title: Stromal Clues in Endometrial Carcinoma: Loss of Expression of β-Catenin, Epithelial-Mesenchymal Transition Regulators, and Estrogen-Progesterone Receptor.
abstract: Epithelial-stroma interactions in the endometrium are known to be responsible for physiological functions and emergence of several pathologic lesions. Periglandular stromal cells act on endometrial cells in a paracrine manner through sex hormones. In this study, we immunohistochemically evaluated the expression of epithelial-mesenchymal transition regulators (SNAIL/SLUG, TWIST, ZEB1), adhesion molecules (β-catenin and E-cadhenin), estrogen (ER)-progesterone (PR) receptor and their correlation with each other in 30 benign, 148 hyperplastic (EH), and 101 endometrioid-type endometrial carcinoma (EC) endometria. In the epithelial component, loss of expression in E-cadherin, ER and PR, and overexpression of TWIST and ZEB1 were significantly higher in EC than in EH (P<0.01). In the periglandular stromal component, β-catenin and SNAIL/SLUG expression were significantly higher in normal endometrium and simple without atypical EH compared with complex atypical EH and EC (P<0.01). In addition, periglandular stromal TWIST expression was significantly higher in EH group compared with EC (P<0.05). There was significantly negative correlation between β-catenin and ER, TWIST and ER, and TWIST and PR in hyperplastic and carcinomatous glandular epithelium, whereas there was a significantly positive correlation between β-catenin and SNAIL-SLUG, β-catenin and TWIST, β-catenin and ER, β-catenin and PR, SNAIL-SLUG and ER, SNAIL-SLUG and PR, TWIST and ER, TWIST and PR, in periglandular/cancer-associated stromal cells (P<0.01). In conclusion, the pattern of positive and negative correlations in the expression of epithelial-mesenchymal transition regulators (SNAIL-SLUG and TWIST), sex hormone receptors (ER and PR), and β-catenin between ECs and hyperplasia, as well as between epithelium and stroma herein, is suggestive of a significant role for these proteins and their underlying molecular processes in the development of endometrial carcinomas.
authors.affiliation: Department of Pathology (S.S., A.B.C., P.E.Z., A.A.), Faculty of Medicine, Istanbul Medeniyet University, Goztepe Research and Training HospitalDepartment of Medical Genetics (I.A.), Faculty of Medicine, Istanbul Medeniyet UniversityDepartment of Pathology (D.K.), Van Research and Training District Hospital, VanDepartment of Pathology (I.S.), Faculty of Medicine, Erzincan University, ErzincanDepartment of Pathology (I.I., U.F.), Faculty of Medicine, Dicle University, Diyarbakir, Turkey.
authors.forename: Serkan
authors.initials: S
authors.lastname: Senol
authors.forename: Ilyas
authors.initials: I
authors.lastname: Sayar
authors.forename: Ayse B
authors.initials: AB
authors.lastname: Ceyran
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Ibiloglu
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Akalin
authors.forename: Ugur
authors.initials: U
authors.lastname: Firat
authors.forename: Duygu
authors.initials: D
authors.lastname: Kosemetin
authors.forename: Pinar
authors.initials: P
authors.lastname: Engin Zerk
authors.forename: Abdullah
authors.initials: A
authors.lastname: Aydin
mesh_terms: D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000378:metabolism / Q000473:pathology*; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D051176:beta Catenin