A study of cytokeratin 20 immunostaining in the urothelium of neuropathic bladder of patients with spinal cord injury

Abstract

BackgroundNormal urothelium is characterised by terminally differentiated superficial cells, which express cytokeratin 20 in the cytoplasm. In contrast, cultured human stratified urothelium, which does not undergo complete terminal differentiation of its superficial cells, does not express cytokeratin 20. If spinal cord injury (SCI) affects urothelial differentiation or induces squamous or other metaplastic change undetected by histological analysis, the superficial urothelial cells of the neuropathic bladder might be expected to show absence of immunostaining for cytokeratin 20.Patients and MethodsWe studied immunostaining for cytokeratin 20 in bladder biopsies taken from 63 consecutive SCI patients. Immunostaining was performed on paraffin-embedded tissue using a mouse monoclonal antibody (clone: Ks20.8).ResultsOf 63 biopsies, the epithelium was scarce in two. Eight biopsies showed squamous metaplasia and immunostaining for cytokeratin 20 was absent in all the eight biopsies. Of the remaining 53 cases, in which the umbrella cell layer of the urothelium was intact, immunostaining for cytokeratin 20 was seen only in ten biopsies.ConclusionSuperficial cells in the transitional epithelium showed immunostaining for cytokeratin 20 in 10 of 53 bladder biopsies taken from SCI patients. The reasons for this could be either that there is an underlying metaplasia or that changes in the neuropathic bladder affect urothelial differentiation. Taken with evidence from other systems, such as loss of cytokeratin 20 expression from static organ cultures of urothelial tissue, this might suggest that other factors, such as impairment of voluntary voiding in SCI patients, could affect expression of markers such as cytokeratin 20.

Urothelial Signaling

“…These alterations are prevented by pretreatment with ganglionic blockers, suggesting that bladder nerves play a role in acute response of urothelial cells to injury. In SCI patients there is evidence that impairment of voluntary voiding may correlate with increased metaplasia and/or diminished urothelial differentiation (286). Changes in epithelial proliferation or metaplasia may be due to altered expression of molecules such as parathyroid hormone-related protein (PTHrP), which is a secretory factor that can act in autocrine, paracrine, as well as intracrine manners in a number of tissues.…”

Optimization of the current self-assembled urinary bladder model: Organ-specific stroma and smooth muscle inclusion

“…CK14 does not stain on normal urothelium and signifies vulnerability of the bladder to future disease. [29][30][31] It is detected in pathologic bladders, denoting squamoid phenotype change of urothelium. It is observed before morphologic squamoid differentiation and is considered a reactive response to urothelial stress or injury.…”

Human Urothelial Cells Isolation, In Vitro Expansion and Characterization for Evaluating Bio-Engineering Potentials

“…CK7, CK18, and CK19 are the markers expressed throughout all layers in normal urothelium [7] . Available literature towards urothelium basal layer characterization have shown that urothelium cells were expressing phenotypic marker CK5 and CK17, but they did not express phenotypic marker CK20, which is generally associated with differentiated superficial cells [7,8,9] . The urothelium or transitional epithelium of the urinary tract shows alterations in the expression and configuration of cytokeratin isotypes associated with stratification and differentiation.…”

“…However, such adult stem cells in human urothelium, displaying clonogenicity, self-renewal, and differentiation potential have not been elaborately described. Urothelial stem cells capable of regenerative potential were isolated from mice tissue, which was found to express sonic hedgehog and p63 proteins in the basal cell layers of the bladder urothelium [7,8] . A recent report has also shown p63 expression in porcine urothelial and human urothelial cells [9] .…”