Southgate J, Harnden P, Trejdosiewicz LKCytokeratin expression patterns in normal and malignant urothelium: a review of the biological and diagnostic implications. Histol Histopathol 14: 657-664

ICRF Cancer Medicine Research Unit, Research School of Medicine, St James's University Hospital, Leeds, UK.
Histology and histopathology (Impact Factor: 2.1). 05/1999; 14(2):657-64.
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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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    • "However, in this vista, intermediate filament family proteins play an important role in the genesis of Transitional Cell Carcinoma. Cytokeratins are one of the chief structural proteins, which form the cytoplasmic network of intermediate filaments [3] and its family contains at least 20 types of cytoplasmic intermediate filaments found in epithelial cells [4]. They are expressed in a tissue-specific manner in normal organs as well as in the tumors that derived from them [5]. "
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    ABSTRACT: The aim of study was to examine the localization and distribution of cytokeratin (CK) and vimentin protein and their association with clinical outcome of the TCC patients. Expression pattern of cytokeratin and vimentin was evaluated by immunohistochemistry in TCC cases and inflammatory lesions. Cytoplasmic expression of CK was noticed in 52.17% of TCC cases and its expression was not observed in inflammatory lesions of bladder specimens. Vimentin showed expression in 69.00% cases of TCC. Significant differences were noticed in expression pattern of CK and vimentin in inflammatory lesion and Transitional Cell Carcinoma cases. Vimentin expression increased with the grade of TCC and this difference was statistically significant whereas expression of CK decreased according to the grade of TCC. Furthermore, it was also observed that expression pattern of vimentin was high in ≥55 years as compared to <55 age group patients and these differences were significant in men as compared to women. Expression pattern of CK did not show any significant relation with age and gender. Therefore, it can be concluded that cytokeratin and vimentin will be helpful markers in the early diagnosis of Transitional Cell Carcinoma/bladder carcinoma.
    Disease markers 10/2015; 2015(Article ID 204759):5. DOI:10.1155/2015/204759 · 1.56 Impact Factor
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    • "According to our own data KRT13 is less expressed in UCB. Other studies [15–18] show a downregulation of KRT13 expression in more advanced stages and in high grade UCB. Recent findings suggested an epigenetic alteration of KRT13 gene due to hypermethylation leading to diminished expression of this gene in aggressive UCB [19]. "
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    ABSTRACT: Purpose. To validate microarray data on cytokeratin 13 (KRT13) and interleukin-1 receptor antagonist (IL1RN) expression in urothelial carcinoma of the urinary bladder (UCB) and to correlate our findings with pathologic characteristics and tobacco smoking. Methods. UCB tissue samples (n = 109) and control samples (n = 14) were obtained from transurethral resection and radical cystectomy specimens. Immunohistochemical staining of KRT13 and IL1RN was performed and semiquantitative expression scores were assessed. Smoking status was evaluated using a standardized questionnaire. Expression scores were correlated with pathologic characteristics (tumor stage and grade) and with smoking status. Results. Loss of KRT13 and IL1RN expression was observed in UCB tissue samples when compared to controls (P = 0.007, P = 0.008) in which KRT13 and IL1RN expression were high. IL1RN expression was significantly reduced in muscle-invasive tumors (P = 0.003). In tissue samples of current smokers, a significant downregulation of IL1RN was found when compared to never smokers (P = 0.013). Conclusion. Decreased expressions of KRT13 and IL1RN are common features of UCB and are associated with aggressive disease. Tobacco smoking may enhance the loss of IL1RN, indicating an overweight of proinflammatory mediators involved in UCB progression. Further validation of the influence of smoking on IL1RN expression is warranted.
    Advances in Urology 07/2014; 2014:184602. DOI:10.1155/2014/184602
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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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