Little is known, however, about the clinical significance of serum CYFRA 21-1 in selleck primary liver cancer, although Kashihara et al (1998) have reported marked high concentration of serum CYFRA 21-1 in four patients with severe advanced ICC. As cytokeratin 19 is abundant in ICC (Osborn et al, 1986; Balaton et al, 1988; Johnson et al, 1988; Moll et al, 1992), serum CYFRA 21-1 may be useful for diagnosing and monitoring these neoplasms. In assessing relations to histologic type and pathologic stage in primary liver cancer, we compared serum CYFRA 21-1 with three widely used tumour markers: AFP, CEA, and CA 19-9 in large number of patients with primary liver cancer. MATERIALS AND METHODS Patients The study was performed retrospectively using consecutively obtained samples from 187 patients who underwent hepatic resection for primary liver cancer.

Serum samples were collected just before surgery and were stored at ?80��C until analysis. All patients were referred to the Department of Hepato-Biliary-Pancreatic Surgery at Osaka City University Hospital between 1994 and December 2001, and had histologically confirmed primary liver cancer. Their characteristics are listed in Table 1. The patient population included 164 patients with HCC and 23 with ICC; of the latter, six had c-HCC-CC. Tumour stage was defined according to the pathologic tumour-nodes-metastasis (pTNM) classification proposed by the International Union Against Cancer (Sobin and Wittekind, 1997). Table 1 Characteristics of 187 patients with primary liver cancer and 87 controls with benign liver disease Control blood samples were obtained from 87 patients with nonmalignant liver diseases (Table 1).

These patients were diagnosed using clinical, radiologic, and laboratory criteria. Diagnoses of cirrhosis were confirmed by liver biopsy specimen examination. This study was conducted in accordance with the Helsinki Declaration and the guidelines of the Ethics Committee of our institution. Informed consent was obtained from each patient. Measurement of tumour markers We measured CYFRA 21-1 using an electrochemiluminescent immunoassay (ECLIA). The assay, using an Elecsys 2010 analyser (Roche Diagnostics, Basel, Switzerland), is based on the ability of an electrochemically luminescent molecule, a tris(2,2��-bipyridyl)ruthenium (II) complex, to be repeatedly excited by tripropylamine.

The system can be applied to both competitive and sandwich-format immunoassays. CYFRA 21-1 was recognised by two mouse monoclonal antibodies, a biotinylated monoclonal cytokeratin 19-specific antibody (Ks 19-1) and a monoclonal cytokeratin 19-specific antibody (BM 19-21), directed against Brefeldin_A two different epitopes of a fragment of cytokeratin 19. In the first incubation, Ks 19-1 and BM 19-21 labelled with a ruthenium complex were allowed to react, forming a sandwich complex.