title: Molecular markers of endometrial carcinoma detected in uterine aspirates.
abstract: Endometrial cancer (EC) is the most frequent of the invasive tumors of the female genital tract. Although usually detected in its initial stages, a 20% of the patients present with advanced disease. To date, no characterized molecular marker has been validated for the diagnosis of EC. In addition, new methods for prognosis and classification of EC are needed to combat this deadly disease. We thus aimed to identify new molecular markers of EC and to evaluate their validity on endometrial aspirates. Gene expression screening on 52 carcinoma samples and series of real-time quantitative PCR validation on 19 paired carcinomas and normal tissue samples and on 50 carcinoma and noncarcinoma uterine aspirates were performed to identify and validate potential biomarkers of EC. Candidate markers were further confirmed at the protein level by immunohistochemistry and Western blot. We identified ACAA1, AP1M2, CGN, DDR1, EPS8L2, FASTKD1, GMIP, IKBKE, P2RX4, P4HB, PHKG2, PPFIBP2, PPP1R16A, RASSF7, RNF183, SIRT6, TJP3, EFEMP2, SOCS2 and DCN as differentially expressed in ECs. Furthermore, the differential expression of these biomarkers in primary endometrial tumors is correlated to their expression level in corresponding uterine fluid samples. Finally, these biomarkers significantly identified EC with area under the receiver-operating-characteristic values ranging from 0.74 to 0.95 in uterine aspirates. Interestingly, analogous values were found among initial stages. We present the discovery of molecular biomarkers of EC and describe their utility in uterine aspirates. These findings represent the basis for the development of a highly sensitive and specific minimally invasive method for screening ECs.
authors.affiliation: Biomedical Research Unit, Research Institute Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Colas
authors.forename: Cristina
authors.initials: C
authors.lastname: Perez
authors.forename: Silvia
authors.initials: S
authors.lastname: Cabrera
authors.forename: Nuria
authors.initials: N
authors.lastname: Pedrola
authors.forename: Marta
authors.initials: M
authors.lastname: Monge
authors.forename: Josep
authors.initials: J
authors.lastname: Castellvi
authors.forename: Fernando
authors.initials: F
authors.lastname: Eyzaguirre
authors.forename: Jesus
authors.initials: J
authors.lastname: Gregorio
authors.forename: Anna
authors.initials: A
authors.lastname: Ruiz
authors.forename: Marta
authors.initials: M
authors.lastname: Llaurado
authors.forename: Marina
authors.initials: M
authors.lastname: Rigau
authors.forename: Marta
authors.initials: M
authors.lastname: Garcia
authors.forename: Tugçe
authors.initials: T
authors.lastname: Ertekin
authors.forename: Melania
authors.initials: M
authors.lastname: Montes
authors.forename: Rafael
authors.initials: R
authors.lastname: Lopez-Lopez
authors.forename: Ramon
authors.initials: R
authors.lastname: Carreras
authors.forename: Jordi
authors.initials: J
authors.lastname: Xercavins
authors.forename: Alicia
authors.initials: A
authors.lastname: Ortega
authors.forename: Tamara
authors.initials: T
authors.lastname: Maes
authors.forename: Elisabet
authors.initials: E
authors.lastname: Rosell
authors.forename: Andreas
authors.initials: A
authors.lastname: Doll
authors.forename: Miguel
authors.initials: M
authors.lastname: Abal
authors.forename: Jaume
authors.initials: J
authors.lastname: Reventos
authors.forename: Antonio
authors.initials: A
authors.lastname: Gil-Moreno
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001826:Body Fluids / Q000737:chemistry; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor