Trefoil factor 3: a novel serum marker identified by gene expression profiling in high-grade endometrial carcinomas

Br J Cancer. 2008 Sep 2;99(5):768-73. doi: 10.1038/sj.bjc.6604546.


This study identifies the genetic fingerprint of poorly differentiated endometrioid endometrial carcinomas (G3-EEC) and analyses the potential utility of trefoil factor 3 (TFF3) as novel serum marker in G3-EEC. Affymetrix microarrays were used to identify the gene expression patterns of 19 snap-frozen G3-EEC and 15 normal endometrium (NE) biopsies. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry were used to validate TFF3 expression. Finally, TFF3 serum levels were determined by ELISA in 25 G3-EEC patients, 42 healthy controls, and in 13 endometrial hyperplasia patients. Hierarchical cluster analysis showed TFF3 as the top differentially expressed gene between 363 upregulated genes in G3-EEC, when compared with NE. Trefoil factor 3 gene expression levels analysed by qRT-PCR significantly correlated with Affymetrix results (P<0.001; rs=0.85). By immunohistochemistry, TFF3 protein was significatively more expressed in EEC compared with NE (P<0.01), with cytoplasmatic positivity in 79% G3-EEC and 18% NE. Patients harbouring G3-EECs had significantly higher TFF3 serum concentration by ELISA when compared with healthy patients (P<0.001) or patients harbouring endometrial hyperplasia (P=0.012). In conclusion, TFF3 is highly expressed at gene and protein level in G3-EEC. Further investigations on a wider set of samples are warranted to validate TFF3 as a novel serum marker for early detection and/or monitoring of G3-EEC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • CA-125 Antigen / blood
  • Cluster Analysis
  • Endometrial Neoplasms / blood
  • Endometrial Neoplasms / diagnosis*
  • Endometrial Neoplasms / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Profiling*
  • Humans
  • Immunohistochemistry
  • Peptides / blood*
  • Peptides / genetics
  • Trefoil Factor-3


  • Biomarkers, Tumor
  • CA-125 Antigen
  • Peptides
  • TFF3 protein, human
  • Trefoil Factor-3