Annals of Surgical Oncology

, Volume 23, Issue 2, pp 671–677 | Cite as

Verification of WFA-Sialylated MUC1 as a Sensitive Biliary Biomarker for Human Biliary Tract Cancer

  • Takayuki Yamaguchi
  • Yukihiro YokoyamaEmail author
  • Tomoki Ebata
  • Atsushi Matsuda
  • Atsushi Kuno
  • Yuzuru Ikehara
  • Junichi Shoda
  • Hisashi Narimatsu
  • Masato Nagino
Translational Research and Biomarkers



The diagnostic accuracy of biliary cytology is limited. A novel sandwich enzyme-linked immunosorbent assay that combined Wisteria floribunda agglutinin (WFA) and anti-sialylated mucin 1 (MUC1) monoclonal antibody to target bile samples was recently developed. This study was designed to verify the diagnostic accuracy of WFA-sialylated MUC1 as a sensitive biliary biomarker for human biliary tract cancer.


Bile samples from 27 patients with benign disease and 174 patients with biliary tract cancer were analyzed. A receiver-operated characteristic curve analysis for biliary WFA-sialylated MUC1 and serum CA19-9 levels was performed to determine the cutoff value for the prediction of the presence of biliary tract cancer.


Biliary WFA-sialylated MUC1 levels were significantly higher in the biliary tract cancer group compared with the benign group (P < 0.001). The cutoff value of WFA-sialylated MUC1 for discriminating biliary tract cancer was 10.5. The sensitivity of WFA-sialylated MUC1 in discriminating biliary tract cancer was much higher (82.2 %) than that of cytology (23.6 %) when this cutoff value was used. The cutoff value of serum CA19-9 for discriminating biliary tract cancer was 38 IU/L in the same cohort. All patients with biliary WFA-sialylated MUC1 and serum CA19-9 above the cutoff values had biliary tract cancer, and no patient with benign disease was categorized in this group.


Biliary WFA-sialylated MUC1 is a useful biomarker for the differentiation of biliary tract cancer. The sensitivity of WFA-sialylated MUC1 was clearly higher than that of biliary cytology. Further data collection is necessary to validate the clinical usefulness of this biomarker.


