Up-regulation of ERM/ETV5 correlates with the degree of myometrial infiltration in endometrioid endometrial carcinoma

Jesús Planagumà, Miguel Abal, Antonio Gil-Moreno, María Díaz-Fuertes, Marta Monge, Ángel García, Teresa Baró, Jordi Xercavins, Jaume Reventós, Francesc Alameda

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33 Citations (Scopus)

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. Copyright © 2005 Pathological Society of Great Britain and Ireland.
Original languageEnglish
Pages (from-to)422-429
JournalJournal of Pathology
Volume207
Issue number4
DOIs
Publication statusPublished - 1 Dec 2005

Keywords

  • Differential gene expression
  • Endometrial endometrioid carcinoma
  • Endometrial tissue microarray
  • ERM/ETV5

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