Wisteria floribunda agglutinin-positive mucin 1 is a sensitive biliary marker for human cholangiocarcinoma.
Cholangiocarcinoma (CC) is an aggressive malignant tumor for which useful markers are not presently available for early and precise diagnosis. The aim of this study was therefore to identify a high-performance diagnostic marker with a special focus on glyco-alteration of glycoproteins. In the course of study, we found that Wisteria floribunda agglutinin (WFA) is the best probe to differentiate intrahepatic cholangiocarcinoma (ICC) lesions from normal bile duct epithelia (BDE) (P < 0.0001). The subsequent histochemical study confirmed ICC-specific WFA staining on 165 tissue specimens. On the other hand, the WFA staining was shown to be closely associated with that of MY.1E12 established previously against sialylated mucin 1 (MUC1) by double-staining experiments. Moreover, glyco-alteration of MUC1 could be verified by western blotting of WFA-captured bile samples from patients with CC patients. Thus, we attempted to construct an enzyme-linked immunosorbent assay system for more convenient CC diagnosis, where WFA-coated plates, the specific monoclonal antibody MY.1E12, and the bile specimens from CC including ICC (n = 30) and benign diseases (n = 38) were combined. As a result, CC was clearly distinguished from benign diseases with statistical scores (sensitivity = 90.0%, specificity = 76.3%, and area under the curve = 0.85). As a particular note, the obtained sensitivity is the highest score among those having been so far reported.


CONCLUSIONS
Our approach focusing significant glyco-alteration of a particular glycoprotein yielded a novel diagnostic system for CC with satisfactory clinical scores.
Matsuda
Atsushi
A
Research Center for Medical Glycoscience, National Institute of Advanced Industrial Science and Technology, AIST Tsukuba Central 2, Tsukuba, Ibaraki, Japan.
Kuno
Atsushi
A
Kawamoto
Toru
T
Matsuzaki
Hideki
H
Irimura
Tatsuro
T
Ikehara
Yuzuru
Y
Zen
Yoh
Y
Nakanuma
Yasuni
Y
Yamamoto
Masakazu
M
Ohkohchi
Nobuhiro
N
Shoda
Junichi
J
Hirabayashi
Jun
J
Narimatsu
Hisashi
H
D000911:Antibodies, Monoclonal / Q000276:immunology; D001646:Bile / Q000737:chemistry*; D001650:Bile Duct Neoplasms / Q000175:diagnosis*; D001653:Bile Ducts, Intrahepatic; D014408:Biomarkers, Tumor / Q000032:analysis*; D018281:Cholangiocarcinoma / Q000175:diagnosis*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D018396:Mucin-1 / Q000032:analysis*; D037121:Plant Lectins / Q000737:chemistry* / Q000276:immunology; D040081:Protein Array Analysis; D034781:Receptors, N-Acetylglucosamine / Q000737:chemistry* / Q000276:immunology; D013194:Staining and Labeling
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D018396:Mucin-1; D037121:Plant Lectins; D034781:Receptors, N-Acetylglucosamine; C040129:wisteria lectin