CD40 and CD154 Expression in Hepatocellular Carcinomas

ABSTRACT

PURPOSE: CD40 expression has been reported in a variety of cells, including antigen presenting cells (dendritic cells), B lymphocytes, monocytes, and many epithelial malignancies (breast, lung, ovary, bladder, and melanoma). The interaction of CD40 and its natural ligand (CD154) is well known in the adaptive immune response. The CD40-CD154 pathway appears to have diverse effects in malignant disease. In this study, we investigated the expression of CD40 and CD154 and evaluated their clinical implication in hepatocellular carcinomas (HCC). METHOD: Immunohistochemical staining was performed for CD40 and CD154 in 96 surgically resected HCCs using the tissue microarray method. The clinicopathological data and outcomes were reviewed and compared to the expression of CD40 and CD154. RESULTS: Positive expression of CD40 and CD154 was observed in 64.2% and 37.5% of cases, respectively. Overexpression, defined by the stain intensity and area of CD40 staining had a positive correlation with tumor cell proliferation activity as measured by the Ki-67 labeling index (p=0.013) and CD154 had a similar tendency (p=0.094). CD40 overexpression was observed frequently in small sized HCCs (p=0.046). There were no other clinicopathological factors that were significantly correlated with CD40 and CD154 expression. CD40 overexpression was correlated with a poor overall survival according to the univariate analysis (p=0.054) and multivariate analysis (p=0.035). CD154 overexpression was not correlated with the overall survival rate. CONCLUSION: The results of this study showed that CD40 expression correlated with a more aggressive tumor potential in patients with HCC. CD 40 overexpression might provide a novel prognostic marker for survival in patients with HCC.