Chapman Michael H, Sandanayake Neomal S, Andreola Fausto, Dhar Dipok K, Webster George J, Dooley James S, Pereira Stephen P
UCL Institute of Hepatology, Royal Free Campus, UCL Medical School.
J Clin Exp Hepatol. 2011 Jun;1(1):6-12. doi: 10.1016/S0973-6883(11)60110-2.
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.
胆管癌（BTC）预后较差，部分原因与诊断困难有关。细胞角蛋白19（CK19）是上皮细胞中间丝蛋白的组成成分。CK19片段（CYFRA 21-1）在健康个体血液中很少被检测到。我们评估了CYFRA 21-1作为BTC诊断和预后标志物的效用。方法：前瞻性收集良性胆道疾病患者（n = 39）、原发性硬化性胆管炎患者（n = 19）、PSC相关胆管癌患者（n = 6）和散发性BTC患者（n = 60）的血液。采用酶联免疫吸附测定法（ELISA）对CYFRA 21-1水平进行双份测定。结果：CYFRA 21-1（≥1.5 ng/mL）的敏感性为56%，特异性为88%，而糖类抗原19-9（CA 19-9，≥37U/mL）的敏感性和特异性分别为79%和78%。采用3 ng/mL的更高临界值时，CYFRA 21-1的敏感性为30%，特异性为97%。CYFRA 21-1（≥1.5 ng/mL）与CA 19-9（≥37 U/mL）联合使用时，敏感性和特异性分别为45%和96%。与CA 19-9不同，单独的CYFRA 21-1（≥3.0 ng/mL）是预后的有力预测指标（中位生存期2个月对10个月，p = 0.001）。结论：循环CYFRA 21-1升高是一种特异性的，但比CA 19-9敏感性较低的诊断标志物，提示预后不良，可能作为BTC循环肿瘤细胞的替代标志物。需要进一步前瞻性研究其在评估可切除性和化疗反应方面的效用。
