Assessment of the proliferative marker Ki-67 and p53 Protein Expression in HBV-and HCV related-related hepatocelular carcinoma cases in Egypt

ABSTRACT

Chronic HBV and HCV infections are the major risk factors for the development of HCC through a multistep pathway that involves viral and non-viral dependent pathophysiological steps. Hepatic expression of the nuclear proliferative marker ki-67 and the p53 oncoprotein were found to be associated with poor outcome. So, the present study was done to evaluate the changes in expression of Ki-67 and p53 oncoprotein, and to determine p53 gene mutation in HBV/HCV-related HCC Egyptian patients. Eight HBV-and 22 HCV-positive HCC cases have been examined for the presence of p53 mutation by immunohistochemistry [IHC] and single-strand conformation polymorphism [SSCP], followed by direct DNA sequencing. HCV were genotyped by LiPA-II. Our results have shown that the proliferative marker ki-67 LI and p53 were highly expressed and significantly related to tumor grade in the Egyptian HCC cases [p < 0.05]. Also, p53 mutation was found in 16 HCC cases by IHC and in 14 HCC cases by SSCP, only 11 patients showed p53 mutation by sequencing. The highest mutation rate was scored for exon 7 [7 mutations] at codon 249; 4 out of 8 [50%] of HBV-related HCC cases and 3 out of 22 [13.6%] of HCV-related HCC cases, followed by exon 5 [3 mutations] at codons 133, 146, 176 in HCV-related HCC cases, then exon 8 at codon 275 in HCV-related HCC cases. The concordance between the IHC and sequencing analysis was 69%.The present study demonstrates the association between the proliferative marker ki-67 and p53 expression with the tumor grade of Egyptian HBV/HCV-related HCC cases. Our results also support the hypothesis that p53 mutations are rather a late event in the carcinogenesis. Also, they suggest that the final steps of hepatocarcinogenesis are common and independent of the aetiology of the viral infection