Comparison of p53 and prohibitin expression in the spectrum of hepatitis, cirrhosis, and hepatocellular carcinoma

Abstract

Aim: To investigate the correlation of p53 and prohibitin (PHB) expression in the spectrum of hepatitis, cirrhosis, and human hepatocellular carcinoma (HCC).

Methods: Hepatic biopsies from patients with HCC (n = 60), cirrhosis (CIR, n = 30), hepatitis C virus (HCV, n = 30), and normal livers (NL, n = 20) were examined for immunohistochemical expression of RelA/p65, tumor necrosis factor receptor-1 (TNFR1), TNF-related apoptosis-inducing ligand (TRAIL), p53, and PHB. The samples were also analysed by nuclear factor kappa B (NFκB) Southwestern histochemistry and a transferase-mediated dUTP-biotin nick-end labelling assay.

Results: Expression of NFκB and RelA/p65 was detected increasingly from NL to CIR, but had a diminished labelling in the HCC cases (P < 0.05). Expression levels of TNFR1 and TRAIL followed the same pattern (P < 0.05). Apoptosis was increased in HCC, but was progressively reduced from CIR to NL (P < 0.05). p53 and PHB nuclear expressions were amplified in cases of HCC, but diminished in NL, HCV, and CIR (P < 0.05).

Conclusion: These results suggest that in addition to well-understood sequences of proinflammatory events such as TNF-induced NFκB activation and NFκB/TRAIL pathway-mediated apoptosis, development of HCC is also influenced by regulation of p53 and PHB tumour suppressor function. Additional studies are necessary to explain the contradictory mechanisms of the tumour microenvironment observed in the sequence of HCV, CIR, and HCC.

Keywords

p53 / prohibitin / nuclear factor kappa B / apoptosis / hepatocellular carcinoma

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