title: Differential expression of the nuclear receptors farnesoid X receptor (FXR) and pregnane X receptor (PXR) for grading dysplasia in patients with Barrett's oesophagus.
abstract: OBJECTIVE
  To investigate expression of nuclear receptors farnesoid X receptor (FXR) and pregnane X receptor (PXR) as a diagnostic tool to improve grading of dysplasia in Barrett's oesophagus patients.
  
  
  RESULTS
  Immunostaining was analysed on a total of 192 biopsy samples of 22 Barrett's patients with no dysplasia (ND), 17 with low-grade dysplasia (LGD), 20 high-grade dysplasia (HGD) and 24 with adenocarcinoma (AC). Nuclear FXR expression was observed in 15 of 22 (68%) ND cases versus none of 19 HGD; 3 of 17 (18%); LGD; 5 of 60 (8%) patients with AC (P<0.001). FXR expression was highly specific for non-dysplastic tissue. Nuclear PXR was expressed in 16 of 20 (80%) HGD cases versus two of 16 (13%) LGD cases (PPV 89%). Upon examining adjacent tissue taken from HGD and AC patients, PXR expression was high in samples of all tissue types.
  
  
  CONCLUSIONS
  Nuclear receptors are expressed differentially during neoplastic progression, with FXR positivity being useful to distinguish ND from dysplasia and AC. PXR nuclear expression is able to separate HGD from LGD and ND. The combination of FXR and PXR also appears to have diagnostic and possibly prognostic value, but future prospective studies are required to investigate their predictive power for neoplastic progression in Barret's oesophagus.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, The Netherlands. a.vandewinkel@erasmusmc.nl
authors.forename: Anouk
authors.initials: A
authors.lastname: van de Winkel
authors.forename: Katinka P M
authors.initials: KP
authors.lastname: van Zoest
authors.forename: Herman
authors.initials: H
authors.lastname: van Dekken
authors.forename: Leon M G
authors.initials: LM
authors.lastname: Moons
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Luc J W
authors.initials: LJ
authors.lastname: van der Laan
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology*; D000077297:Pregnane X Receptor; D012372:ROC Curve; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis*; D011987:Receptors, Steroid / Q000096:biosynthesis*; D012680:Sensitivity and Specificity; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D014408:Biomarkers, Tumor; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D000099150:Receptor, Farnesoid X-Activated