Circulating CYFRA 21-1 is a Specific Diagnostic and Prognostic Biomarker in Biliary Tract Cancer.
BACKGROUND: Biliary tract cancer (BTC) has a poor prognosis, in part related to difficulties in diagnosis. Cytokeratin 19 (CK19) is a constituent of the intermediate filament proteins of epithelial cells. CK19 fragments (CYFRA 21-1) are rarely identified in the blood of healthy individuals. We assessed the utility of CYFRA 21-1 as a diagnostic and prognostic marker of BTC.  METHODS: Blood was prospectively collected from patients with benign biliary disease (n = 39), primary sclerosing cholangitis (n = 19), PSC-related cholangiocarcinoma (n = 6) and sporadic BTC (n = 60). CYFRA 21-1 levels were measured in duplicate by ELISA.  RESULTS: CYFRA 21-1 (≥ 1.5 ng/mL) had a sensitivity of 56% and specificity of 88%, compared with figures of 79% and 78% for CA 19-9 (≥ 37U/mL). Using a higher cut-off of 3 ng/mL, CYFRA 21-1 had a sensitivity of 30% and specificity of 97%. Combination of CYFRA 21-1 (≥ 1.5 ng/mL) and CA 19-9 (≥ 37 U/mL) resulted in sensitivity and specificity of 45% and 96%. In contrast to CA 19-9, CYFRA 21-1 (≥ 3.0 ng/mL) alone was a strong predictor of prognosis (median survival 2 months vs 10 months, p = 0.001).  CONCLUSION: Elevated circulating CYFRA 21-1 is a specific, but less sensitive diagnostic marker than CA 19-9, predicts a poor outcome and may act as a surrogate marker of circulating tumor cells in BTC. Further prospective studies of its utility in assessing operability and response to chemotherapy are needed.
UCL Institute of Hepatology, Royal Free Campus, UCL Medical School.
Michael H
MH
Chapman
Neomal S
NS
Sandanayake
Fausto
F
Andreola
Dipok K
DK
Dhar
George J
GJ
Webster
James S
JS
Dooley
Stephen P
SP
Pereira