ABSTRACT
Background: 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
Materials and Methods: 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
Results: 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%
Conclusion: 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
ABSTRACT
Background: Human polyomaviruses JCV and BKV can cause several clinical manifestations in immunocompromised hosts, including progressive multifocal leukoencephalopathy [PML] and hemorrhagic cystitis. The association of these viruses with clinical tumors and their possible roles in the etiology of nonhodgkin's lymphoma are not clear. So, the purpose of this study was to screen for the presence of JCV, and BKV DNA sequences in NHL, where immunocompromised individuals are known to be at risk of development of virus-mediated neoplasm
Materials and Methods: Fresh tumor samples from 66 Egyptian patients with Non-Hodgkin's lymphoma and 34 control groups were examined by polymerase chain reaction [PCR] for detection of JCV DNA and BKV DNA sequences
Results: Our results have shown that JCV DNA sequences were found in the tumor tissues of 40/66 [60%] NHL patients compared to 14/34 [41.1%] of the control group, whereas BKV DNA sequences were found in 23/66 [34.8%] of NHL patients compared to 7/34 [20.5%] of the control group. There was no statistically significant difference between the presence of virus in cases and controls [p > 0.05]. For overall survival [OS] on univariate analysis, negative JCV DNA patients had not a different time to survive compared with positive JCV DNA patients [Log Rank test = 1.62; p = 0.20]. Also, Presence of JCV DNA sequences in NHL patients did not affect the response of those patients to chemotherapy [Log Rank test = 0.74; p = 0.40]. The same findings were found with BKV infection where BKV had not any effect on the survival [Log Rank test=015; p = 0.70] and the response of those patients [Log rank test = 0.39; p = 0.53]
Conclusion: The present study has shown that presence of both BKV DNA and JCV DNA sequences in NHL patients had not any effect on overall survival [OS] or the response to chemotherapy in those patients