Diagnostic and prognostic impact of β-catenin alterations in pediatric liver tumors

  • Authors:
    • Hiroaki Yamaoka
    • Kazuhiro Ohtsu
    • Taijiro Sueda
    • Takashi Yokoyama
    • Eiso Hiyama
  • View Affiliations

  • Published online on: March 1, 2006     https://doi.org/10.3892/or.15.3.551
  • Pages: 551-556
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Abstract

Hepatoblastoma (HBL), a major childhood malignant neoplasm, represents the most frequent malignant liver tumor in childhood. Recent reports have shown the CTNNB1 coding β-catenin protein to be frequently mutated or deleted at hot-spot regions involving exon 3 in HBL. We investigated the genetic alterations of the CTNNB1 coding β-catenin protein and expression of several genes downstream of Wnt signals in 4 benign and 17 malignant pediatric liver tumors (PLTs) consisting of 15 HBL, 1 hepatocellular carcinoma, and 1 hepatic immature sarcoma. Of 17 malignant PLTs, 10 (56%) revealed pathogenic alterations of the CTNNB1 gene, including 4 with missense mutations at codons 28, 32, 34 or 44, and 6 with interstitial deletions that partially or totally affected exon 3. All 6 deletions were in-frame deletions without a frame shift. The high frequency without any correlation to histological type indicates that the CTNNB1 gene alteration is a crucial event in the tumorigenesis of malignant PLTs. The immunohistochemical studies in 17 malignant PLTs demonstrated the nuclear/cytoplasmic accumulation of β-catenin to be positive in all tumor specimens except for one hepatic sarcoma. A histological examination revealed all HBL cases involving tumors without detectable CTNNB1 gene alterations to show high expression of β-catenin, thus indicating the accumulation of β-catenin to be a common event in malignant PLTs, including HBL and hepatocellular carcinoma. Among the Wnt signal genes downstream of β-catenin, E-cadherin is expressed in all malignant PLTs, while cyclin D1 expression was significantly detected in malignant PLTs with an advanced stage of disease. An immunohistological examination of nuclear accumulation of β-catenin may thus be useful for diagnosing malignant PLTs. On the other hand, the expression of cyclin D1, a gene downstream of β-catenin, might play a role in tumor progression.

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March 2006
Volume 15 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yamaoka H, Ohtsu K, Sueda T, Yokoyama T and Hiyama E: Diagnostic and prognostic impact of β-catenin alterations in pediatric liver tumors. Oncol Rep 15: 551-556, 2006
APA
Yamaoka, H., Ohtsu, K., Sueda, T., Yokoyama, T., & Hiyama, E. (2006). Diagnostic and prognostic impact of β-catenin alterations in pediatric liver tumors. Oncology Reports, 15, 551-556. https://doi.org/10.3892/or.15.3.551
MLA
Yamaoka, H., Ohtsu, K., Sueda, T., Yokoyama, T., Hiyama, E."Diagnostic and prognostic impact of β-catenin alterations in pediatric liver tumors". Oncology Reports 15.3 (2006): 551-556.
Chicago
Yamaoka, H., Ohtsu, K., Sueda, T., Yokoyama, T., Hiyama, E."Diagnostic and prognostic impact of β-catenin alterations in pediatric liver tumors". Oncology Reports 15, no. 3 (2006): 551-556. https://doi.org/10.3892/or.15.3.551