Molecular markers of endometrial carcinoma detected in uterine aspirates

Eva Colas, Cristina Perez, Silvia Cabrera, Nuria Pedrola, Marta Monge, Josep Castellvi, Fernando Eyzaguirre, Jesus Gregorio, Anna Ruiz, Marta Llaurado, Marina Rigau, Marta Garcia, Tugçe Ertekin, Melania Montes, Rafael Lopez-Lopez, Ramon Carreras, Jordi Xercavins, Alicia Ortega, Tamara Maes, Elisabet RosellAndreas Doll, Miguel Abal, Jaume Reventos, Antonio Gil-Moreno

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74 Citations (Scopus)

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. Copyright © 2011 UICC.
Original languageEnglish
Pages (from-to)2435-2444
JournalInternational Journal of Cancer
Volume129
Issue number10
DOIs
Publication statusPublished - 15 Nov 2011

Keywords

  • endometrial cancer
  • minimally invasive screening
  • molecular biomarkers
  • uterine aspirate

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