TY - JOUR
T1 - Molecular markers of endometrial carcinoma detected in uterine aspirates
AU - Colas, Eva
AU - Perez, Cristina
AU - Cabrera, Silvia
AU - Pedrola, Nuria
AU - Monge, Marta
AU - Castellvi, Josep
AU - Eyzaguirre, Fernando
AU - Gregorio, Jesus
AU - Ruiz, Anna
AU - Llaurado, Marta
AU - Rigau, Marina
AU - Garcia, Marta
AU - Ertekin, Tugçe
AU - Montes, Melania
AU - Lopez-Lopez, Rafael
AU - Carreras, Ramon
AU - Xercavins, Jordi
AU - Ortega, Alicia
AU - Maes, Tamara
AU - Rosell, Elisabet
AU - Doll, Andreas
AU - Abal, Miguel
AU - Reventos, Jaume
AU - Gil-Moreno, Antonio
PY - 2011/11/15
Y1 - 2011/11/15
N2 - 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.
AB - 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.
KW - endometrial cancer
KW - minimally invasive screening
KW - molecular biomarkers
KW - uterine aspirate
U2 - 10.1002/ijc.25901
DO - 10.1002/ijc.25901
M3 - Article
SN - 0020-7136
VL - 129
SP - 2435
EP - 2444
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 10
ER -