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  1. Aoife J McCarthy,
  2. Runjan Chetty
  1. Laboratory Medicine Program, Department of Anatomical Pathology, University Health Network and University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Professor Runjan Chetty, Department of Anatomical Pathology, Laboratory Medicine Program, University Health Network, Toronto General Hospital, Toronto, ON M5G 2C4, Canada; runjan.chetty{at}


Smad4 or DPC4 belongs to a family of signal transduction proteins that are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor beta (TGF-β) signaling via several pathways. The gene acts as a tumour suppressor gene and inactivation of smad4/DPC4 is best recognised in pancreatic cancer. However, smad4/DPC4 is also mutated in other conditions and cancers such as juvenile polyposis syndrome with and without hereditary haemorrhagic telangiectasia, colorectal and prostate cancers.

Immunohistochemistry for smad4/DPC4 protein is most useful in separating benign/reactive conditions from pancreatic cancer in needle/core biopsies. In normal and reactive states, the protein is localised to the cytoplasm and nucleus, while the protein is lost in high-grade pancreatic intraepithelial neoplasia/carcinoma in situ and pancreatic cancer.

  • smad4
  • DPC
  • tumour suppressor gene
  • TGF-β
  • pancreatic cancer

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  • Handling editor Tahir S Pillay.

  • Contributors Both authors contributed equally.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.