TFF3 is a member of the trefoil family of stable secretory proteins found in gastrointestinal mucosa. TFF3 may function to protect the mucosa from insults and stabilize the mucus layer and it is also involved in epithelial healing. In immunohistochemistry, it is useful as a marker for columnar epithelium and has utility in the diagnosis of a number of cancers where it is often deregulated. TFF3 sees upregulation in prostate, stomach and breast cancer and downregulation in thyroid carcinomas. It may be used to distinguish breast from ovarian serous carcinoma in cancers of uncertain origin. In normal tissue, TFF3 is expressed in goblet cells of the intestines and colon, has secretory positivity in the thyroid gland, and stains mucus secreting cells in the cervix uteri and respiratory epithelia. References: Arch Otolaryngol Head Neck Surg. 2009;135(6):590-596, DOI: 10.1001/archotol.128.1.29; Archives of Pathology & Laboratory Medicine. 2014 Dec. 138(12):1583-1610, DOI: 10.5858/arpa.2014-0061-RA