p53 Mutation in HCV-genotype-4 associated hepatocellular carcinoma in Egyptian patients

ABSTRACT

HCV-associated hepatocellular carcinoma [HCC] is a common neoplasm in Egypt where genotype-4 is prevalent. In the present study the incidence and pattern of p53 mutations was assessed in relation to HCV-genotype-4 in Egyptian HCC patients. We investigated 25 HCV positive HCCs for p53 mutations over expression in relation to HCV-N53 by immunohistochemistry, SSCP and sequencing. Genotyping was done using LiPA-Il and TRUGENE 5 NC sequencing kit. Results were correlated to standard clinicopathologic prognostic factors for HCC. Thirteen cases showed p53 overexpression, and 10 showed p53 mutation [13 mutations] by sequencing [72% concordance]. The highest mutation rate was in exons 6 and 7 [30%] followed by exons 5 and 8 [20%]. Mutations included 3 transitions, 5 transversions, 3 deletions, and 2 insertions. All exon 7 mutations were at codon 249 specific for AFB1 [AGG-AGT, Arg-Ser] and codon 248 specific for vinyl chloride contamination [CGG-TGG, Arg-Trp]. Other mutations reported are novel. Immunostaining for HCV N53 was detected in 19 cases independent of p53 mutation. p53 aberrations were significantly associated with poor prognostic factors for HCC. However, no specific pattern for p53 mutations was observed in HCV genotype 4-associated HCC and no significant relation between p53 mutations, HCV-N53 expressions or any HCV sub-genotype-4 sequence