和浸润性癌的非人类物种。我们的研究首次描述了犬前列腺中的HGPIN。犬HGPIN在形态学上与其人类对应物具有显著相似性。在基底层破坏、增殖指数和微血管密度方面，犬和人类的HGPIN也有惊人的相似之处。对于这些参数中的每一个，HGPIN都介于良性上皮和浸润性癌之间，这强化了HGPIN是前列腺癌发展道路上的一个中间步骤的假设。在另一项研究中，我们发现大多数（55%）性成熟的老年宠物狗存在HGPIN，但无前列腺癌的临床证据。这些数据表明，在与人类共享相同环境的宠物狗前列腺中，前列腺癌发生的早期事件可能频繁发生。我们目前正在进行一项大规模的尸检流行病学研究，以进一步描述宠物狗中HGPIN和浸润性癌的流行病学特征。我们还在测试宠物狗作为化学预防剂快速、经济高效的体内筛选工具的潜在效用，将犬前列腺中HGPIN的患病率和程度作为替代终点生物标志物。
