Abstract
Forty-two patients with hepatocellular carcinoma (HCC) were resected and their tumours were analysed for p53 mutations by GC-clamped denaturing gradient gel electrophoresis (DGGE), single-strand conformation polymorphism (SSCP) and gene sequencing. All the exons have been analysed in this study. Eight of 12 HCCs with cirrhosis due to viral hepatitis and the two patients with sarcomatoid changes displayed p53 mutations. In contrast, no mutation was observed in the fibrolamellar variant (n = 9), non-cirrhotics (n = 13) and alcoholic cirrhosis (n = 6). The mutations observed were in exons 5-8. Two mutations were observed in codons 136 and 213 as well as a T insertion between residues 156 and 157 (exon 5) and these are reported for the first time in HCC. Likewise, the silent mutation polymorphism in codon 213 was noticed in 3 of the 42 patients. Survival analysis of these patients after surgery showed the mean and median survival in patients with wild-type p53 to be 60 and 43 months respectively. In the group with p53 mutations, the mean and median survival was 15 and 12 months. The difference was statistically significant (P= 0.003).
Highlights
P53 protein is a DNA-binding, cell-regulating transcription factor that has multiple critical roles in the complex pathway governing cell cycle and in the balance between cell division and apoptosis
We examined 42 primary liver carcinoma specimens, which were surgically resected at the Hammersmith Hospital (UK) with histologically confirmed diagnosis, for mutation of the p53 gene by denaturing gradient gel electrophoresis (DGGE), single-strand conformation polymorphism (SSCP) and sequence analysis
DGGE analysis of exon 6 of four patients showed in the tumoral samples a complex deviated pattern compared with the control (Figure 2)
Summary
We aimed to find out whether p53 mutation could influence survival after surgical resection in these patients
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