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Br J Dermatol. 2004 Jul;151(1):157-64.

Nuclear beta-catenin in basal cell carcinoma correlates with increased proliferation.

Author information

  • 1Department of Cancer Studies and Molecular Medicine, University of Leicester, UK. gss4@le.ac.uk

Abstract

BACKGROUND:

Virtually all BCCs have deregulation of the Hedgehog (Hh) signalling pathway and a proportion show nuclear beta-catenin accumulation. The latter is thought to be due to Hh pathway-directed Wnt expression but this has not been tested. An alternative cause of nuclear beta-catenin accumulation is gene mutation, which stabilizes the protein. Theoretically, reduced E-cadherin expression could also be important because it can sequester beta-catenin at the cell membrane. In turn, nuclear beta-catenin can increase expression of MYC and cyclin D1, thus potentially altering proliferation.

OBJECTIVES:

To assess whether nuclear beta-catenin occurs in BCC, and to look at potential causes and consequences.

METHODS:

Nuclear beta-catenin was assessed by immunohistochemistry, and its causes by analysis of E-cadherin expression, beta-catenin exon 3 mutation and WNT5A expression. Its consequences were assessed by analysing proliferation.

RESULTS:

We found nuclear beta-catenin in 20 of 86 paraffin-embedded sections of BCCs using immunohistochemistry. BCCs showed increased WNT5A relative to the surrounding skin. No mutations in exon 3 of the beta-catenin gene were found in 10 cases. There was no association between beta-catenin localization and E-cadherin expression. Tumours with nuclear beta-catenin had significantly higher proliferation (P < 0.01).

CONCLUSIONS:

The absence of beta-catenin gene mutations indicate that the Hh pathway-directed Wnt signalling remains the most likely cause of nuclear beta-catenin accumulation in BCC. Additionally, the correlation with increased proliferation is the first evidence that nuclear beta-catenin may have a biological effect. However, a causal link between Hh pathway deregulation, Wnt ligand overexpression, nuclear beta-catenin accumulation and increased proliferation remains to be confirmed.

PMID:
15270885
[PubMed - indexed for MEDLINE]
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