title: Altered expression of ERs, aromatase, and COX2 connected to estrogen action in type 1 endometrial cancer biology.
abstract: In order to study estrogen-driven microenvironment associated with type 1 endometrial carcinoma, we evaluated estrogen receptors (ERs), aromatase, and cyclooxygenase II (COX2) molecular and immunohistochemical profiles with correlation to clinicopathological features. We investigated aromatase, ERα, ERβ, and COX2 expression at the mRNA and protein levels using quantitative real-time PCR and immunohistochemical method in 51 endometrial carcinomas and 16 normal endometria. All the studied tumors, as well as normal endometria, expressed ERα, ERβ, and COX2 mRNAs. Five endometrial carcinoma tissues and one normal endometrium showed no aromatase mRNA expression. The majority of tumors expressed ERα (82%), aromatase (80%), and COX2 (88%) proteins. Forty-one percent of the studied tumors were ERβ-negative. ERα and ERβ showed significantly decreased mRNA and protein expression levels in endometrial carcinoma as compared to normal endometrium. An opposite trend was shown for COX2 and aromatase proteins. ERα expression correlated positively with COX2 expression at both mRNA and protein levels (P < 0.005, r = 0.398; P < 0.0005, r = 0.510, respectively). There was also a positive correlation between COX2 and aromatase expression in cancer tissue (P < 0.002, r = 0.433 for transcriptional level; P < 0.0005, r = 0.614 for protein level). We observed positive correlations between ERβ and ERα, as well as between ERβ and COX2 at the transcriptional level only (P < 0.0005, r = 0.644; P < 0.002, r = 0.444, respectively). Negative correlations were found between pT category of primary tumor and levels of ERα and ERβ transcripts (P < 0.02, r = -0.332; P < 0.02, r = -0.348, respectively). A negative association between ERβ and the International Federation of Gynecology and Obstetrics (FIGO) staging was also found. The growth of EC1 with the presence of ERα and overexpression of aromatase and COX2 is dependent on estrogens. We believe that ERβ may be considered as a potential marker in the progression of disease in endometrial cancer patients.
authors.affiliation: Department of Biology and Pathology of Human Reproduction in Bialystok, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Sklodowskiej 24A, 15-276, Bialystok, Poland, kasia.jarzabek@gmail.com.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jarzabek
authors.forename: Mariusz
authors.initials: M
authors.lastname: Koda
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Walentowicz-Sadlecka
authors.forename: Marek
authors.initials: M
authors.lastname: Grabiec
authors.forename: Piotr
authors.initials: P
authors.lastname: Laudanski
authors.forename: Slawomir
authors.initials: S
authors.lastname: Wolczynski
mesh_terms: D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000378:metabolism / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D008875:Middle Aged; D009367:Neoplasm Staging; D011960:Receptors, Estrogen / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen; D001141:Aromatase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human