Laboratory Medicine Program, Department of Anatomical Pathology, University Health Network and University of Toronto, Toronto, Ontario, Canada.
J Clin Pathol. 2018 Aug;71(8):661-664. doi: 10.1136/jclinpath-2018-205095. Epub 2018 May 2.
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 is best recognised in pancreatic cancer. However, 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 或 DPC4 属于信号转导蛋白家族，可被跨膜丝氨酸-苏氨酸受体激酶磷酸化和激活，从而响应转化生长因子β（TGF-β）信号，通过多种途径进行信号传递。该基因作为一种肿瘤抑制基因失活，在胰腺癌中最易被识别。然而，在其他情况下，如伴有或不伴有遗传性出血性毛细血管扩张症的青少年息肉病综合征、结直肠癌和前列腺癌， 也会发生突变。Smad4/DPC4 蛋白的免疫组织化学在区分针芯活检中的良性/反应性病变与胰腺癌方面最有用。在正常和反应状态下，该蛋白定位于细胞质和细胞核，而在高级别胰腺上皮内瘤变/原位癌和胰腺癌中则丢失。
