Mucin core protein expression in extrahepatic bile duct carcinoma is associated with metastases to the liver and poor prognosis

Abstract

BACKGROUND. Curative resection does not guarantee long term survival for the patient with extrahepatic bile duct carcinoma because of the possibility of metastases to the liver (LM). Expression of mucin core protein-1 (MUC1), sialyl-Le(x), and sialosyl-Tn in bile duct carcinoma was determined and compared with LM and prognosis. METHODS. Immunohistochemical expression of MUC1, sialyl-Le(x), and sialosyl-Tn in 73 extrahepatic bile duct tumors was analyzed using the DF3, FH6, and TKH2 monoclonal antibodies, respectively. Scoring was based on the percentage of immunoreactive cells: negative, low expression (≤25% immunoreactive cells), and high expression (>25%). RESULTS. High expression of MUC1, sialyl-Le(x), and sialosyl-Tn was observed in 68.5%, 34.2%, and 54.8%, respectively, of 73 cases. Patients with tumors showing high expression of MUCl had a higher rate of LM (48.9%) and a significantly shorter survival period (median survival time, 17.8 months) compared with patients with tumors showing low (incidence of LM, 9.1%; median survival time, >100 months) or negative (incidence of LM, 11.1%; median survival time, 52.9 months) expression of MUC1 (P < 0.01). However, the survival period of patients with tumors showing high, low, or negative expression of sialyl-Le(x) or of sialosyl-Tn did not differ significantly. High MUCl expression correlated with LM by logistic regression analysis and emerged as an independent prognostic factor in stepwise multivariate analysis. CONCLUSIONS. The results of the current study demonstrate that high expression of MUC1 correlates with LM and poor outcome in patients with extrahepatic bile duct carcinoma.