Thirty-seven (57.8%) of the 64 heterozygous patients had a tumor-specific p53 allele LOH, being two times more common in HCC tumors larger than 8 cm than in HCC tumors 2 cm or smaller.
This study was conducted to detect abnormal levels of several proto-oncogenes (c-jun, c-fos, c-H-ras) and of the p53 and the alpha-fetoprotein gene in the liver during cirrhosis, a pathological process which predisposes to the development of hepatocarcinoma.
The mutation of the p53 genes and polymorphism of the RB gene were present in 25.8% (8/31) and 12.9% (4/31) of the advanced tumours, respectively, but the mutation was not found in small HCC.
Despite its correlation with p53 mutation and the unfavorable outcome of HCC with p53 mutation, the CD24 mRNA expression did not correlate with tumor size, tumor invasiveness, or patient's prognosis.
Expression of p53ser246 in this line resulted in a growth advantage when compared with either a control vector (which contains a large p53 deletion) or with a different p53 mutant, val135, not found in hepatocellular carcinoma.
The results also support the notion that the p53 gene codon 249 mutation may have etiological implications involving HCC from various geographic areas.
A mutation in the tumor suppressor p53 gene resulting in an Arg-->Ser substitution in position 249 is found frequently in human hepatocellular carcinomas associated with hepatitis B infection and with aflatoxin exposure.
The p 53 protein produced by this recombinant virus was used to investigate p53 binding proteins in seventeen cell lines, including 10 derived from human hepatocellular carcinoma, four from other human cancers, and three from non-human primate tissues.
Circulating antibodies against p53 were found in 25% (20 of 80) of the sera from patients with hepatocellular carcinoma but not in various nonmalignant liver diseases.
The aim of the present study was to establish whether p53 positivity correlates with the presence of structural p53 gene abnormalities in European hepatocellular carcinoma.
Eight of the 12 patients with p53-positive HCC cells had p53 overexpression in the nontumorous hepatocytes within regenerative nodules adjacent to HCC tissue.
The relationship of EPHX to HCC varied by hepatitis B surface antigen status and indicated that a synergistic effect may exist. p53 codon 249 mutations were observed only among HCC patients with one or both high-risk genotypes.
Since p53 mutations occur in 29% of hepatocellular carcinomas worldwide, we tested the tumors for p53 mutations and serum samples for anti-p53 antibodies.
These data indicate that mutation and/or loss of heterozygosity in the p53 gene, independent of the 249 mutation, play a critical role in the development of hepatitis B virus-associated HCCs in China.
The p53 mRNA concentrations were remarkably reduced or undetectable in two hepatocellular carcinomas, whereas the two tumors (cases 2 and 3) that had single base changes at the acceptor site of intron 7 had both normal and abnormally sized p53 mRNAs.
To demonstrate the program, the mutational spectra of single base substitutions in the p53 gene are compared in (i) bladder cancers from smokers and non-smokers, (ii) small-cell lung cancers, non-small-cell lung cancers and colon cancers and (iii) hepatocellular carcinomas from high- and low-aflatoxin exposure groups. p53 mutations differ in several important aspects from a typical mutational spectra experiment, where a homogeneous population of cells is treated with a specific mutagen and mutations at a specific locus are recovered by phenotypic selection.
These data indicate that mutations of the p53 gene may be important in the development of human hepatocellular carcinoma and that, in contrast to other tumors, the mutations of the p53 gene in hepatocellular carcinomas can be clustered in a specific codon of the gene.