Trefoil factor 3 is a protein that in humans is encoded by the TFF3 gene. Members of the trefoil family are characterized by having at least one copy of the trefoil motif, a 40-amino acid domain that contains three conserved disulfide bonds. They are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are not defined, but they may protect the mucosa from insults, stabilize the mucus layer and affect healing of the epithelium. This gene is a marker of columnar epithelium and is expressed in a variety of tissues including goblet cells of the intestines and colon.

Using TFF3 as a marker of columnar epithelium, a process using an ingestible oesophageal sampling device (Cytosponge) coupled with immunocytochemistry for trefoil factor 3 to improve the accuracy and acceptability of the detection/screening of Barrett’s oesophagus has been developed. However the clinical utility of such a test may be limited by frequent staining of TFF3 in gastric cardia and subsequent risk of false positives.