title: Up-regulation of ERM/ETV5 correlates with the degree of myometrial infiltration in endometrioid endometrial carcinoma.
abstract: To elucidate alterations in gene expression in endometrioid endometrial carcinoma (EEC), differential gene expression profiling was previously described in both tumour and non-tumour contexts, and the up-regulation of the RUNX1/AML1 proto-oncogene in EEC was characterized. Among the set of genes found to be up-regulated significantly in EEC, the most relevant, ERM/ETV5, corresponds to the PEA3 subfamily and is a member of the Ets family of transcription factors that contain the Ets DNA-binding domain and are involved in matrix remodelling. In the present work, an attempt was made to characterize the expression of ERM/ETV5 in EEC throughout the process of tumourigenesis. Gene expression levels of ERM/ETV5 were quantified by real-time quantitative PCR (RT-Q-PCR) using a large panel of samples ranging from non-invasive IA to metastatic IIIA stages, and protein expression was characterized by tissue array immunohistochemistry (TMA). RT-Q-PCR validated ERM/ETV5 up-regulation in EEC and demonstrated a specific and significant increase restricted to those tumour stages associated with myometrial invasion. TMA showed that ERM/ETV5 up-regulation correlated mainly with the transition from atrophic endometrium to hyperplasia and carcinoma during tumour progression. Furthermore, ERM/ETV5 gene and protein expression levels were associated with low tumour grade. Finally, ERM/ETV5 up-regulation correlated with that of RUNX1/AML1. All of these results lead to the proposal of a co-operative role between ERM/ETV5 and RUNX1/AML1 during the early events of endometrial tumourigenesis, which may be associated with a switch to myometrial infiltration.
authors.affiliation: Unitat de Recerca Biomèdica, Institut de Recerca, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Planagumà
authors.forename: Miguel
authors.initials: M
authors.lastname: Abal
authors.forename: Antonio
authors.initials: A
authors.lastname: Gil-Moreno
authors.forename: María
authors.initials: M
authors.lastname: Díaz-Fuertes
authors.forename: Marta
authors.initials: M
authors.lastname: Monge
authors.forename: Angel
authors.initials: A
authors.lastname: García
authors.forename: Teresa
authors.initials: T
authors.lastname: Baró
authors.forename: Jordi
authors.initials: J
authors.lastname: Xercavins
authors.forename: Jaume
authors.initials: J
authors.lastname: Reventós
authors.forename: Francesc
authors.initials: F
authors.lastname: Alameda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009215:Myometrium / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction / Q000379:methods; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C086680:ETV5 protein, human; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D014157:Transcription Factors