Immunohistochemical expression of p63, Ki67 and β‐catenin in canine transitional cell carcinoma and polypoid cystitis of the urinary bladder

Abstract

Transitional cell carcinoma (TCC) is a urinary bladder tumour associated with high mortality in dogs. In this study, we investigated the feasibility of using p63, Ki67 or β-catenin as a clinical marker for predicting biological behaviour and prognosis in canine TCC. Expression levels of these proteins in TCC (n = 25), polypoid cystitis (n = 5) and normal urinary bladder (n = 5) were scored after immunohistochemical staining. The staining scores for p63 (P < 0.01) and β-catenin (P < 0.05) in TCC were significantly lower than those in normal urinary bladder and polypoid cystitis. In contrast, Ki67 (P < 0.01) staining scores in TCC were significantly higher than those in normal urinary bladder and polypoid cystitis. In TCC, low p63 expression was significantly related to the presence of vessel invasion (P < 0.05) and metastasis (P < 0.01) as well as short survival time (P < 0.05). These findings show that p63 could be a reliable marker for predicting prognosis in canine TCC.

Naturally-Occurring Canine Invasive Urothelial Carcinoma: A Model for Emerging Therapies

“…Loss of p53 expression has been observed in human invasive InvUC and has been associated with lymph node metastasis, advanced tumor-node-metastasis stage, and decreased survival times [ 35, 36 ]. Comparable to reports in humans, p63 expression, a homologue of p53, has been reported to be significantly lower in dogs with InvUC, compared to dogs with polypoid cystitis and normal urothelium [ 37 ]. Expression of p53, the p53 inducible gene 14-3-3 σ protein, and vimentin have been documented in a portion of canine InvUC in vivo and in vitro .…”

Comparative Cancer Cell Signaling in Muscle-Invasive Urothelial Carcinoma of the Bladder in Dogs and Humans

“…Accordingly, strong membranous β-catenin staining in IHC was observed in normal canine urinary bladder (n = 5) and cystitis (n = 5) specimens, whereas staining intensity in localized canine UC tumors (n = 25) was significantly lower (p < 0.05) [48]. Moderate vimentin protein expression has been reported in canine UC cell lines [164], and vimentin was expressed in the invasive front of canine UC tumors (n = 19).…”

“…Lower expression of p63 in IHC was significantly associated with vascular infiltration (p < 0.05), presence of metastasis (p < 0.01) and shorter dog survival (p < 0.05) when compared to dogs with higher p63 expression. It was concluded that p63 could serve as biomarker for the prognosis of canine UC (Table 2) [48]. In 2018, pathway analysis by RNA-seq identified the p53 pathway to be significantly downregulated (bias-corrected z score = −2.977) in canine MIUC tumors versus normal bladder tissue [49].…”

Molecular Markers in Urinary Bladder Cancer: Applications for Diagnosis, Prognosis and Therapy

“…The potential usefulness of proteins p63, Ki67 and β-catenin as clinical markers for predicting biological behaviour and prognosis was investigated in canine TCC [ 96 ]. It is thought that p63 plays an important role in cellular development and differentiation of stratified epithelia in skin, prostate gland, mammary gland and urinary bladder [ 96 , 97 , 98 , 99 ]. In humans, loss of p63 expression has been associated with tumourigenesis and malignancy [ 100 , 101 ].…”

“…In humans, loss of p63 expression has been associated with tumourigenesis and malignancy [ 100 , 101 ]. Ki67 is a nuclear protein expressed by proliferating cells, while membranous β-catenin is involved in cellular adherence, and a reduced expression of this protein has been linked to progression and poor prognosis in human urothelial carcinoma [ 96 ].…”