Mutation of TP53 gene is involved in carcinogenesis of hepatic undifferentiated (embryonal) sarcoma of the adult, in contrast with Wnt or telomerase pathways: an immunohistochemical study of three cases with genomic relation in two cases

J Hepatol. 2005 Mar;42(3):424-9. doi: 10.1016/j.jhep.2004.10.021.

Abstract

Background/aims: Hepatic undifferentiated (embryonal) sarcoma (HUS) is an exceptional hepatic malignant tumor in adults. Genetic studies were never reported in adult cases.

Methods: In this study concerning three cases of HUS occurring in adult, we studied the three classical ways of carcinogenesis i.e. the TP53 (p53), Wnt (CTNNB1/beta-catenin and AXIN1) and telomerase (hTERT) pathways. We studied the expression of p53, beta-catenin and telomerase catalytic subunit hTERT by immunohistochemistry in the three cases; we determined TP53 gene mutation in two cases and the genome-wide allelotype, AXIN1, and CTNNB1/beta-catenin gene mutation in one case.

Results: Immunohistochemistry showed an overexpression of p53 in more than 80% of tumoral cells; furthermore, mutations of TP53 were observed in two cases, involving the sequence-specific DNA binding domain. In contrast, no mutation was found in CTNNB1/beta-catenin and AXIN1 genes. Tumoral cells did not show hTERT staining nor nuclear expression of beta-catenin. In addition, allelotype analysis in one case showed loss of heterozygosity of chromosome 7p, 11p, 17p, 22q, and allelic imbalance of 1p, 8p, 20q.

Conclusions: In this report of HUS in three adult patients, we emphasize the role of TP53 pathway in carcinogenesis of this rare tumor. This point could be of interest for therapeutic strategies.

Publication types

  • Case Reports
  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Female
  • Genes, p53*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Liver Neoplasms / genetics*
  • Middle Aged
  • Mutation*
  • Pregnancy
  • Sarcoma / genetics*
  • Telomerase / genetics*
  • Wnt Proteins

Substances

  • Intercellular Signaling Peptides and Proteins
  • Wnt Proteins
  • Telomerase