PURPOSE: Nuclear factor-kappaB (NF-kappaB) has been shown to be abnormally activated in some human hepatocellular carcinomas (HCCs), but most studies of NF-kappaB in patient samples have focused on the p65 subunit. Recent information has implicated IkappaB family members (e.g. Bcl-3) as possible mediators of NF-kappaB activation. Therefore, we examined the expression of all NF-kappaB family members and downstream targets in HCC. STUDY DESIGN: Archived HCCs from 30 patients were evaluated by immunohistochemistry for NF-kappaB family proteins, Bcl-3 and targets of NF-kappaB/IkappaB function. Results were validated by Western blotting in frozen paired HCC and adjacent normal tissue in a subset of cases. RESULTS: NF-kappaB p50 and p52 subunits were frequently localized to tumor cell nuclei (40 and 48%), whereas p65 positivity was infrequent. Bcl-3 was overexpressed in 90% of tumor cell nuclei compared with 26% of adjacent non-neoplastic liver (p < 0.001). CONCLUSIONS: Aberrant Bcl-3 nuclear expression occurs in the vast majority of HCCs compared with adjacent normal or cirrhotic liver tissue. Bcl-3 is known to interact with NF-kappaB p50 and p52 homodimers, and our study demonstrates very frequent nuclear colocalization of Bcl-3 and p50/p52, suggesting that the Bcl-3/p50 or Bcl-3/p52 interactions are important in HCC pathogenesis. Copyright 2007 S. Karger AG, Basel.
PURPOSE: Nuclear factor-kappaB (NF-kappaB) has been shown to be abnormally activated in some humanhepatocellular carcinomas (HCCs), but most studies of NF-kappaB in patient samples have focused on the p65 subunit. Recent information has implicated IkappaB family members (e.g. Bcl-3) as possible mediators of NF-kappaB activation. Therefore, we examined the expression of all NF-kappaB family members and downstream targets in HCC. STUDY DESIGN: Archived HCCs from 30 patients were evaluated by immunohistochemistry for NF-kappaB family proteins, Bcl-3 and targets of NF-kappaB/IkappaB function. Results were validated by Western blotting in frozen paired HCC and adjacent normal tissue in a subset of cases. RESULTS:NF-kappaB p50 and p52 subunits were frequently localized to tumor cell nuclei (40 and 48%), whereas p65 positivity was infrequent. Bcl-3 was overexpressed in 90% of tumor cell nuclei compared with 26% of adjacent non-neoplastic liver (p < 0.001). CONCLUSIONS: Aberrant Bcl-3 nuclear expression occurs in the vast majority of HCCs compared with adjacent normal or cirrhotic liver tissue. Bcl-3 is known to interact with NF-kappaB p50 and p52 homodimers, and our study demonstrates very frequent nuclear colocalization of Bcl-3 and p50/p52, suggesting that the Bcl-3/p50 or Bcl-3/p52 interactions are important in HCC pathogenesis. Copyright 2007 S. Karger AG, Basel.