Cytokeratins in the histological diagnosis of malignant tumors

Cytokeratins, which comprise a multigene family of 20 related polypeptides (CKs 1-20), are constituents of the intermediate filaments of epithelial cells, in which they are expressed in various combinations depending on the epithelial type and the degree of differentiation. Of these, CK 19 (400 amino acids; 44.1 kilodaltons) is an example of a widely distributed CK, being expressed in various epithelia, including many simple epithelia. In contrast, the recently identified CK 20 (424 amino acids; 48.6 kilodaltons) is essentially confined to gastrointestinal epithelia, the urothelium and Merkel cells. The differential expression of individual CKs in various types of carcinomas makes them useful markers for histopathological carcinoma subtyping, providing relevant information concerning the differentiation and origin of carcinomas, especially when tumors first present as metastases. The CKs that are of particular value for differential diagnosis include CK 20, as it is mainly expressed in carcinomas derived from CK 20-positive epithelia; it is also found in bile-tract, pancreatic and mucinous ovarian adenocarcinomas, being absent in most other carcinomas. In certain carcinoma types, the changes in the expression of individual CKs that may occur during tumor progression could be of prognostic relevance. It remains to be established whether the serological detection of fragments of not only widely distributed but also more restrictedly expressed CKs may provide useful serological tumor markers in the future.