Investigation for Biomarkers of Barrett's Esophagus
Jawad Ahmad*1,2, Ken Arthur3, Perry Maxwell2, Helen G. Mulholland1, J. a. Kennedy2, Liam Murray2, Brian T. Johnston2, Damian T. Mcmanus2
1School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast, United Kingdom; 2Belfast Health and Social Care Trust, Belfast, United Kingdom; 3Tissue CTU, Belfast, United Kingdom
Introduction: The incidence of oesophageal adenocarcinoma (OAC) has increased dramatically over recent years and Barrett’s esophagus (BE) is the most established risk factor for its development. Endoscopic surveillance of BE has been widely advocated but hinges on assessment of repeated endoscopic biopsies, which is problematic and not reliably accurate. The use of biomarkers presents an opportunity to reduce sampling bias and improve our ability to risk-stratify these patients. Aims and Objectives:We examined three novel biomarkers namely P504S, CD133 and Twist, in the setting of BE, low grade dysplasia (LGD) and OAC to evaluate their potential to differentiate between benign, dysplastic and malignant Barrett’s tissue in the EDRN exploratory Phase I & II study.Materials and Methods: After ethical approval, 25 cases each of BE, LGD and OAC were included along-with 25 cases of oesophagectomy resections for Barrett’s OAC. The biomarkers were immunostained on automated Ventana® immunostainer. The archived biopsy materials were assessed for biomarkers expression by two independent observers using a QScore method. Any inter-observer score discrepancy of ≥ 2 was discussed for a consensus.Results: P504S did not express in any case of BE. However, its expression was significant in LGD, OAC and resections. CD133 also did not express in any of the BE or LGD. Its comparative expression was up-regulated in cases of OAC and resections. Twist expression was weak in BE and LGD but over-expressed in cases of OAC and resections. Table 1Discussion: This cross sectional study has shown increased expression of P504S, CD133 and Twist in the metaplasia-dysplasia-adenocarcinoma sequence and has suggested their possible role as potential biomarkers of Barrett’s progression. Further longitudinal and prospective (EDRN III & IV) studies are required to validate these results.
Results
| BE | BE | LGD | LGD | OAC | OAC | Resections | Resections | |
| Biomarker | Positive | Negative | Positive | Negative | Positive | Negative | Positive | Negative |
| P504S | 0 | 25 | 14 (56%) p <0.001 | 11 | 10 (40%) p <0.001 | 15 | 15 (60%) p <0.001 | 10 |
| CD133 | 0 | 25 | 0 | 25 | 6 (24%) p 0.022 | 19 | 17 (68%) p <0.001 | 8 |
| Twist | 1 | 24 | 3 (12%) p 0.609 | 22 | 14 (56%) p <0.001 | 11 | 9 (36%) p 0.005 | 16 |
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