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

The cytokeratins are the intermediate filament proteins characteristic of e pithelial cells. In human cells, some 20 different cytokeratin isotypes hav e been identified. Epithelial cells express between two and ten cytokeratin isotypes and the consequent profile which reflects both epithelial type an d differentiation status may be useful in tumour diagnosis. The transitiona l epithelium or urothelium of the urinary tract shows alterations in the ex pression and configuration of cytokeratin isotypes related to stratificatio n and differentiation. In transitional cell carcinoma, changes in cytokerat in profile may provide information of potential diagnostic and prognostic s ignificance. The intensification of immunolabelling with some CK8 and CK18 antibodies may underly an active role in tumour invasion and foci of CK17-p ositive cells may represent proliferating populations. Loss of CK13 is a ma rker of grade and stage and de novo expression of CK14 is indicative of squ amous differentiation and an unfavourable prognosis. However, perhaps the m ost important recent finding is the demonstration that a normal CK20 expres sion pattern is predictive of tumour non-recurrence and can be used to make an objective differential diagnosis between transitional cell papilloma an d carcinoma. This review will consider cytokeratin expression in urothelium and discuss the application of cytokeratin typing to the diagnosis and pro gnosis of patients with TCC.