In this respect, serum is CP-690550 supplier a difficult target to develop high-specificity diagnosis markers. In this context, CA19-9 and CEA can also be expected to be useful for bile diagnosis. Unfortunately, the sensitivity of CA19-9 is not high enough, and that of CEA is still lower.4, 6, 8, 9 At present, however, CA19-9 is regarded as a “high-sensitivity” marker for the bile diagnosis of CC, although the reported diagnostic scores are not satisfactory; i.e., 65.0% (sensitivity), 69.0% (specificity), and 0.69 (area under the curve [AUC]).7 On the other hand, imaging techniques such as ultrasonography, computed tomography, and magnetic resonance

cholangiography are also performed as well as pathological diagnosis for confirmation of CC. However, this diagnosis of CC is difficult because of its location, size, and desmoplastic characteristics.4-6 Regarding the diagnosis of LY2109761 order CC, biliary cytology and brush cytology are performed routinely, although the sensitivity of exfoliative biliary cytology is generally low (40%-69%).10-12

Thus, a novel biological diagnostic marker for CC is needed to provide a fully workable method to identify the lesion at as early a stage as possible. Aberrant glycosylation is often associated with individual steps of carcinogenesis and progression.13, 14 For example, CA19-9 is a representative carbohydrate antigen, sialyl-Lea, whose expression is associated closely with cancers originating from digestive tissues. Critically, however, core proteins that carry this classic epitope have not been characterized fully. By contrast, α-fetoprotein (AFP) has been shown to function as a good diagnostic marker of hepatocellular carcinoma (HCC), and

its sensitivity and specificity have been improved significantly by combining measurement of AFP find more level with Lens culinaris agglutinin reactivity (AFP-L3).15, 16 AFP-L3 is defined as a glycoprotein carrying biantennary N-glycan(s) having a α1,6 core fucose, whose expression is relatively low in liver cirrhosis. This difference in expression emphasizes the importance of glycosylation change (glyco-alteration) occurring on the same protein.17 Thus, glyco-alteration of particular glycoproteins has attracted increasing attention among biomarker investigators. We recently developed a simple and ultrasensitive procedure for differential glycan profiling based on a lectin microarray.18-20 This novel array technology enables a straightforward, high-throughput glycan analysis with multiplex lectins that can target even formalin-embedded small tissue sections (<1.5 mm in diameter, 5 μm in thickness).21 Using this advanced technology, we identified Wisteria floribunda agglutinin (WFA) as the best probe to detect glyco-alteration in ICC and to distinguish the expression in ICC lesions from that in normal specimens. We further identified mucin 1 (MUC1) as a potential ICC-specific glycoprotein marker that carries WFA-positive glycans.