title: Annexin-A2 as predictor biomarker of recurrent disease in endometrial cancer.
abstract: Endometrial carcinomas, the most common malignant tumour of the female genital tract, are usually diagnosed at an early stage with uterine-confined disease and an overall favourable prognosis. However, up to 20% of endometrial carcinomas will end up in recurrent disease, associated with a drop in survival and representing the major clinical challenge. Management of this group of risk patients relies on robust biomarkers that may predict which endometrial carcinomas will relapse. For this, we performed a proteomic analysis comparing primary lesions with recurrences and identified ANXA2 as a potential biomarker associated with recurrent disease that we further validated in an independent series of samples by immunohistochemistry. We demonstrated in vitro a role for ANXA2 in the promotion of metastasis rather than interfering with sensitivity to radio/chemotherapy. In addition, ANXA2 silencing resulted in a reduced metastatic pattern in a mice model of endometrial cancer dissemination, with a limited presence of circulating tumor cells. Finally, a retrospective study in a cohort of 93 patients showed that ANXA2 effectively predicted those endometrioid endometrial carcinomas that finally recurred. Importantly, ANXA2 demonstrated a predictive value also among low risk Stage I endometrioid endometrial carcinomas, highlighting the clinical utility of ANXA2 biomarker as predictor of recurrent disease in endometrial cancer. Retrospective and prospective studies are ongoing to validate ANXA2 as a potential tool for optimal stratification of patients susceptible to receive radical surgery and radio/chemotherapy.
authors.affiliation: Translational Medical Oncology, Health Research Institute of Santiago (IDIS), Fundacion Ramon Dominguez, SERGAS, Santiago de Compostela, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Alonso-Alconada
authors.forename: Maria
authors.initials: M
authors.lastname: Santacana
authors.forename: Pablo
authors.initials: P
authors.lastname: Garcia-Sanz
authors.forename: Laura
authors.initials: L
authors.lastname: Muinelo-Romay
authors.forename: Eva
authors.initials: E
authors.lastname: Colas
authors.forename: Cristina
authors.initials: C
authors.lastname: Mirantes
authors.forename: Marta
authors.initials: M
authors.lastname: Monge
authors.forename: Juan
authors.initials: J
authors.lastname: Cueva
authors.forename: Esther
authors.initials: E
authors.lastname: Oliva
authors.forename: Robert A
authors.initials: RA
authors.lastname: Soslow
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Lopez
authors.forename: Jose
authors.initials: J
authors.lastname: Palacios
authors.forename: Jaime
authors.initials: J
authors.lastname: Prat
authors.forename: Joan
authors.initials: J
authors.lastname: Valls
authors.forename: Camilla
authors.initials: C
authors.lastname: Krakstad
authors.forename: Helga
authors.initials: H
authors.lastname: Salvesen
authors.forename: Antonio
authors.initials: A
authors.lastname: Gil-Moreno
authors.forename: Rafael
authors.initials: R
authors.lastname: Lopez-Lopez
authors.forename: Xavier
authors.initials: X
authors.lastname: Dolcet
authors.forename: Gema
authors.initials: G
authors.lastname: Moreno-Bueno
authors.forename: Jaume
authors.initials: J
authors.lastname: Reventos
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
authors.forename: Miguel
authors.initials: M
authors.lastname: Abal
mesh_terms: D000368:Aged; D000818:Animals; D017306:Annexin A2 / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D016889:Endometrial Neoplasms / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000175:diagnosis; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000175:diagnosis*; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D012189:Retrospective Studies
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D014408:Biomarkers, Tumor
keywords: ANXA2; biomarker; endometrial cancer; metastasis; recurrent disease