Sporadic childhood hepatoblastomas show activation of β-catenin, mismatch repair defects and p53 mutations

Maria C. Curia, Michele Zuckermann, Laura De Lellis, Teresa Catalano, Rossano Lattanzio, Gitana Aceto, Serena Veschi, Alessandro Cama, Jean Bernard Otte, Mauro Piantelli, Renato Mariani-Costantini, Francesco Cetta, Pasquale Battista

Research output: Contribution to journalArticlepeer-review

Abstract

Hepatoblastoma, a rare embryonic tumor that may arise sporadically or in the context of hereditary syndromes (familial adenomatous polyposis and Beckwith-Wiedemann's) is the most frequent liver cancer of childhood. Deregulation of the APC/β-catenin pathway occurs in a consistent fraction of hepatoblastomas, with mutations in the APC and β-catenin genes implicated in familial adenomatous polyposis-associated and sporadic hepatoblastomas, respectively. Alterations in other cancer-related molecular pathways have not been reported. We investigated a series of 21 sporadic paraffin-embedded hepatoblastoma cases for mutations in the p53 (exons 5-8) and β-catenin (exon 3) genes, loss of heterozygosity at APC, microsatellite instability and immunohistochemical expression of β-catenin and of the two main mismatch repair proteins, MLH1 and MSH2. No loss of heterozygosity at APC was detected. We found mutations in β-catenin and p53 in 4/21 (19%) and 5/21 (24%) cases respectively, β-catenin protein accumulation in 14/21 cases (67%), microsatellite instability in 17/21 cases (81%), of which eight resulted positive for high-level of microsatellite instability (in four cases associated with loss of MLH1/MSH2 immunostaining). No correlations between involved molecular pathway(s) and hepatoblastoma histotype(s) emerged. This study confirms that β-catenin deregulation is involved in sporadic hepatoblastoma and also suggests that mismatch repair defects and p53 mutations contribute to this rare liver cancer. Sporadic hepatoblastoma appears to be molecularly and phenotypically heterogeneous and may reflect different pathways of liver carcinogenesis.

Original languageEnglish
Pages (from-to)7-14
Number of pages8
JournalModern Pathology
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 2008

Keywords

  • β-catenin
  • Hepatoblastoma
  • Immunohistochemistry
  • Microsatellite instability
  • Mutations
  • p53

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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