Differential expression of the nuclear receptors FXR and PXR for grading dysplasia in patients with Barrett's oesophagus

Aims: To investigate expression of nuclear receptors FXR and PXR as a diagnostic tool to improve grading of dysplasia in Barrett's oesophagus patients. Methods and Results: Immunostaining was analyzed on a total of 192 biopsy samples of of 22 Barrett's patients with no dysplasia (ND), 17 with low grade dysplasia (LGD), 20 high grade dysplasia (HGD), and 24 with adenocarcinoma. Nuclear FXR expression was observed in 15/22 (68%) ND cases versus 5/60 (8%) patients with dysplasia or adenocarcinoma (p<0.001). FXR expression was highly specific for non-dysplastic tissue. Nuclear PXR was expressed in 16/20 (80%) HGD cases versus 2/16 (13%) LGD cases (PPV 89%). Upon examining adjacent tissue taken from HGD and adenocarcinoma patients, PXR expression was high in samples of all tissue types. Conclusions: Nuclear receptors are differentially expressed during neoplastic progression with FXR-positivity being useful to distinguish ND from dysplasia and adenocarcinoma. PXR nuclear expression is able to separate HGD from LGD and ND. The combination of FXR and PXR appears to have diagnosticand possibly prognostic value as well, but future prospective studies are required to investigate their predictive power for dysplastic progression in Barret's oesophagus.