HCC is the main primary liver tumor, accounting for 85–90% of primary liver cancers diagnosed. In Egypt, HCC contributes about 8% of all cancers, ranking the second in males and the sixth in females.
TP53 gene encodes the p53 protein which plays a golden role in the DNA damage response network, including cell cycle arrest, apoptosis, DNA repair and cellular senescence. TP53 loss of function mutations or allelic deletions in chromosome 17p are commonly associated with human carcinogenesis.
Silent mating type information regulation 2 homolog1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase and has been studied widely as a factor in human disease. The role of SIRT1 in cancer is still in controversy, it could act as both tumor suppressor or tumor promoter. This may depend on its targets or the cellular location or specific cancers.
This is a retrospective study which is conducted on 60 cases of formalin fixed biopsy specimens. The studied cases were 33 of HCC, 12 of chronic viral hepatitis C, 15 of cirrhosis and 6 cases of apperantly normal liver tissue.
Mean age of studied HCC cases was 53.5 years with male to female ratio of 5:1.
Histopathological examination was done for each case of HCC to assess the histopathological type, the grade and the presence of vascular invasion. For chronic viral hepatitis C cases we assess the stage of fibrosis and hepatitis activity.
Avidin Biotin complex technique using anti-P53 and anti-SIRT1was applied for each case, and examined to assess their expression. Correlations between P53 as well as SIRT1 expression and different clinicopathological variables were done.
Each case was staged according to TNM staging system and there was a statistically positive correlation between TNM stage and grades of studied HCC cases. Free 2 year survival were detected in 6 (27.3%) cases out of 33 HCC cases while 24 (72.7%) cases showed recurrent/dead with significant statistical correlation with tumor grade, TNM stage and presence of vascular invasion.
None of apparently normal liver tissue showed neither P53 nor SIRT1 expression. However its expression increased gradually in progression throughout chronic viral hepatitis C and cirrhosis to be the highest in HCC suggesting a possible role of them in the hepatic carcinogenesis.
There were statistically significant positive correlation between P53expression and tumor grade, TNM stage, 2 years survival and presence of both vascular invasion and underlying cirrhosis.
No relation was demonstrated between SIRT1expression and neither histologic type nor presence of vascular invasion. While there were statistically significant positive correlations between its expression and tumor grade, TNM stage, free 2 year survival and presence of underlying cirrhosis.
There was statistically significant correlation between P53 expression and SIRT1 expression. Which revealed a possible link between them.
|