title: Correlation between the DNA global methylation status and progesterone receptor expression in normal endometrium, endometrioid adenocarcinoma and precursors.
abstract: Endometrial carcinomas are the most common malignancy of the female genital tract and the third most common cancer in women. Progesterone and oestrogen receptors (PRs, ERs) are the most widely documented prognostic and predictive factors in endometrioid adenocarcinoma. Besides the hormonal pathway involved in the progression of preneoplastic and neoplastic lesions, alterations of the DNA methylation status have been shown to be an early signal of tumorigenesis. In this study, we show that in normal endometrium, during the proliferative phase, DNA methylation and PR expression are high, with a significant decline towards the end of the secretory phase and a gradual increase in non-atypical and atypical endometrial hyperplasia; they reach their highest level in grade I, then decrease significantly in grade-II and grade-III endometrioid adenocarcinomas. During each stage, a significant positive correlation is observed between DNA methylation and PR (P<0.0001). The strong parallelism between DNA methylation and PR expression precludes establishing a precise determination regarding the timing of these events, clearly involved in the genesis of endometrioid adenocarcinoma.
authors.affiliation: Anatomie Pathologique, Bat 10, Hôpital Edouard Herriot, 69003 Lyon, France.
authors.forename: Lina
authors.initials: L
authors.lastname: Ghabreau
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Roux
authors.forename: Alain
authors.initials: A
authors.lastname: Niveleau
authors.forename: Bernard
authors.initials: B
authors.lastname: Fontanière
authors.forename: Cédric
authors.initials: C
authors.lastname: Mahe
authors.forename: Moncef
authors.initials: M
authors.lastname: Mokni
authors.forename: Lucien
authors.initials: L
authors.lastname: Frappart
mesh_terms: D018269:Carcinoma, Endometrioid / Q000378:metabolism*; D019175:DNA Methylation; D004714:Endometrial Hyperplasia / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011230:Precancerous Conditions / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000096:biosynthesis*
chemical_list: D011980:Receptors, Progesterone