title: Immunohistochemical analysis of steroid receptors, proliferation markers, apoptosis related molecules, and gelatinases in non-neoplastic and neoplastic endometrium.
abstract: Endometrioid endometrial carcinoma developed from endometrial hyperplasia is associated with anomalies of proliferation, apoptosis, and matrix metalloproteinase (MMP) expression. Our study was designed to investigate steroid receptor (ER, PR) expression and its correlation with proliferative activity (PCNA), apoptosis (Fas, FasL, Bcl-2, Bax, and p53), gelatinases (MMP-2 and MMP-9) and their tissue specific inhibitor (TIMP-1 and TIMP-2) immunoexpression in endometrial carcinogenesis. A total of 38 cases were investigated, 10 non-neoplastic, 11 hyperplastic, and 17 carcinomatous endometria. Immunolabeling showed a higher expression of steroid receptors in hyperplasia and carcinoma than in non-neoplastic endometria and an ER/PR imbalance in carcinoma. The epithelial component of endometrial carcinomas had the highest proliferative index. Bcl-2 had a stronger expression in hyperplasia and carcinoma compared to non-neoplastic endometria and stromal tissue. The Bcl-2/Bax ratio was lower in endometrial carcinoma. Fas and FasL expression was stronger in hyperplasia and furthermore in carcinoma. p53 expression was progressively stronger along the sequence non-neoplastic endometrial to hyperplasia-carcinoma. Both types of investigated MMPs showed an increased expression in neoplastic endometria reaching a maximum level in carcinomas. MMP-9 immunostaining could be correlated to myometrial invasion. TIMP-1 decreased and TIMP-2 increased in expression from non-neoplastic endometria to hyperplastic and carcinomatous endometrial, respectively. Our study demonstrates that coordinated anomalies of steroid receptors, apoptosis and invasiveness factors are already present in hyperplasia as cumulative steps along the way to malignant transformation and that a complex MMP-2, MMP-9, TIMP-2/TIMP-1 imbalance seems to be responsible for the endometrial proliferation.
authors.affiliation: University of Medicine and Pharmacy "Gr. T. Popa" Iasi, 16 Universitatii Street, Iasi 700115, Romania.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Amalinei
authors.forename: Corina
authors.initials: C
authors.lastname: Cianga
authors.forename: Raluca
authors.initials: R
authors.lastname: Balan
authors.forename: Petru
authors.initials: P
authors.lastname: Cianga
authors.forename: Simona
authors.initials: S
authors.lastname: Giusca
authors.forename: Irina-Draga
authors.initials: ID
authors.lastname: Caruntu
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D011960:Receptors, Estrogen; D018093:Gelatinases