title: Nuclear type II estradiol binding sites and type I estrogen receptors in human endometrial cancer: a 5-year follow-up study.
abstract: Type II nuclear-estrogen binding sites (type II EBS) have been postulated to play a crucial regulatory role in estrogen-stimulated uterine growth. The pathogenesis of endometrial cancer is known to be connected to estrogens. However, there are no data on type II EBS in human endometrial cancer. Therefore, we investigated the presence of nuclear type II EBS and nuclear type I estrogen receptors (ER) by radioligand-binding assays in endometrial tumorous tissues (n = 135). Determination of cytoplasmic ER and progesterone receptor (PR) concentrations were also included in the study. Estradiol (E2) and progesterone (P) hormone levels in sera of patients were determined by RIAs. In addition, all data were analyzed on 5-year survival rates. Saturation analyses of 3H-E2 binding in crude nuclear pellets (n = 5) showed two types of estradiol binding: type I ER having high affinity and low capacity and type II EBS binding estradiol with lower affinity and high capacity in a positive cooperative fashion. The nuclear type II EBS and type I ER concentrations were significantly higher in cancers of increasing grade. In contrast, a significant decrease of cytoplasmic 3H-E2 binding was detected. Cytoplasmic PR binding capacities were high in G1 and G2, but low in G3 tumors. The 5-year survival data showed nuclear type I ER to have the best correlation for prognostic value (cut-off, 0.5 pmol/mg DNA), while type II EBS had no significant impact on it. Serum E2 concentrations decreased with tumors of higher grade, but were generally still higher than the control values. The serum P levels did not alter. None of the parameters investigated here differed from control values in adenoacanthoma (n = 6), suggesting a separate pathomechanism. As type II EBS are known to be stimulated by E2 under conditions that cause uterine hyperplasia, we concluded that the higher "runaway" nuclear type II EBS levels, in contrast with the lower serum estradiol concentrations, might be connected with the strong proliferative and invasive character of higher grade endometrial adenocarcinomas. This is the first demonstration of the presence of nuclear type II EBS and their possible pathological role in human endometrial cancer, and of the high prognostic significance of nuclear type I ER to identify a subgroup having a fatal form of the disease in a 5-year survival study.
authors.affiliation: Institute of Physiology, University Medical School, Pécs, Hungary.
authors.forename: J L
authors.initials: JL
authors.lastname: Környei
authors.forename: T
authors.initials: T
authors.lastname: Csermely
authors.forename: G
authors.initials: G
authors.lastname: Keller
authors.forename: M
authors.initials: M
authors.lastname: Vértes
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004958:Estradiol / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D011374:Progesterone / Q000097:blood; D011959:Receptors, Estradiol / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D011374:Progesterone; D004958:Estradiol