Mac‐2‐binding protein is a diagnostic marker for biliary tract carcinoma

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Abstract
BACKGROUND Biliary tract carcinoma is a deadly disease, accounting for nearly 4500 malignancy‐related deaths each year in the United States. Early detection has the potential to improve survival for patients with biliary tract malignancies, enabling curative surgical resection. Early detection approaches would benefit from an accurate, minimally invasive diagnostic test. To identify novel diagnostic markers, the authors recently completed a comprehensive proteomic study of bile samples from patients with biliary carcinoma. One of the proteins identified by tandem mass spectrometry was Mac‐2‐binding protein (Mac‐2BP). The authors evaluated the performance of Mac‐2BP and its ligand, galectin‐3, as diagnostic markers for patients with biliary carcinoma. METHODS Levels of Mac‐2BP, galectin‐3, and CA19‐9 were measured using an enzyme‐linked immunosorbent assay (ELISA) in bile samples from patients with biliary tract carcinoma (n = 26), benign biliary conditions (n = 32), and primary sclerosing cholangitis (n = 20). Serum levels of Mac‐2BP and galectin‐3 also were determined using ELISA. Mac‐2BP tissue expression was investigated by immunohistochemical methods using a biliary carcinoma tissue microarray. RESULTS Biliary Mac‐2BP levels were elevated by a factor of ∼3 in the biliary carcinoma group compared with the group of patients who had PSC or another type of nonneoplastic biliary disease. In contrast, Mac‐2BP levels were not elevated in serum samples from patients with biliary carcinoma. According to the immunohistochemical analysis, Mac‐2BP was expressed in 34 of 36 patients (94.4%) with biliary tract carcinoma. As a diagnostic marker for biliary carcinoma, Mac‐2BP levels were as accurate as biliary CA19‐9 levels, with an area under the curve (AUC) of 0.70 on receiver operator characteristic analysis. The use of both of these bile markers in combination, however, led to significantly better diagnostic accuracy compared with the accuracy achieved using CA19‐9 alone (AUC, 0.75; P < 0.001). Serum and biliary galectin‐3 levels did not differ in the biliary carcinoma group relative to the control groups. CONCLUSIONS Biliary Mac‐2BP levels, especially when used in conjunction with biliary CA19‐9 levels, showed promise as a novel diagnostic marker for biliary tract carcinoma. Cancer 2004. © 2004 American Cancer Society.