Histological and immunohistochemical investigation of canine prostate carcinoma with identification of common intraductal carcinoma component

Abstract

A limited number of species, including men and dogs, spontaneously develop prostate cancer (PC). The histological and molecular relevance of canine PC as a model for the disease in men remains controversial. To address this challenge, this study aimed to assess the histomorphology and expression of basal cell, urothelial and neuroendocrine markers [p63, high molecular weight cytokeratin (HMWCK), Uroplakin 3 (UPIII), neuron-specific enolase (NSE)] in canine PC (n = 41). Based on histomorphology, 10/41 (24%), 21/41 (51%) and 9/41 (22%) were classified as adenocarcinoma (AC), urothelial carcinoma (UC), and mixed carcinoma, respectively.Tumour inflammation was common, frequently severe [20/41 (49%)], and associated with neutering (p < .02) and urothelial differentiation (p < .02). Most (36/40, 90%) cancers contained only rare cells with basal cell marker expression or were negative.The expression of UPIII was absent or weak in the majority (33/38, 87%) of tumours, with moderate to strong staining in the remaining cases. NSE expression in PC was rare and limited to 2/14 (14%) cases. Tumour extension into benign ducts and glands was a common finding with presence in 17/39 (44%) of carcinomas with and without urothelial differentiation. In conclusion, we confirm that canine PC is characterized by absent or weak expression of basal cell and urothelial markers. Although rare, NSE expression, potentially indicating neuroendocrine differentiation, is reported for the first time in canine PCa. Intraductal carcinoma of the prostate with concurrent invasive PCa (IDCP-inv) is a frequent, not previously described, finding in dogs with PC.

Diseases of the Canine Prostate Gland

“…Recent studies focus on the detection and development of biomarkers for canine prostate cancer [126,127]. Markers are not easy to find in case of canine prostate cancer since the tumor growth is aggressive and the pattern variable, the basal cell layer is discontinuous and markers are frequently absent.…”

“…Markers are not easy to find in case of canine prostate cancer since the tumor growth is aggressive and the pattern variable, the basal cell layer is discontinuous and markers are frequently absent. A combination of markers might DOI: http://dx.doi.org/10.5772/intechopen.105835 increase the diagnostic accuracy [127]. For a precise immunohistochemical analysis, different markers are necessary to differentiate between urethral, glandular, or ductal origin of the tumor, which is possible in human medicine but not sufficiently investigated in the dog.…”

Comparative Pathobiology of Canine and Human Prostate Cancer: State of the Art and Future Directions

“…In addition to basal and luminal markers, canine PC can also be derived from prostatic ducts and not only from acinar cells, considering that a significant portion of PC samples express uroplakin III (UPIII), a transmembrane protein expressed by apical urothelial cells [ 57 , 73 , 74 ]. Together with CK7, UPIII was considered a marker of significant specificity for urothelial differentiation, that is, for the diagnosis of canine urothelial carcinoma of the prostate since the expression of p63 and high molecular weight cytokeratin is scarce or absent in these cases [ 57 , 73 , 74 ]. However, immunostaining for UPIII may be mild or negative in some tumors with a mixed histological pattern [ 74 ].…”

“…Together with CK7, UPIII was considered a marker of significant specificity for urothelial differentiation, that is, for the diagnosis of canine urothelial carcinoma of the prostate since the expression of p63 and high molecular weight cytokeratin is scarce or absent in these cases [ 57 , 73 , 74 ]. However, immunostaining for UPIII may be mild or negative in some tumors with a mixed histological pattern [ 74 ].…”

“…In this sense, the presence of stromal inflammatory cells in benign and malignant human prostate tissue is a common finding on histopathological examination, which also occurs in the gland of the canine species [ 190 ]. Stromal lymphoplasmacytic infiltrate is frequent in canine PC and appears more pronounced in tumors with urothelial differentiation and castrated dogs [ 74 ]. Furthermore, the presence and constant stimulation of inflammation trigger oxidative stress and genomic damage, playing an important role not only in carcinogenesis and tumor progression [ 190 ] but in the survival of the affected patient, depending on the cell type involved [ 191 , 192 ].…”