title: Epithelial turnover in duodenal familial adenomatous polyposis: A possible role for estrogen receptors?
abstract: OBJECTIVE
  To investigate estrogen receptors expression in duodenal familial adenomatous polyposis (FAP) and any relationship with epithelial proliferation/apoptosis markers.
  
  
  METHODS
  Twenty-two patients affected by FAP undergoing duodenal resection for malignancies were recruited. Controls were 15 healthy subjects undergoing endoscopy for dyspeptic symptoms. ER-α, ER-α, Ki-67, TUNEL and caspase 3 expression (labeling index: percentage of positive cells) were evaluated by immunohistochemistry or immunofluorescence and examined by light or confocal microscopy. Samples were assigned to four groups: normal tissue, low (LGD) and high-grade dysplasia (HGD), adenocarcinoma (AC). One-way analysis of variance, corrected by Bonferroni's test, and Pearson's correlation test were applied for statistical analysis.
  
  
  RESULTS
  ER-beta showed a progressive decline: normal tissue (23.5 ± 4.9), LGD (21.1 ± 4.8), HGD (9.3 ± 3.5), AC (7.1 ± 3.1). The normal tissue of FAP subjects expressed ER-beta like the controls (23.9 ± 6.2). Conversely, ER-α showed a progressive increase from normal tissue (24.8 ± 5.6) to AC (52.0 ± 8.2); the expression in normal tissue was similar to controls (22.5 ± 5.3). Ki67 demonstrated a statistically significant progressive increase at each disease stage up to AC. TUNEL did not reveal differences between controls and normal tissue of FAP subjects, but progressive decreases were observed in LGD, through HGD to AC. Pearson's correlation test showed a direct relationship between ER-β and TUNEL LI (r = 0.8088, P < 0.0001). Conversely, ER-α was inversely correlated with TUNEL LI (r = - 0.7257, P < 0.0001). The co-expression of ER-β and caspase 3 declined progressively from normal to neoplastic tissue.
  
  
  CONCLUSIONS
  This study confirmed that ER-β is strongly decreased in duodenal FAP carcinomas, declining in a multiple step fashion, thereby suggesting a putative anti-carcinogenic effect. ER-α showed the opposite trend. ER-β/caspase 3 co-expression suggests this hormone's possible involvement in apoptosis. Hormonal influences in FAP duodenal tumorigenesis, and modulation of these as a possible chemoprevention strategy, may be a promising approach.
authors.affiliation: Alfredo Di Leo, Mariabeatrice Principi, Bruna Girardi, Maria Pricci, Giuseppe Losurdo, Andrea Iannone, Enzo Ierardi, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Leo
authors.affiliation: Alfredo Di Leo, Mariabeatrice Principi, Bruna Girardi, Maria Pricci, Giuseppe Losurdo, Andrea Iannone, Enzo Ierardi, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Nesi
authors.affiliation: Alfredo Di Leo, Mariabeatrice Principi, Bruna Girardi, Maria Pricci, Giuseppe Losurdo, Andrea Iannone, Enzo Ierardi, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Mariabeatrice
authors.initials: M
authors.lastname: Principi
authors.affiliation: Alfredo Di Leo, Mariabeatrice Principi, Bruna Girardi, Maria Pricci, Giuseppe Losurdo, Andrea Iannone, Enzo Ierardi, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Piscitelli
authors.affiliation: Alfredo Di Leo, Mariabeatrice Principi, Bruna Girardi, Maria Pricci, Giuseppe Losurdo, Andrea Iannone, Enzo Ierardi, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Bruna
authors.initials: B
authors.lastname: Girardi
authors.affiliation: Alfredo Di Leo, Mariabeatrice Principi, Bruna Girardi, Maria Pricci, Giuseppe Losurdo, Andrea Iannone, Enzo Ierardi, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Pricci
authors.affiliation: Alfredo Di Leo, Mariabeatrice Principi, Bruna Girardi, Maria Pricci, Giuseppe Losurdo, Andrea Iannone, Enzo Ierardi, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Losurdo
authors.affiliation: Alfredo Di Leo, Mariabeatrice Principi, Bruna Girardi, Maria Pricci, Giuseppe Losurdo, Andrea Iannone, Enzo Ierardi, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Iannone
authors.affiliation: Alfredo Di Leo, Mariabeatrice Principi, Bruna Girardi, Maria Pricci, Giuseppe Losurdo, Andrea Iannone, Enzo Ierardi, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Ierardi
authors.affiliation: Alfredo Di Leo, Mariabeatrice Principi, Bruna Girardi, Maria Pricci, Giuseppe Losurdo, Andrea Iannone, Enzo Ierardi, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tonelli
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D011125:Adenomatous Polyposis Coli / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D000328:Adult; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D053148:Caspase 3 / Q000032:analysis; D049109:Cell Proliferation; D004379:Duodenal Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D004386:Duodenum / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D047628:Estrogen Receptor alpha / Q000032:analysis*; D047629:Estrogen Receptor beta / Q000032:analysis*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry / Q000473:pathology* / Q000601:surgery; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C506487:ESR1 protein, human; C000600034:ESR2 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D019394:Ki-67 Antigen; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Confocal microscopy; Duodenal cancer; Dysplasia; Estrogen receptors; Familial adenomatous polyposis; Immunohistochemistry