Differential expression of the nuclear receptors farnesoid X receptor (FXR) and pregnane X receptor (PXR) for grading dysplasia in patients with Barrett's oesophagus

A van de Winkel, KPM van Zoest, H van Dekken… - …, 2011 - Wiley Online Library
A van de Winkel, KPM van Zoest, H van Dekken, LMG Moons, EJ Kuipers…
Histopathology, 2011Wiley Online Library
van de Winkel A, van Zoest KPM, van Dekken H, Moons LMG, Kuipers EJ & van der Laan
LJW (2011) Histopathology58, 246–253 Differential expression of the nuclear receptors
farnesoid X receptor (FXR) and pregnane X receptor (PXR) for grading dysplasia in patients
with Barrett's oesophagus Aims: 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. Methods and results: Immunostaining was …
van de Winkel A, van Zoest K P M, van Dekken H, Moons L M G, Kuipers E J & van der Laan L J W 
(2011) Histopathology58, 246–253
Differential expression of the nuclear receptors farnesoid X receptor (FXR) and pregnane X receptor (PXR) for grading dysplasia in patients with Barrett’s oesophagus
Aims:  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.
Methods and 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.
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