Expression Levels and Significance of Nuclear Factor-kB and Epidermal Growth Factor Receptor in Hepatolithiasis Associated with Intrahepatic Cholangiocarcinoma

Background: An increasing incidence of cholangiocarcinoma (CCA) and CCA mortality rates has been observed around the world. Patients with intrahepatic biliary stones have a 10% risk of developing CCA, and up to 70% of patients with histologically confirmed CCA have hepatolithiasis. Few previous studies have addressed the associations between the expression of nuclear factor (NF)-kB and epidermal growth factor receptor (EGFR) and clinicopathological prognosis in patients with hepatolithiasis-associated intrahepatic CCA. Aims: This study was designed to investigate the clinicopathological and prognostic significance of NF-kB and EGFR expression in hepatolithiasis-associated intrahepatic CCA and hepatolithiasis. Methods: A total of 90 liver specimens were immunohistochemically stained for NF-kB and EGFR expression, and the characteristics of 90 individual patients were retrospectively reviewed. Results: Differences in the positive rates of NF-kB and EGFR expression between the hepatolithiasis-associated intrahepatic CCA group, intrahepatic lithiasis group, and control group were found to be statistically significant. EGFR expression was closely associated with the degree of differentiation and depth of invasion (p < 0.05). The 1-, 3-, and 5-year overall survival rates were respectively 42.8, 21.0, and 10.3% in intrahepatic CCA groups. The survival rate of the EGFR-negative group was higher than in the EGFR-positive group (p < 0.01). Lymph node metastasis (HR 1.24, 95% CI 1.02-1.51) and EGFR positivity (HR 1.74, 95% Cl 1.30-2.23) were associated with decreases in the survival rate. Conclusion: The expression of NF-KB may be an early step in intrahepatic cholangiocarcinogenesis. Overexpression of EGFR is associated with the degree of malignancy and with poor prognosis. NF-KB and EGFR may cooperate during intrahepatic cholangiocarcinogenesis and progression. Lymph node metastasis and EGFR positivity were associated with decreases in the survival rate. Copyright (C) 2013 S. Karger AG, Basel