Serum CYFRA 21-1 in Biliary Tract Cancers: A Reliable Biomarker for Gallbladder Carcinoma and Intrahepatic Cholangiocarcinoma

Dig Dis Sci. 2015 May;60(5):1273-83. doi: 10.1007/s10620-014-3472-0. Epub 2014 Dec 9.

Abstract

Background: Biliary tract cancers encompass gallbladder carcinoma, and intrahepatic, perihilar and distal cholangiocarcinoma. Upregulated serum CYFRA 21-1 has been reported in intrahepatic cholangiocarcinoma.

Aims: The present study aimed to explore the clinical significance of serum CYFRA 21-1 in all biliary tract cancer subtypes.

Methods: Serum CYFRA 21-1, carbohydrate antigen 19-9 and carcinoembryonic antigen were quantitated preoperatively, postoperatively and during follow-up in 134 malignant and 52 benign patients. Receiver operator characteristic curves of biomarkers were analyzed. Level of CYFRA 21-1 was correlated with patients' clinicopathological features and follow-up data.

Results: CYFRA 21-1 was significantly upregulated in biliary malignancies, and expressional difference existed between these subtypes. Based on the maximal Youden's index, cutoff values were selected (ng/mL): 2.61 for biliary tract cancers (sensitivity 74.6 % and specificity 84.6 %); 3.27 for intrahepatic cholangiocarcinoma (75.6 and 96.2 %) and gallbladder carcinoma (93.7 and 96.2 %); 2.27 for perihilar cholangiocarcinoma (71.0 and 71.2 %); and 2.61 for distal cholangiocarcinoma (63.3 and 84.6 %). CYFRA 21-1 showed better diagnostic performance than other biomarkers in gallbladder carcinoma and intrahepatic cholangiocarcinoma; its performance was not inferior to that of the combination of these three biomarkers and declined after curative resection and re-elevated when tumor recurred, which was correlated with tumor aggressiveness and TNM stage; it was an independent predictor for 1-year recurrence-free survival and overall survival on multivariate analysis.

Conclusion: Serum CYFRA 21-1 represents a reliable biomarker for gallbladder carcinoma and intrahepatic cholangiocarcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / blood*
  • Area Under Curve
  • Bile Duct Neoplasms / blood*
  • Bile Duct Neoplasms / mortality
  • Bile Duct Neoplasms / pathology
  • Bile Duct Neoplasms / surgery
  • Bile Ducts, Intrahepatic / pathology
  • Bile Ducts, Intrahepatic / surgery
  • Biomarkers, Tumor / blood*
  • CA-19-9 Antigen / blood
  • Carcinoembryonic Antigen / blood
  • Chi-Square Distribution
  • Cholangiocarcinoma / blood*
  • Cholangiocarcinoma / mortality
  • Cholangiocarcinoma / pathology
  • Cholangiocarcinoma / surgery
  • Disease-Free Survival
  • Female
  • Gallbladder Neoplasms / blood*
  • Gallbladder Neoplasms / mortality
  • Gallbladder Neoplasms / pathology
  • Gallbladder Neoplasms / surgery
  • Humans
  • Kaplan-Meier Estimate
  • Keratin-19 / blood*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Staging
  • Odds Ratio
  • Predictive Value of Tests
  • Proportional Hazards Models
  • ROC Curve
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Up-Regulation

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CA-19-9 Antigen
  • Carcinoembryonic Antigen
  • Keratin-19
  • antigen CYFRA21.1