PTU-193 Gastro-oesophageal reflux (GORD) and coeliac disease: a bidirectional study

Abstract

quadrantic biopsies. DNA content abnormalities (aneuploidy/tetraploidy); loss of heterozygosity (LOH) at 9p and 17p loci; RUNX3, HPP1 and p16 methylation; immunohistochemistry (IHC) for p53 and Cyclin A were tested on targeted biopsies. Each biomarker was correlated with the dysplasia and AFI status. Results 111 patients with 210 biopsy areas were included in the analysis (AFI+, n¼120; AFI-, n¼90). Univariate per-biopsy analysis showed that all biomarkers correlated with dysplasia (p<0.05), with exception of 9p LOH. Multivariate analysis showed that aneuploidy, p53 IHC and Cyclin A (3 biomarker panel) were independently associated with dysplasia with an AUC¼0.93 (95% CI 0.88 to 0.98) for any dysplasia and AUC¼0.95 (95% CI 0.89 to 1) for HGD/early cancer (EC). AFI positivity significantly correlated with aneuploidy, p16 methylation, cyclin A and p53 staining (p<0.05). After excluding dysplastic areas, aneuploidy (p¼0.03) and p53 (p¼0.04) staining retained statistical correlation with AFI positivity. Analysis of the 3 biomarker panel in patients with dysplasia showed significant biomarker enrichment in AFI+ compared to AFI-areas (p¼0.001). Finally, 3 biomarker panel was used to predict prevalent dysplasia. Using a cut-off of $2 biomarkers, the panel when applied to AFI+ areas alone, showed sensitivity and specificity of 88% and 90% respectively for diagnosis of HGD/EC, and 64% and 96% respectively for diagnosis of any dysplasia, compared to overall histology. Conclusion AFI increases detection rate for molecular biomarkers. A panel of 3 molecular biomarkers on a small number of AFI targeted biopsies can efficiently predict the dysplasia status and potentially inform therapeutic management of patients with BE.