Cytokeratins as tumor markers - Molecular and clinical data with focus on TPS

Cytokeratins, which are biochemically related to the intermediate filament proteins, are found in epithelial cells and constitute an intracellular net work of filamentous structures. At present 20 different cytokeratin protein s are known and these can be divided into two groups: cytokeratins 1-8, typ e II (53-68 kDa, neutral to basic proteins) and cytokeratins 9-20, type I ( 40-56 kDa, acidic proteins). Cytokeratins 8, 18 and 19 are the most abundan t cytokeratins in carcinomas. The expression of cytokeratins varies with ep ithelial cell type, extent of differentiation and development of the tissue . The most applied cytokeratin markers reported for different clinical appl ications are TPA, CYFRA 21-1 and TPS. TPA is a polyclonal based assay detec ting a mixture of cytokeratins 8, 18 and 19. CYFRA 21-1 is a monoclonal bas ed assay measuring soluble fragments of cytokeratin 19. TPS measures an ant igenic determinant associated with soluble fragments of human cytokeratin 1 8. The clinical value of the determination of soluble cytokeratin 18 fragme nts by the TPS assay lies in the early detection of recurrence and the quic k assessment of the efficacy of therapy response. TPS is an activity marker and thus by following the patients with repeated testing, the oncologist m ay obtain critical information regarding the growth activity in cases where the presence of a tumor is already known. Furthermore, TPS and the other c ytokeratin markers may accurately predict disease status prior to conventio nal methods and thus offer a reliable tool for a more efficient treatment.