Allelotype and Loss of Heterozygosity of P53 in Primary and Recurrent Hepatocellular Carcinomas. A Study of 150 Patients

Background: The allelotype and loss of heterozygosity (LOH) of the p53 gene in human hepatocellular carcinoma (HCC) were studied in 150 patients with resected primary HCC and 18 with recurrent HCC.

Methods: DNA samples of paired HCC and livers were cut with BanII enzyme for the study of p53 allelotype and allele loss. The medical records of the patients were carefully reviewed.

Results: Sixty-four (42.7%) patients were heterozygous for the p53 gene, 69 (46%) were homozygous for the 1.5/1.4 kb small (S) allele, and 17 (11.3%) were homozygous for the 2.9 kb large (L) allele. The frequencies of the minor L allele (0.323) and of the major S allele (0.677) in this population of Chinese patients differed from the frequencies previously reported for North American Caucasians (0.13 and 0.87, respectively). The heterozygous patients tended to have lower serum hepatitis B surface- and e antigens (HBsAg and HBeAg) and higher diabetes mellitus (DM) than did homozygous patients (SS and LL). 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. The frequency of DM was four times higher in the heterozygous patients who had p53 LOH than in those who retained both alleles. LOH of p53 did not correlate with tumor invasiveness or differentiation, hepatitis B or C virus infection, or prognosis.

Conclusion: The allelotype of p53 gene in HCC correlates with HBsAg and HBeAg seropositivities and DM. LOH of the p53 gene is a common event in HCC, correlates with DM, and occurs less often in familial HCC. LOH can identify the clonal origin of recurrent HCC but is not a critical prognostic factor.