Differences in Expression of Uroplakin III, Cytokeratin 7, and Cyclooxygenase-2 in Canine Proliferative Urothelial Lesions of the Urinary Bladder

Abstract

The expression of immunohistochemical markers that have been used in diagnosis and/or prognostication of urothelial tumors in humans (uroplakin III [UPIII], cytokeratin 7 [CK7], cyclooxygenase-2 [COX-2], and activated caspase 3) was evaluated in a series of 99 canine proliferative urothelial lesions of the urinary bladder and compared to the lesion classification and grade as defined by the World Health Organization / International Society of Urologic Pathology consensus system. There were significant associations between tumor classification and overall UPIII pattern (P ¼ 1.49 Â 10 -18 ), loss of UPIII (P ¼ 1.27 Â 10 -4 ), overall CK7 pattern (P ¼ 4.34 Â 10 -18 ), and COX-2 pattern (P ¼ 8.12 Â 10 -25). In addition, there were significant associations between depth of neoplastic cell infiltration into the urinary bladder wall and overall UPIII pattern (P ¼ 1.54 Â 10 ). There were no significant associations between tumor classification or infiltration and caspase 3 expression pattern.Keywords dog, urinary bladder, oncology, immunohistochemistry, transitional cell carcinoma, uroplakin III, neoplasia, cytokeratin Proliferative lesions of the urothelium of the canine urinary bladder range from benign polyps and papillomas to carcinomas with varying metastatic potential. Also, inflammatory conditions such as polypoid cystitis can form tumor-like masses within the urinary bladder that can be confused with urothelial neoplasms. Classification of urothelial proliferative lesions and histologic grading of urothelial carcinomas is key to accurate prognostication and treatment selection. A classification and grading scheme based on the 1986 World Health Organization (WHO) classification scheme for human urinary bladder and urethral cancer was proposed in 1995 for use in evaluating urothelial neoplasms in dogs based on pattern of growth, nuclear atypia, and degree of infiltration into the urinary bladder wall. 50 In the initial description of this system's use in dogs, significant correlations were found between tumor grade and depth of infiltration, the presence of metastases, and survival time. However, a subsequent smaller study failed to find a significant correlation between grade and prognosis. 41 To our knowledge, this scheme is not widely used in dogs and has been replaced in human medicine by more modern classification schemes. There remains a need for a clear, reproducible, and well-accepted classification and grading scheme for urothelial proliferative lesions in dogs.Currently, the most widely accepted scheme for classification and grading of proliferative urothelial lesions in humans is the WHO / International Society of Urologic Pathology (ISUP) consensus classification system, published in 1998 and updated in 2004. 6,7 In multiple studies, the WHO/ISUP consensus classification system has been demonstrated to be significantly associated with clinical outcome. 2,[32][33][34]37,42,43,51,59 It has long been known that canine urothelial neoplasms are similar to urothelial neoplasms in humans in terms o...

Characterization of six canine prostate adenocarcinoma and three transitional cell carcinoma cell lines derived from primary tumor tissues as well as metastasis

“…UPIII protein, usually expressed by urothelial cells [94], was not detected in any of the samples, which is contrary to other studies with large numbers of canine non-neoplastic prostate and neoplastic bladder samples [59,94]. This may be caused by areal UPIII expression losses in high grade TCCs [96]. None of the analyzed immunohistochemical markers is appropriate to distinguish between PAC and TCC in this study.…”

Assessment of HER2 Expression in Canine Urothelial Carcinoma of the Urinary Bladder

“…All UC samples were evaluated in full thickness, and histological gradings of grade 1 (low grade), grade 2 (intermediate grade), and grade 3 (high grade) were assigned according to previous reports on canine proliferative urothelial lesions. 25,31…”

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“…Previous established criteria were used to classify lesions as adenomas or carcinomas [ 36 ]. In addition, immunohistochemical (IHC) labeling for Melan-A and inhibin (Dako, Carpinteria, CA, USA) was performed on 5 μm serial sections of two of the three submitted adrenal gland specimens, and immunolabeling for caspase-3 (RDI/Fitzgerald, Acton, MA, USA), was performed on two of the three adrenal gland specimens [ 37 , 38 ]. Immunolabeling for inhibin was performed on a Leica Bond-Max autostainer (Leica Microsystems, Buffalo Grove, IL, USA).…”