BACKGROUND. In this study we try to identify the origin of canine prostate cancer (cPC) by classifying the tumors histological subtypes and relate these subtypes to their combined expressional characteristics of several tissue specific and differentiation markers. METHODS. cPCs were examined histomorphologically and by immunohistochemical detection of the cytokeratin markers CK14, HMWCK, CK5, CK18, and CK7, and of the markers UPIII, PSA and PSMA. RESULTS. Histopathologically, six growth patterns could be differentiated. The most frequent patterns were solid, cribriform and micropapillary growth patterns, while sarcomatoid, small acinar/ductal, and tubulo-papillary growth patterns were less frequent present. Solid growth patterns were significantly (P ¼ 0.027) more often seen in castrated dogs. Immunohistochemically, about half of the cPC cases showed expression of PSA (8/20) and PSMA (10/20); 85% and 60% of the cPC expressed UPIII (17/20) and CK7 (12/20), while 13 and 12 cPC expressed CK5 and CK14, respectively; all cPC expressed CK18. CK14 was significantly more often and UPIII less frequent expressed in the solid growth patterns than in the micropapillary and cribriform patterns, respectively. CONCLUSIONS. Canine prostate cancer appear to be more aggressive and of a less differentiated type than most common human prostate cancers. Comparing the expression patterns of the markers in cPC to those in normal canine prostate tissue, cPC most likely originates from the collecting ducts rather than from the peripheral acini. Given also the fact that canine prostate cancer is unresponsive to androgen withdrawal therapy, canine prostate cancer mostly resembles human, androgen refractory, poorly differentiated prostate cancer.

Background Prostate diseases in the dog are generally regarded as representative for their human counterparts. We characterized the normal canine prostate in comparison to the normal human prostate. Methods Prostates of dogs were examined histomorphologically and by immunohistochemical detection of the markers CK14, HMWCK, CK5, CK18, CK7, UPIII, PSA, and PSMA. Results Histomorphologically, the canine prostate lacks the human zonal differentiation, has much more prominent acini, while comprising less stromal tissue. In general, the canine prostate epithelium displayed a highly differentiated character, with no cells expressing CK14, minimal amounts of cells expressing HMWCK/CK5 and the vast majority of cells expressing CK18 and PSA. After castration, the prostate epithelium regressed, and the remaining tubules were largely populated by cells showing a ductal phenotype (HMWCK+/CK5+/CK18+/CK7+). Conclusions The human and canine prostate are histologically differently organized. The general scheme of cellular differentiation of the prostate epithelium may however be applicable to both species. Prostate 68: 498–507, 2008. © 2008 Wiley‐Liss, Inc.

Mammary cancer is the most common type of cancer in female dogs with a lifetime risk of over 24% when dogs are not spayed. The elucidation of the complete canine genome opens new areas for development of cancer therapies. These should be tested first by in vitro models such as cell lines. However, to date, no canine mammary cell lines have been characterized by expression profiling. In this study, canine mammary tumour cell lines with histologically distinct primary tumours of origin were characterized using a newly developed canine cDNA microarray. Comparisons of gene expression profiles showed enrichment for distinct biological pathways and were related to biological properties of the cell lines such as growth rate and in vitro tumourigenicity. Additionally, gene expression profiles of cell lines also showed correspondence to their tumour of origin. Major differences were found in Wnt, cell cycle, cytokine/Rho-GTPase, alternative complement and integrin signalling pathways. Because these pathways show an overlap at the molecular level with those found in human breast cancer, the expression profiling of spontaneous canine mammary cancer may also function as a biological sieve to identify conserved gene expression or pathway profiles of evolutionary significance that are involved in tumourigenesis. These results are the basis for further characterization of canine mammary carcinomas and development of new therapies directed towards specific pathways. In addition these cell lines can be used to further investigate identified deregulated pathways and characterize until now unannotated genes.

Background: Relatively shorter lengths of the polymorphic polyglutamine repeat-1 of the androgen receptor (AR) have been associated with an increased risk of prostate cancer (PC) in humans. In the dog, there are 2 polymorphic CAG repeat (CAGr) regions.Objective: To investigate the relationship of CAGr length of the canine AR-gene and the development of PC. Animals: Thirty-two dogs with PC and 172 control dogs were used. Methods: DNA was extracted from blood. Both CAG repeats were amplified by polymerase chain reaction (PCR) and PCR products were sequenced.Results: In dogs with PC, CAG-1 repeat length was shorter (P 5 .001) by an increased proportion of 10 repeats (P 5 .011) and no 12 repeats (P 5 .0017) than in the control dogs. No significant changes were found in CAG-3 length distribution. CAG-1 and CAG-3 polymorphisms proved not to be in linkage disequilibrium.Breed difference in allelic distribution was found in the control group. Of the prostate-disease sensitive breeds, a high percentage (64.5%) of the shortest haplotype 10/11 was found in the Doberman, whereas Beagles and German Pointers had higher haplotype 12/11 (47.1 and 50%). Bernese Mountain dogs and Bouvier dogs both shared a high percentage of 11 CAG-1 repeats and 13 CAG-3 repeats. Differences in (combined) allelic distributions among breeds were not significant.Conclusions and Clinical Importance: In this preliminary study, short CAG-1 repeats in the AR-gene were associated with an increased risk of developing canine PC. Although breed-specific differences in allelic distribution of CAG-1 and CAG-3 repeats were found, these could not be related to PC risk.

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