title: The sharp decline of beta estrogen receptors expression in long-lasting ulcerative-associated carcinoma.
abstract: OBJECTIVE
  Colorectal carcinoma is an important cause of death in inflammatory bowel diseases, thus requiring surveillance for dysplasia in long-standing ulcerative colitis (UC). Females show a lower incidence probably related to hormonal factors; therefore, a role of estrogen receptors (ERs) has been supposed in carcinoma-associated colitis (CAC) development. Our aim was to identify ER beta/alpha expression in long-lasting pancolitis through each grade of dysplasia to carcinoma and, furthermore, to investigate the simultaneous epithelial apoptosis/proliferation.
  
  
  METHODS
  Forty-eight patients affected by long-lasting pancolitis were retrospectively investigated. Samples were divided into four groups: UC, low-grade dysplasia/high-grade dysplasia (UC-HGD), and CAC. Normal colon samples were used as controls. ER-beta, ER-alpha, Ki-67, and TUNEL expression (labeling/H index) were evaluated by immunohistochemistry.
  
  
  RESULTS
  ER-beta expression revealed an impressive reduction in CAC (10.4 ± 5.1; p < 0.001) compared to controls and UC (34.3 ± 3.1 and 26.8 ± 7.8, respectively), meanwhile ER-beta level in LGD (29.4 ± 3.7) was comparable to UC. As far ER-beta/ER-alpha mean value ratio revealed a progressive reduction. Ki67 demonstrated a progressive significant increase from UC until CAC (37.9 ± 6.4 < 45.7 ± 6.2 < 60.6 ± 5.2 < 71.1 ± 5.1; p < 0.001). Apoptotic index (TUNEL) revealed a strong fall in UC-HGD and CAC.
  
  
  CONCLUSIONS
  ER-beta fall could be considered as a biomarker of UC-dysplasia progression. It occurs in HGD and overt neoplasia, while in LGD shows a normal expression. At the moment, we are unable to use this tool in the clinical practice to predict tumor progression, but it would be appropriate to encourage ER expression investigations in large samples for the interesting perspectives of application.
authors: Department of Emergency and Organ Transplantation, Gastroenterology Section, University of Bari , Bari , Italy.
authors: Mariabeatrice
authors: M
authors: Principi
authors: Maria Principia
authors: MP
authors: Scavo
authors: Domenico
authors: D
authors: Piscitelli
authors: Vincenzo
authors: V
authors: Villanacci
authors: Rosa
authors: R
authors: Lovero
authors: Giuseppe
authors: G
authors: Losurdo
authors: Bruna
authors: B
authors: Girardi
authors: Enzo
authors: E
authors: Ierardi
authors: Alfredo
authors: A
authors: Di Leo
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000378:metabolism; D003106:Colon / Q000473:pathology*; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D018450:Disease Progression; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D019394:Ki-67 Antigen
keywords: colorectal carcinoma; dysplasia; estrogen receptors; pancolitis; ulcerative colitis