Early diagnosis and curative surgical resection therefore provide the only chance of long-term survival for patients with ICC. Despite advances and refinements, no tumour marker has shown satisfactory sensitivity or specificity for early detection of ICC, for estimating research only extent of disease, or for monitoring response to treatment. Thus, a reliable marker for ICC would be a valuable addition to available diagnostic tests. Cytokeratins are cytoskeletal intermediate filaments present in almost all normal and malignant epithelial cells (Moll et al, 1992). Characteristic combinations of cytokeratin polypeptides are expressed in different epithelia depending on the organ and/or type of differentiation (Osborn et al, 1986; Moll et al, 1992). Epithelial cells in the liver also express characteristic cytokeratins.

In normal human liver, hepatocytes express cytokeratins 8 and 18, while bile duct cells also contain cytokeratins 7 and 19 (Osborn et al, 1986; Balaton et al, 1988; Johnson et al, 1988; Moll et al, 1992). Since this cytokeratin pattern ordinarily is preserved during neoplastic transformation, ICC and the CC component of c-HCC-CC contain cytokeratin 19, while HCC does not (Osborn et al, 1986; Balaton et al, 1988; Johnson et al, 1988; Moll et al, 1992). Therefore, a soluble fragment of cytokeratin 19, CYFRA 21-1, may be a useful marker for ICC. Kashihara et al (1998) have reported that high serum concentrations of CYFRA 21-1 in patients with large liver cancer would suggest the existence of ICC rather than HCC, since serum concentration of CYFRA 21-1 markedly elevated in four patients with ICC, compared with that in 13 patients with HCC.

However, all the four patients had severe advanced and unresectable tumours. We evaluated serum CYFRA 21-1 concentrations in 23 patients with various stage ICC to determine the usefulness of CYFRA 21-1 as a marker for diagnosis of ICC, and also to identify relation between CYFRA 21-1 levels and various histological features including components of tumour staging schema. Tumour markers such as CA 19-9 and CEA can be used in combination not only for diagnosis of gastrointestinal malignancies but also for monitoring during and in follow-up treatment. Some investigators have recommended that a possible diagnosis of ICC should be considered when a hepatic tumour is associated with high-serum CEA concentration, since serum CEA had relatively high sensitivity in patients with ICC (Kawarada and Mizumoto, 1984; Wang et al, 1994).

Kubo et al (1995) reported that a high-serum CEA concentration strongly suggests ICC in patients with hepatolithiasis, even when no hepatic tumour is detected. Generally, however, serum CEA concentrations are elevated in only 20�C45% of patients with ICC (Yamanaka et al, 1995; Brefeldin_A Chu et al, 1997; Harrison et al, 1998; Kashihara et al, 1998; Kim et al, 1999; Uenishi et al, 2001).