Pathology of canine bladder and urethral cancer and correlation with tumour progression and survival

doi:10.1016/S0021-9975(05)80027-1

Journal of Comparative Pathology

Volume 113, Issue 2, August 1995, Pages 113-130

https://doi.org/10.1016/S0021-9975(05)80027-1 Get rights and content

Summary

Biopsy and necropsy specimens, comprising 107 primary carcinomas and three mesenchymal tumours, were reviewed from 110 dogs with cancer of the bladder, urethra, or both. Histological classifications developed for the assessment of human bladder cancer were found to be readily applicable to the dog. These classifications are based on histological features, including the pattern of growth, the cell type, the grade of transitional tumour and the depth of invasion of the bladder wall.

Features associated with localized disease in canine transitional cell carcinoma included papillary architecture, “in-situ” tumour, low tumour grade and a strong peritumoral lymphoid cell reaction. Features of tumours with metastasis included infiltrating and non-papillary architecture, increasing tumour grade, depth of invasion, vascular invasion and presence of peri-tumoral fibrosing reaction. Wide variability was found within single tissue samples, indicating that multiple sample sites are necessary for the adequate characterization of a given lesion.

Statistically significant correlations were found between: tumour grade and depth of invasion (P<0·0001); tumour grade and presence of metastases (P<0·029); and peritumoral desmoplasia and metastases (P<0·029).

It was concluded that canine bladder cancer could be classified for the purpose of clinical management with a modified World Health Organization system as developed for human tumours.

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Establishment of an experimental model of normal dog bladder organoid using a three-dimensional culture method
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Citation Excerpt :
In dogs, BC occurs at a similar rate with humans (1–2% of all canine tumors) [5]. However, the majority of dog BC is moderate to high-grade MIBC (≥ 90% of the cases) [6–9], less responsive to chemotherapy [10], and more often in females than males [5,11]. It also has a poor prognosis due to its frequent occurrence in the trigone of the bladder and the difficulty of complete surgical resection [8].
Dog bladder cancer (BC) is mostly muscle-invasive (MI) with poor prognosis, and its pathogenesis is close to human MIBC. Three-dimensional (3D) organoid culture ensures novel knowledge on cancer diseases including BC. Recently, we have established dog BC organoids (BCO) using their urine samples. BCO recapitulated the epithelial structures, characteristics, and drug sensitivity of BC-diseased dogs. However, organoids from dog normal bladder epithelium are not established yet. Therefore, the present study aimed to establish dog normal bladder organoids (NBO) for further understanding the pathogenesis of dog BC and human MIBC. The established NBO underwent various analyzes including cell marker expressions, histopathological structures, cancer-related gene expression patterns, and drug sensitivity. NBO could be produced non-invasively with a continuous culturing and recapitulated the structures and characteristics of the dog's normal bladder mucosal tissues. Different drug sensitivities were observed in each NBO. The analysis of RNA sequencing revealed that several novel genes were changed in NBO compared with BCO. NBO showed a higher expression of p53 and E-cadherin, but a lower expression of MDM2 and Twist1 compared with BCO. These results suggest that NBO could be a promising experimental 3D model for studying the developmental mechanisms of dog BC and human MIBC.
Antitumor activity of an oncolytic measles virus against canine urinary bladder transitional cell carcinoma cells
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The prognosis of canine transitional cell carcinoma (TCC) of urinary bladder is generally poor because it is difficult to diagnose at early stages and conventional therapies, such as surgical resection and/or chemotherapy, are often not curative treatments. Based on our previous report that recombinant measles virus (rMV-SLAMblind) therapy could be a new treatment for canine mammary tumor, the applicability of rMV-SLAMblind in canine urinary bladder TCC was examined in this study. A canine TCC cell line was established from a TCC patient dog by transplanting a piece of the tumor mass into an immunodeficient mouse and then isolating the primary TCC cells from the grown tumor mass. The primary cultured cells, named TCC-NU1, express nectin-4, a receptor for rMV-SLAMblind infection. The rMV-SLAMblind infected TCC-NU1 cells, and dose-dependently showed cell cytotoxicity. Moreover, intratumoral administration of rMV-SLAMblind in a xenograft model bearing TCC-NU1 cells significantly suppressed the tumor growth reducing the endpoint mass of tumors in treated mice compared to control mice. These results suggest that virotherapy with rMV-SLAMblind be a new candidate therapy for canine TCC.
Lipoxygenase-5 Expression in Canine Urinary Bladder: Normal Urothelium, Cystitis and Transitional Cell Carcinoma
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Citation Excerpt :
Tumours of the urinary bladder account for 2% of all malignant tumours in dogs, with almost 90% being malignant and of epithelial origin (Knapp et al., 2014; Meuten and Meuten, 2017). Transitional cell carcinoma (TCC), also referred to as urothelial carcinoma, is known to be the most common (75–90%) of these neoplasms with the majority of TCCs (>90% of cases) having an intermediate or high histological grade and showing an invasive behaviour (Valli et al., 1995; Anderson et al., 2002; Patrick et al., 2006). The treatment of canine TCC can include surgery, radiation therapy and/or chemotherapy; however, the latter is used most commonly (Knapp et al., 2014).
Transitional cell carcinoma (TCC) is the most common canine urinary tract tumour and mimics human invasive TCC. Human TCCs overexpress lipoxygenase (LOX)-5 and the use of target inhibitors has proven effective in inhibiting neoplastic growth. In this study, we investigated the immunohistochemical expression of LOX-5 in normal canine urinary bladder, cystitis and TCC. The comparative expression of LOX-5, cyclo-oxygenase (COX)-1 and COX-2 among the three tissue groups was also examined. Biopsy samples from cases of cystitis and TCC were reviewed from 2012 to 2016; samples of histologically normal bladder were used as controls. Dogs were excluded if they had received glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs) and/or chemotherapy prior to tissue collection. LOX-5 was expressed in 95% of TCCs, 23% of cases of cystitis and 10% of controls. LOX-5 and COX-2 immunohistochemistry scores were significantly (P <0.01) higher in TCCs versus cystitis and normal bladders. Results of this study support the rationale for further investigation of the use of NSAIDs with dual anti COX-2 and LOX-5 effect for the treatment of canine TCC.
A Fibromyxoid Stromal Response is Associated with Muscle Invasion in Canine Urothelial Carcinoma
2019, Journal of Comparative Pathology
Canine urothelial carcinoma (UC) is the most common type of cancer of the lower urinary tract and tends to affect elderly neutered female dogs, with a high predisposition for Scottish terriers. Tumour stroma, inflammation and necrosis are poorly characterized in canine UC and their role as prognostic factors is unknown. The aims of this study were to (1) assess histologically 381 canine UCs, with emphasis on myxoid tumour stroma, inflammation and necrosis and (2) assess possible associations between these features and the available epidemiological data as well as bladder wall muscle invasion. In 103 of 381 (27%) cases, the stroma was mixed collagenous and myxoid (fibromyxoid), which was strongly associated with invasive growth of muscle (P <0.0001). Peritumoural and intratumoural inflammation was present in 308 of 345 (89%) and 287 of 381 (75%) cases, respectively, and was mostly mild and lymphoplasmacytic. One hundred and fifteen of the 381 (30%) cases showed a variable eosinophilic inflammation and 58 of 381 (15%) presented with formations of one or several lymphoid follicles. Twenty-four percent (91 of 381) of cases had tumour necrosis, which was typically mild. In 83 of 91 (91%) cases, the necrosis was comedo-like. Moderate to severe tumour necrosis was associated with the presence of moderate to predominant fibromyxoid tumour stroma (P <0.02). The results of this study indicate that fibromyxoid stroma is common in canine UC and is a strong indicator for invasive growth of muscle, which is consistent with a poor prognosis. Based on histomorphology, tumour necrosis in canine UC is best described as comedonecrosis.
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2024, Veterinary Surgery
Reason for euthanasia in dogs with urothelial carcinoma treated with chemotherapy or radiation therapy or both: A retrospective observational study
2024, Journal of Veterinary Internal Medicine

