Comparative histologic survey and transcriptomic investigation into canine prostate carcinoma

Dogs share features in prostate gland anatomy, physiology, and pathology with men. However, human and canine prostate carcinoma (PC) have histologic and molecular differences. Particularly, the histogenesis of canine PC (cPC) is unclear. This study investigated the origin of cPC using histopathology and transcriptomics with comparison to men. Prostate glands retrospectively and prospectively collected from 445 dogs (approximately 95 % autopsy samples) were surveyed for early carcinomas and preneoplastic lesions, particularly high-grade prostatic intraepithelial neoplasia (HGPIN) due to its role in the pathogenesis of PC in men. Lineage gene signatures defining prostate luminal epithelium and urothelium were identified for inter- and intraspecies RNA-sequencing comparisons, including between cPC and canine urinary bladder urothelial carcinoma (UC). Postmortem prostate lesion frequencies were similar to previously reported canine studies. Intraductal/intra-acinar growth (31/35; 88.6 %) was common in representative samples of cPC. Prostate epithelial changes consistent with HGPIN in men were not observed. Proliferative lesions and early carcinomas were rare (7/445; 1.6 %). Patterns in prostate and urothelium marker gene expression signatures differed between human and canine PC. Compared to non-neoplastic prostate gland, cPC had significantly decreased prostate-specific and increased urothelium gene signatures. The results suggest many cases diagnosed as cPC are UC or have urothelial differentiation and thus differ from PC in men, with important implications for canine tumor classification and translational studies.