title: Expression of ERβ and its co-regulators p300 and NCoR in human transitional cell bladder cancer.
abstract: OBJECTIVE
  Several data support a possible role of estrogens in bladder carcinogenesis, mediated mainly through estrogen receptor-β (ERβ). We study the expression of ERβ and its co-regulators p300 and nuclear co-repressor (NCoR) in patients with bladder cancer.
  
  
  METHODS
  One hundred and eleven consecutive patients (74 males and 37 females), aged 23-90 years (mean 70 ± 10) diagnosed with transitional cell bladder cancer were included in this study. The control group consisted of 29 patients that underwent transurethral prostatectomy and consented to simultaneous bladder biopsies. Immunohistochemical studies took place on formalin-fixed, paraffin-embedded sections from the TUR (transurethral resection) specimens. We studied the expression of ERβ, p300 and NCoR.χ(2) test was used to evaluate the relationship between the histological grade and ERβ expression, grade and co-regulators expression and grade and gender. Spearman rank correlation coefficient (r) was used in order to estimate the direction and strength of correlations between histological grade and ERβ-p300-NCoR expressions. The Cochran-Armitage test for trend was applied in order to examine possible trends across the ordered levels of histological grade.
  
  
  RESULTS
  ERβ was more frequently expressed in the nucleus of normal bladder epithelium compared to malignant bladder epithelium with statistical significant association (r = -0.25, p = 0.003). The p300 was expressed only in the nucleus of bladder cancer cells and a positive correlation between molecular expression and cancer progression was demonstrated (r = 0.55, p < 0.001). NCoR immunostaining was demonstrated in the nuclei of bladder cells. Nuclear staining was significantly higher in normal tissue than in cancer cells (r = -0.33, p < 0.001), with negative correlation. Furthermore, its expression in grade I tumors was significantly higher than in grade II (r = -0.46, p < 0.001) and grade III tumors (r = -0.51, p < 0.001). Thus, like ERβ, NCoR expression in bladder epithelium decreased during cancer progression and loss of cell differentiation. There was no correlation between the levels of expression of the three proteins in normal bladder epithelium, but there was an inverse correlation between the nuclear expression of ERβ and p300 in carcinomas (r = -3.88, p = 0.042). Statistical significant association was established when correlating ERβ expression with NCoR expression (r = 0.273, p = 0.005), while co-regulators' nuclear expression did not correlate with each other (p > 0.05).
  
  
  CONCLUSIONS
  In bladder carcinogenesis, we demonstrated inhibition in the expression of ERβ and its co-repressor NCoR as well as increased expression of the co-activator p300.
authors.affiliation: Department of Anatomy and Histology, School of Medicine, University of Patras, Patras, Greece.
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kontos
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papatsoris
authors.forename: Athina
authors.initials: A
authors.lastname: Kominea
authors.forename: Maria
authors.initials: M
authors.lastname: Melachrinou
authors.forename: Anna
authors.initials: A
authors.lastname: Tanoglidi
authors.forename: Stefanos
authors.initials: S
authors.lastname: Kachrilas
authors.forename: Markos
authors.initials: M
authors.lastname: Karavitakis
authors.forename: Eleni
authors.initials: E
authors.lastname: Balampani
authors.forename: Georgia
authors.initials: G
authors.lastname: Sotiropoulou-Bonikou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D018450:Disease Progression; D050881:E1A-Associated p300 Protein / Q000096:biosynthesis*; D004848:Epithelium / Q000473:pathology; D047629:Estrogen Receptor beta / Q000096:biosynthesis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D056971:Nuclear Receptor Co-Repressor 1 / Q000096:biosynthesis*; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*
chemical_list: D047629:Estrogen Receptor beta; C539127:NCOR1 protein, human; D056971:Nuclear Receptor Co-Repressor 1; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human