Expression of wild p53, mutated p53 and hypoxia inducible factor-1 alpha in hepatocellular carcinoma

ABSTRACT

To investigate the expression of wild p53, mutated p53 and hypoxia inducible factor-1 alpha [HIF-1 alpha] genes in hepatocellular carcinoma and correlate their expression with clinicopathological data. Liver biopsy samples of 30 hepatocellular carcinoma [HCC] subjects. 20 chronic hepatitis C [CHC] and 20 liver biopsy samples from non cancerous tissue [i.e control samples] of HCC were assessed by polymerase chain reaction [RT-PCR] and restriction enzyme analysis for the three genes; wild p53 gene, mutations in p53 at codon 249, exon 7 and hypoxia inducible factor-1 alpha gene. Wild p53 gene was detected in 18/30cases of HCC [60%], 16/20 cases of CHC [80%] and 15/20 cases of control samples [75%] with no significant difference between the studied groups. Mutated p53 gene was detected in 12/30 cases of HCC [40%], 4/20 cases of CHC [20%] and 5/20 cases of control samples [25%], also with no statistically significant difference between the studied groups while HIF-lalpha gene was expressed in 20/30 cases of HCC [66.7%] in comparison to 2/20 cases of CHC [10%] and 3/20 of control samples [15%] with a highly statistically significant difference [p<0.001]. The expression of both wild p53 and the mutated p53 correlated with tumor size but did not correlate with grade of malignancy nor serum alpha fetoprotein level, while the expression of HIF-1 alpha correlated with grade of malignancy and alpha fetoprotein level but not with tumor size. No correlation between expression of all genes and capsule infiltration or presence of cirrhosis was found in all groups. HIF-1 alpha is highly expressed in HCC and is related to grade of malignancy and serum alpha fetoprotein level