249 TP53 mutation has high prevalence and is correlated with larger and poorly differentiated HCC in Brazilian patients

BACKGROUND: Ser-249 TP53 mutation (249(Ser)) is a molecular evidence for aflatoxin-related carcinogenesis in Hepatocellular Carcinoma (HCC) and it is frequent in some African and Asian regions, but it is unusual in Western countries. HBV has been claimed to add a synergic effect on genesis of this particular mutation with aflatoxin. The aim of this study was to investigate the frequency of 249(Ser )mutation in HCC from patients in Brazil. METHODS: We studied 74 HCC formalin fixed paraffin blocks samples of patients whom underwent surgical resection in Brazil. 249(Ser )mutation was analyzed by RFLP and DNA sequencing. HBV DNA presence was determined by Real-Time PCR. RESULTS: 249(Ser )mutation was found in 21/74 (28%) samples while HBV DNA was detected in 13/74 (16%). 249(Ser )mutation was detected in 21/74 samples by RFLP assay, of which 14 were confirmed by 249(Ser )mutant-specific PCR, and 12 by nucleic acid sequencing. All HCC cases with p53-249ser mutation displayed also wild-type p53 sequences. Poorly differentiated HCC was more likely to have 249(Ser )mutation (OR = 2.415, 95% CI = 1.001 – 5.824, p = 0.05). The mean size of 249(Ser )HCC tumor was 9.4 cm versus 5.5 cm on wild type HCC (p = 0.012). HBV DNA detection was not related to 249(Ser )mutation. CONCLUSION: Our results indicate that 249(Ser )mutation is a HCC important factor of carcinogenesis in Brazil and it is associated to large and poorly differentiated tumors.