1. ¹Department of Pathology, National University Hospital, Yong Loo Lin Medical School, National University of Singapore (NUS), Singapore, Singapore
2. ²Oncology Research Institute, National University of Singapore (NUS), Singapore, Singapore
3. ³National Skin Centre, Singapore, Singapore
4. ⁴Institute of Molecular and Cell Biology, Singapore, Singapore

Correspondence: Professor Y Ito, Institute of Molecular and Cell Biology, 61 Biopolis Drive – Proteos, Singapore 138673, Singapore. E-mail: itoy@imcb.a-star.edu.sg

⁵These authors contributed equally to this work.

Received 31 March 2006; Accepted 8 May 2006; Published online 12 June 2006.

Abstract

Basal cell carcinomas (BCC), which are the most common form of skin malignancy, are invariably associated with the deregulation of the Sonic Hedgehog (Shh) signalling pathway. As such, BCC represent a unique model for the study of interactions of the Shh pathway with other genes and pathways. We constructed a tissue microarray (TMA) of 75 paired BCC and normal skin and analysed the expression of -catenin and RUNX3, nuclear effectors of the wingless-Int (Wnt) and bone morphogenetic protein/transforming growth factor- pathways, respectively. In line with previous reports, we observed varying subcellular expression pattern of -catenin in BCC, with 31 cases (41%) showing nuclear accumulation. In contrast, all the BCC cases tested by the TMA showed RUNX3 protein uniformly overexpressed in the nuclei of the cancer cells. Analysis by Western blotting and DNA sequencing indicates that the overexpressed protein is normal and full-length, containing no mutation in the coding region, implicating RUNX3 as an oncogene in certain human cancers. Our results indicate that although the deregulation of Wnt signalling could contribute to the pathogenesis of a subset of BCC, RUNX3 appears to be a universal downstream mediator of a constitutively active Shh pathway in BCC.