Aims: Intrahepatic cholangiocarcinoma (ICC) is a primary hepatic malignancy derived from cholangiocytes. The survival rate of ICC patients is very low, and conventional chemotherapy is not effective in prolonging long-term survival. Adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporters mediate the transport of various substances in several cellular processes. The expression of ABCB1, ABCC1 and ABCG2 has been implicated in multidrug resistance and poor prognosis in several types of cancer. The aim of this study was to examine their expression in normal cholangiocytes and ICC tissues.
Methods and results: Immunohistochemistry was employed to evaluate the expression of these transporters in 60 cases of ICC with respect to clinicopathological features and patient outcome. The proportions of cases with loss of ABCB1, ABCC1 and ABCG2 expression were 93.3%, 68.3% and 50%, respectively. Only the loss of ABCG2 was related to a worse prognosis (P = 0.031), and was associated with lymph node involvement (P = 0.003) and higher tumour grade (P = 0.028). Furthermore, multivariate analysis showed that the loss of ABCG2 expression was an independent prognostic factor in patients with moderately or poorly differentiated ICC (P = 0.02).
Conclusions: These results suggest that ABCG2 may be involved in cholangiocarcinogenesis; the loss of its expression may enhance tumour progression and contribute to aggressive growth of ICC.
© 2011 Blackwell Publishing Limited.