Article

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.
Source: PubMed

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.

1 Bookmark
 · 
123 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Papillary urothelial neoplasms (PUNs) of the urinary bladder comprise a heterogeneous spectrum of ‘continuous’ lesions in which the assessment of an accurate histological grade and tumor stage is necessary for an adequate clinical management of patients. Recently, the 1998 World Health Organization/International Society of Urologic Pathologists (WHO/ISUP) Consensus Classification and the 1999 WHO classification proposed a new malignancy grading scheme based mainly on morphometric studies. In accordance with these grading systems, two major categories of PUNs were distinguished: low-grade and high-grade. Concerning the specific subgroup of low-grade tumors two other entities were defined: PUNs of low malignant potential (PUNLMP) and low-grade papillary urothelial carcinomas (LGPUC). In long-term follow-up programmes, PUNLMP have demonstrated a low recurrence rate and a minimal risk for tumor progression in comparison with LGPUC. However, grade assessment is a subjective decision and, on occasion, the application of criteria by uropathologists is difficult due to tumor heterogeneity and to the existence of a variable number of cases situated between consecutive groups. As a consequence, to determine a better correlation with patient outcome other predictive markers have also been investigated. Among these factors, the prognostic significance of classical clinicopathological, morphometric, cytometric, immunohistochemical and molecular markers have been widely reported. In the current review, we summarize the comparative value of all of these markers in predicting tumor recurrences and progression in low-grade papillary urothelial bladder neoplasms, including our own personal experience.
    Current Diagnostic Pathology 06/2005; 11(3):141-150. DOI:10.1016/j.cdip.2005.01.002
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Actin is a globular protein which forms long filaments in the eukaryotic cytoskeleton, whose roles in cell function include structural support, contractile activity to intracellular signalling. We model actin filaments as two chains of one-dimensional binary-state semi-totalistic automaton arrays to describe hypothetical signalling events therein. Each node of the actin automaton takes state `0' (resting) or `1' (excited) and updates its state in discrete time depending on its neighbour's states. We analyse the complete rule space of actin automata using integral characteristics of space-time configurations generated by these rules and compute state transition rules that support travelling and mobile localizations. Approaches towards selection of the localisation supporting rules using the global characteristics are outlined. We find that some properties of actin automata rules may be predicted using Shannon entropy, activity and incoherence of excitation between the polymer chains. We also show that it is possible to infer whether a given rule supports travelling or stationary localizations by looking at ratios of excited neighbours are essential for generations of the localizations. We conclude by applying biomolecular hypotheses to this model and discuss the significance of our findings in context with cell signalling and emergent behaviour in cellular computation.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To examine the kinetics of growth, differentiation and senescence of normal human urothelium in an organoid-like culture model.Materials and Methods: Micro-dissected normal human urothelium explants were grown on porous membranes pretreated with various matrix components. Between 5 and 30 days of culture, cell proliferation was assessed by BrdU incorporation. Differentiation was evaluated on the basis of cytokeratin (Ck) and uroplakin (UP) expression. Epidermal growth factor family mRNA expression was monitored during explant outgrowth. Senescence was assessed by measuring endogenous β-galactosidase activity and p16INK4a mRNA expression.Results: Collagen IV was the most efficient matrix component for urothelial cell expansion. BrdU incorporation by urothelial cells was 5% between 15 and 30 days, corresponding to steady-state urothelium in vivo. Heparin-binding EGF (HB-EGF), Amphiregulin (AR) and Transforming Growth Factor α (TGFα) expression correlated with increased cell proliferation. UPII expression was stable throughout culture. P16INK4a mRNA expression and β-galactosidase activity increased on day 25, giving signs of senescence.Conclusions: This model retains many characteristics of the urothelium in vivo. It can be used for pharmacological studies between 15 to 25 days and to study mechanisms such as wound healing, proliferation and senescence.
    European Urology 06/2004; 45(6):799-805. DOI:10.1016/S0302-2838(04)00006-5 · 12.48 Impact Factor