%0 Journal Article %A Aoife J McCarthy %A Runjan Chetty %T Smad4/DPC4 %D 2018 %R 10.1136/jclinpath-2018-205095 %J Journal of Clinical Pathology %P jclinpath-2018-205095 %X 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. %U https://jcp.bmj.com/content/jclinpath/early/2018/05/02/jclinpath-2018-205095.full.pdf