Benign Disease Biliary Stricture Extrahepatic Bile Duct Biliary Tract Cancer Bile Duct Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Tsuchiya T, Yokoyama Y, Ebata T, Igami T, Sugawara G, Kato K, et al. Randomized controlled trial on timing and number of sampling for bile aspiration cytology. J Hepatobiliary Pancreat Sci. 2014;21(6):433–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Mann DV, Edwards R, Ho S, Lau WY, Glazer G. Elevated tumour marker CA19-9: clinical interpretation and influence of obstructive jaundice. Eur J Surg Oncol. 2000;26(5):474–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Narimatsu H, Iwasaki H, Nakayama F, Ikehara Y, Kudo T, Nishihara S, et al. Lewis and secretor gene dosages affect CA19-9 and DU-PAN-2 serum levels in normal individuals and colorectal cancer patients. Cancer Res. 1998;58(3):512-8.PubMedGoogle Scholar
  4. 4.
    Matsuda A, Kuno A, Kawamoto T, Matsuzaki H, Irimura T, Ikehara Y, et al. Wisteria floribunda agglutinin-positive mucin 1 is a sensitive biliary marker for human cholangiocarcinoma. Hepatology. 2010;52(1):174–82.PubMedCrossRefGoogle Scholar
  5. 5.
    Takeuchi H, Kato K, Denda-Nagai K, Hanisch FG, Clausen H, Irimura T. The epitope recognized by the unique anti-MUC1 monoclonal antibody MY.1E12 involves sialyl alpha 2-3galactosyl beta 1-3 N-acetylgalactosaminide linked to a distinct threonine residue in the MUC1 tandem repeat. J Immunol Methods. 2002;270(2):199–209.PubMedCrossRefGoogle Scholar
  6. 6.
    Hattori M, Nagino M, Ebata T, Kato K, Okada K, Shimoyama Y. Prospective study of biliary cytology in suspected perihilar cholangiocarcinoma. Br J Surg. 2011;98(5):704–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Nakayama A, Imamura H, Shimada R, Miyagawa S, Makuuchi M, Kawasaki S. Proximal bile duct stricture disguised as malignant neoplasm. Surgery. 1999;125(5):514–21.PubMedCrossRefGoogle Scholar
  8. 8.
    Corvera CU, Blumgart LH, Darvishian F, Klimstra DS, DeMatteo R, Fong Y, et al. Clinical and pathologic features of proximal biliary strictures masquerading as hilar cholangiocarcinoma. J Am Coll Surg. 2005;201(6):862–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Wakai T, Shirai Y, Sakata J, Maruyama T, Ohashi T, Korira PV, et al. Clinicopathological features of benign biliary strictures masquerading as biliary malignancy. Am Surg. 2012;78(12):1388–91.PubMedGoogle Scholar
  10. 10.
    Gerhards MF, Vos P, van Gulik TM, Rauws EA, Bosma A, Gouma DJ. Incidence of benign lesions in patients resected for suspicious hilar obstruction. Br J Surg. 2001;88(1):48–51.PubMedCrossRefGoogle Scholar
  11. 11.
    Are C, Gonen M, D’Angelica M, DeMatteo RP, Fong Y, Blumgart LH, et al. Differential diagnosis of proximal biliary obstruction. Surgery. 2006;140(5):756–63.PubMedCrossRefGoogle Scholar
  12. 12.
    Fujita T, Kojima M, Gotohda N, Takahashi S, Nakagohri T, Konishi M, et al. Incidence, clinical presentation and pathological features of benign sclerosing cholangitis of unknown origin masquerading as biliary carcinoma. J Hepatobil Pancreat Sci. 2010;17(2):139–46.CrossRefGoogle Scholar
  13. 13.
    Ebata T, Yokoyama Y, Igami T, Sugawara G, Mizuno T, Nagino M. Review of hepatopancreatoduodenectomy for biliary cancer: an extended radical approach of Japanese origin. J Hepatobiliary Pancreat Sci. 2014;21(8):550–5.PubMedCrossRefGoogle Scholar
  14. 14.
    Huang L, Chen W, Liang P, Hu W, Zhang K, Shen S, et al. Serum CYFRA 21-1 in biliary tract cancers: a reliable biomarker for gallbladder carcinoma and intrahepatic cholangiocarcinoma. Dig Dis Sci. 2015;60(5):1273–83.PubMedCrossRefGoogle Scholar
  15. 15.
    Qin XL, Wang ZR, Shi JS, Lu M, Wang L, He QR. Utility of serum CA19-9 in diagnosis of cholangiocarcinoma: in comparison with CEA. World J Gastroenterol. 2004;10(3):427–32.PubMedGoogle Scholar
  16. 16.
    Akdogan M, Parlak E, Kayhan B, Balk M, Saydam G, Sahin B. Are serum and biliary carcinoembryonic antigen and carbohydrate antigen19-9 determinations reliable for differentiation between benign and malignant biliary disease? Turk J Gastroenterol. 2003;14(3):181-4.PubMedGoogle Scholar
  17. 17.
    Ince AT, Yildiz K, Baysal B, Danalıoğlu A, Kocaman O, Tozlu M, et al. Roles of serum and biliary CEA, CA19-9, VEGFR3, and TAC in differentiating between malignant and benign biliary obstructions. Turk J Gastroenterol. 2014;25(2):162–9.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2015

Authors and Affiliations

  • Takayuki Yamaguchi
    • 1
  • Yukihiro Yokoyama
    • 1
    Email author
  • Tomoki Ebata
    • 1
  • Atsushi Matsuda
    • 2
  • Atsushi Kuno
    • 2
  • Yuzuru Ikehara
    • 2
  • Junichi Shoda
    • 3
  • Hisashi Narimatsu
    • 2
  • Masato Nagino
    • 1
  1. 1.Division of Surgical Oncology, Department of SurgeryNagoya University Graduate School of MedicineNagoyaJapan
  2. 2.Research Center for Medical Glycoscience (RCMG)National Institute of Advanced Industrial Science and Technology (AIST), AIST Central 2TsukubaJapan
  3. 3.Medical Sciences, Faculty of MedicineUniversity of TsukubaTsukubaJapan

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