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Journal of Comparative Pathology

Summary

References (25)

Saccharin: a toxicological and historical perspective

Toxicology

Bracken carcinogenicity

Research in Veterinary Science

Immunoresponse of tissue infiltrating lymphocytes in bladder tumors

Journal of Urology

Ultrastructure of canine urinary bladder carcinoma

Veterinary Pathology

A review of the environmental and mammalian toxicology of nitrilotriacetic acid

CRC Critical Reviews in Toxicology

Wound healing in nude mice: a study on the regulatory role of lymphocytes in fibroplasia

Surgery

Malignancy grading of epithelial bladder tumours

Scandinavian Journal of Urology and Nephrology

Cyclophosphamide-induced cystitis in the dog and cat

Journal of the American Veterinary Medical Association

Avoidable risks of cancer in the U.S.

Journal of the National Cancer Institute

Transitional cell carcinoma in situ

Canine bladder cancer: epidemiologic features

American Journal of Epidemiology

Bladder cancer in pet dogs: a sentinel for environmental cancer?

American Journal of Epidemiology

Cited by (102)

Establishment of an experimental model of normal dog bladder organoid using a three-dimensional culture method

Antitumor activity of an oncolytic measles virus against canine urinary bladder transitional cell carcinoma cells

Lipoxygenase-5 Expression in Canine Urinary Bladder: Normal Urothelium, Cystitis and Transitional Cell Carcinoma

A Fibromyxoid Stromal Response is Associated with Muscle Invasion in Canine Urothelial Carcinoma

Feasibility of laparoscopic stapled partial cystectomy in canine cadavers

Reason for euthanasia in dogs with urothelial carcinoma treated with chemotherapy or radiation therapy or both: A retrospective observational study