Intrahepatic cholangiocarcinoma with increased serum CYFRA 21-1 level

Abstract

CYFRA 21-1 is a fragment of cytokeratin 19 (CK 19). Four patients with large intrahepatic (or peripheral) cholangiocarcinoma (CC) and high serum levels of CYFRA 21-1 (normal, < or = 2 ng/ml) are reported. CYFRA 21-1 levels exceeded 9 ng/ml in all 4 patients. Carcinoembryonic antigen (CEA), was high in 1 (CEA; normal range, < or = 5.0 ng/ml) and carbohydrate antigen 19-9 (CA 19-9) was high in 3 (CA19-9; normal range, < or = 36 U/ml). We also measured serum levels of CYFRA 21-1 in 13 patients with hepatocellular carcinoma (HCC) more than 5 cm in diameter. Levels of CYFRA 21-1 exceeded 2 ng/ml in 9 of the HCC patients and were higher than 9 ng/ml in 2 of the HCC patients. Levels of alpha fetoprotein (AFP) and/or protein induced by vitamin K absence or antagonist II (PIVKA II) were elevated in all HCC patients (AFP, PIVKA II, respectively; normal range, < or = 10.0 ng/ml and < or = 0.1 AU/ml) CYFRA 21-1 levels were measured twice or three times during the clinical course in 2 CC patients and in 6 HCC patients, and increased gradually with tumor growth in the 2 CC patients and in 3 of the 6 HCC patients. Marked increases in serum CYFRA 21-1 levels in patients with large liver cancers, particularly in those with normal levels of AFP and PIVKA II, would suggest the existence of intrahepatic CC rather than HCC.

Cytokeratin-19 fragments in serum (CYFRA 21-1) as a marker in primary liver cancer

“…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 -45% of patients with ICC (Yamanaka et al, 1995;Chu et al, 1997;Harrison et al, 1998;Kashihara et al, 1998;Kim et al, 1999;Uenishi et al, 2001). In the present study, serum CEA also showed a low sensitivity for ICC (34.8%).…”

“…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.…”

“…In addition to lung cancer, CYFRA 21-1 has been reported to be a useful marker for cervical carcinoma (Gaarenstroom et al, 1995;Doweck et al, 2000), oesophageal cancer (Brockmann et al, 2000;Kawaguchi et al, 2000), breast cancer (Nakata et al, 2000), gastric cancer (Nakata et al, 1996), and bladder cancer - (Sanchez-Carbayo et al, 1999). Little is known, however, about the clinical significance of serum CYFRA 21-1 in 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.…”

The Value of Molecular Biomarkers in Biliary Tract Cancer in the Era of Targeted Therapy

“…20 Circulating fragment, the cytokeratin 19, using the CYFRA 21-1 assay has been shown to be elevated in CC, with a sensitivity of 74.7% and specificity of 92.2%. 21,22 It has been suggested that the increased concentration of CYFRA 21-1 might represent circulating tumor cells and that surgery alone may not be able to control CC in patients with a high CYFRA 21-1 concentration. 22 In a study published in this journal by Chapman et al, CYFRA 21-1 and CA 19-9 levels have been evaluated in 66 patients with BTC (PSC related, 6; sporadic, 60), 39 patients with benign biliary disease, and 19 patients with PSC.…”

“…Since the initial report of CYFRA 21-1 by Kashihara et al in 4 cases of biliary cancer, there are scant data of this biomarker. 21 The sensitivity of CYFRA 21-1 in BTC is poor. As an isolated test result, this will make a poor biomarker for diagnosis, though it is possible that it may have a role as a part of a biomarker panel, including CA 19-9.…”