Molecular markers of endometrial carcinoma detected in uterine aspirates

• Published in: International journal of cancer Vol. 129; no. 10; pp. 2435 - 2444
• Main Authors: Colas, Eva, Perez, Cristina, Cabrera, Silvia, Pedrola, Nuria, Monge, Marta, Castellvi, Josep, Eyzaguirre, Fernando, Gregorio, Jesus, Ruiz, Anna, Llaurado, Marta, Rigau, Marina, Garcia, Marta, Ertekin, Tugçe, Montes, Melania, Lopez‐Lopez, Rafael, Carreras, Ramon, Xercavins, Jordi, Ortega, Alicia, Maes, Tamara, Rosell, Elisabet, Doll, Andreas, Abal, Miguel, Reventos, Jaume, Gil‐Moreno, Antonio
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.11.2011; Wiley-Blackwell
• Subjects: Biological and medical sciences; Biomarkers, Tumor - analysis; Body Fluids - chemistry; endometrial cancer; Endometrial Neoplasms - genetics; Endometrial Neoplasms - metabolism; Female; Female genital diseases; Gene Expression Profiling; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; minimally invasive screening; molecular biomarkers; Reproducibility of Results; Tumors; uterine aspirate; Endometrium cancer; Genetic marker; uterine aspirate; Uterus cancer; Biological marker; minimally invasive screening; molecular biomarkers; Malignant tumor; Molecular marker; Medical screening; Female genital diseases; Uterus carcinoma; Cancerology; Uterine diseases; endometrial cancer; Endometrium carcinoma; Cancer
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.25901

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.