title: Trefoil factor 3: a novel serum marker identified by gene expression profiling in high-grade endometrial carcinomas.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bignotti
authors.forename: A
authors.initials: A
authors.lastname: Ravaggi
authors.forename: R A
authors.initials: RA
authors.lastname: Tassi
authors.forename: S
authors.initials: S
authors.lastname: Calza
authors.forename: E
authors.initials: E
authors.lastname: Rossi
authors.forename: M
authors.initials: M
authors.lastname: Falchetti
authors.forename: C
authors.initials: C
authors.lastname: Romani
authors.forename: E
authors.initials: E
authors.lastname: Bandiera
authors.forename: F E
authors.initials: FE
authors.lastname: Odicino
authors.forename: S
authors.initials: S
authors.lastname: Pecorelli
authors.forename: A D
authors.initials: AD
authors.lastname: Santin
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D018394:CA-125 Antigen / Q000097:blood; D016000:Cluster Analysis; D016889:Endometrial Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D010455:Peptides / Q000097:blood* / Q000235:genetics; D000071165:Trefoil Factor-3
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D010455:Peptides; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3