Trefoil factor 3: a novel serum marker identified by gene expression profiling in high-grade endometrial carcinomas.
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.
Bignotti
E
E
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Ravaggi
A
A
Tassi
R A
RA
Calza
S
S
Rossi
E
E
Falchetti
M
M
Romani
C
C
Bandiera
E
E
Odicino
F E
FE
Pecorelli
S
S
Santin
A D
AD
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
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D010455:Peptides; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3