Clinicopathological significance of nuclear factor-κB activation in hepatocellular carcinoma

Aim: Nuclear factor-κB (NF-κB) is a critical signaling mediator in inflammation, apoptosis resistance and oncogenesis. It has been reported that NF-κB is activated in several cancers, including hepatocellular carcinoma (HCC). Studies of genetic disruptions in mice also suggest that NF-κB plays critical roles in hepatocarcinogenesis. The aim of the present study is to characterize NF-κB activation and correlate it with the degree of malignancy in HCC. Methods: To examine the correlation between the positivity of the nuclear p50 subunit and HCC recurrence, we analyzed immunostaining of the NF-κB p50 subunit in two groups of HCC samples with known prognosis and Akt phosphorylation status: 49 patients showing early recurrence within 6months (group A) and 50 patients who were recurrence-free for at least for 3years (group B). Results: In group A, positive nuclear staining of p50 was shown in 18 cases (36.7%), whereas only one case (2.0%) in group B had positive nuclear staining of p50 (P=2.48839×10^-5). This suggests a positive relationship between nuclear p50 and early recurrence and advanced HCC in humans. The presence of phosphorylated Akt correlated with nuclear staining of p50 in HCCs in group A (R²=0.213, P<0.001). Conclusion: Our results indicate that nuclear staining of p50 was clearly associated with early recurrent HCC, and the Akt pathway might play a role in NF-κB activation in a subset of early recurrent HCC.