Cytokeratin expression patterns in normal and malignant urothelium: a review of the biological and diagnostic implications

ICRF Cancer Medicine Research Unit, Research School of Medicine, St James's University Hospital, Leeds, UK.
Histology and histopathology (Impact Factor: 2.24). 05/1999; 14(2):657-64.
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ABSTRACT The cytokeratins are the intermediate filament proteins characteristic of epithelial cells. In human cells, some 20 different cytokeratin isotypes have been identified. Epithelial cells express between two and ten cytokeratin isotypes and the consequent profile which reflects both epithelial type and differentiation status may be useful in tumour diagnosis. The transitional epithelium or urothelium of the urinary tract shows alterations in the expression and configuration of cytokeratin isotypes related to stratification and differentiation. In transitional cell carcinoma, changes in cytokeratin profile may provide information of potential diagnostic and prognostic significance. The intensification of immunolabelling with some CK8 and CK18 antibodies may underly an active role in tumour invasion and foci of CK17-positive cells may represent proliferating populations. Loss of CK13 is a marker of grade and stage and de novo expression of CK14 is indicative of squamous differentiation and an unfavourable prognosis. However, perhaps the most important recent finding is the demonstration that a normal CK20 expression pattern is predictive of tumour non-recurrence and can be used to make an objective differential diagnosis between transitional cell papilloma and carcinoma. This review will consider cytokeratin expression in urothelium and discuss the application of cytokeratin typing to the diagnosis and prognosis of patients with TCC.

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    • "Both urothelial cells and detrusor muscle cells are relatively straightforward to isolate and propagate in culture (Birder et al., 2003; Sun and Chai, 2002). AE1/AE3 is a marker for urothelial cells known to react against an antigenic determinant present on the majority of the subfamily A and B cytokeratins (Eichner et al., 1984; Sun et al., 1984), and has previously been employed in studies of the urothelium (Trifillis et al., 1995; Southgate et al., 1999). Smooth muscle actin (α-SMA) is a contractile protein present in both smooth muscle (Roholl et al., 1990) and myofibroblasts (Drake et al., 2006; Sadananda et al., 2008; Iwanaga et al., 2010; McCloskey, 2010). "
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    ABSTRACT: ATP is released from the bladder mucosa in response to stretch, but the cell types responsible are unclear. Our aim was to isolate and characterize individual populations of urothelial, myofibroblast, and detrusor muscle cells in culture, and to examine agonist-stimulated ATP release. Using female pig bladders, urothelial cells were isolated from bladder mucosa following trypsin-digestion of the luminal surface. The underlying myofibroblast layer was dissected, minced, digested, and cultured until confluent (10-14 days). A similar protocol was used for muscle cells. Cultures were used for immunocytochemical staining and/or ATP release investigations. In urothelial cultures, immunoreactivity was present for the cytokeratin marker AE1/AE3 but not the contractile protein α-smooth muscle actin (α-SMA) or the cytoskeletal filament vimentin. Neither myofibroblast nor muscle cell cultures stained for AE1/AE3. Myofibroblast cultures partially stained for α-SMA, whereas muscle cultures were 100% stained. Both myofibroblast and muscle stained for vimentin, however, they were morphologically distinct. Ultrastructural studies verified that the suburothelial layer of pig bladder contained abundant myofibroblasts, characterized by high densities of rough endoplasmic reticulum. Baseline ATP release was higher in urothelial and myofibroblast cultures, compared with muscle. ATP release was significantly stimulated by stretch in all three cell populations. Only urothelial cells released ATP in response to acid, and only muscle cells were stimulated by capsaicin. Tachykinins had no effect on ATP release. In conclusion, we have established a method for culture of three cell populations from porcine bladder, a well-known human bladder model, and shown that these are distinct morphologically, immunologically, and pharmacologically.
    Frontiers in Pharmacology 06/2011; 2(article 27):27. DOI:10.3389/fphar.2011.00027 · 3.80 Impact Factor
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    • "Cells of the intermediate and luminal layers express keratins 7, 8, 18, 19; cytokeratin 20 is only revealed in the outer luminal layer of the urothelium (Southgate et al., 1999). The distinct feature of umbrellaalike cells is the asymmetric plasma memm brane with plagues that contain tissue specific proo teins, i.e., uroplakins, which are responsible for the urothelium's capacity to control permeability (Wu et al., 1994). "
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    ABSTRACT: The autoplastic surgery by intestine tissue has been used for reconstructive therapy of the urinary tract since the middle of the last century; however, cell mechanisms of the urothelium engraftment are still obscure. Intestine stem cells possess plasticity and presumably enable after the autoplastic surgery to transdifferentiate into mature cells of urinary tract. Using the preliminary developed in vivo model for evaluation of somatic cells transdifferentiation into urothelium, we have found that the epithelial intestine cells producing Gfp transdifferentiate into the cryoinjured bladder urothelium of the syngenetic C57BL mice. Gfp was detected in the bladder tissue of mice-recipients using reverted polymerase chain reaction, primary fluorescence and immunofluorescence, while colocalization of the Gfp and Her-4 revealing similar to urothelium staining pattern was demonstrated in a few urothelium cells by double immunohistochemical staining of the bladder tissue with specific antibodies. The results obtained suggest that epithelial intestine cells enable to transdifferentiate into bladder urothelium, however the transdifferentiation level is low and presumably can not provide full functional urothelium engraftment in the case of autoplastic bladder surgery by intestine tissue.
    Tsitologiia 01/2011; 53(4):332-40.
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    • "In humans 20 different cytokeratin isotypes have been identified. Cytokeratins 8, 18, 19, and 20 have been associated with bladder cancer [40]. The Urinary Bladder Cancer (UBC) test detects cytokeratin 8 and 18 fragments in urine. "
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    ABSTRACT: Many markers for the detection of bladder cancers have been tested. Almost all urinary markers reported are better than cytology with regard to sensitivity, but they score lower in specificity. The purpose of this review is to highlight the most important urinary biomarkers studied and reported recently. Literature on bladder cancer markers has been reviewed regularly in the last few years. In the current review we have tried to summarise the most recent literature of urinary markers. The results of this review show that the first-generation urinary markers did not add much to urinary cytology. The current generation of markers is promising but larger clinical trails are needed. The future of marker development is bright with new techniques emerging, but the perfect marker is still to be found. Currently, no single marker can yet guide us in surveillance and lower the frequency of urethrocystoscopy.
    European Urology 06/2008; 53(5):909-16. DOI:10.1016/j.eururo.2007.12.006 · 12.48 Impact Factor
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