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PTU-172 C-Myc as a Biomarker in Barrett’S Oesophagus
  1. S Varghese1,
  2. C S Ross-Innes1,
  3. P Lao-Sirieix1,
  4. M O’Donovan2,
  5. R C Fitzgerald1
  1. 1Hutchison/MRC Research Centre
  2. 2Dept. of Pathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

Abstract

Introduction Identifying Barrett’s oesophagus (BE) patients at risk of progressing to oesophageal adenocarcinoma (EA) remains a challenge. Diagnosis of low grade dysplasia is limited by considerable intra and inter-observer variability and inflammation in biopsy samples can lead to a diagnosis of indefinite for dysplasia. Immunostaining using molecular biomarkers would therefore be useful as a diagnostic adjunct in the assessment of dysplasia.

The Aim of this study was to identify and validate a molecular biomarker that can objectively determine dysplasia status and thereby determine cancer risk in BE.

Methods Biomarkers of interest were identified through mining of a microarray gene expression dataset from 59 oesophageal samples with strict consensus diagnosis by expert pathologists [21 BE with no dysplasia (NDBE), 10 BE with low grade dysplasia (LGD), 13 BE with high grade dysplasia (HGD) and 8 EA]. Subsequent validation was performed on a BE tissue microarray (TMA) (60 NDBE, 19 LGD and 29 HGD), and EA TMA (n = 278).

Results Seventy eight genes were differentially expressed between NDBE and HGD. c-MYC was selected as a top target as the expression levels progressively increased with dysplasia stage and cancer with a fold change of 2.46 between NDBE and HGD. mRNA expression levels were significantly higher in HGD and EA compared to NDBE (p < 0.0001). Immunostaining for c-MYC was positive in 25 out of 29 cases of HGD with a sensitivity 86% of and a specificity of 97% (Table 1). 10 out of 19 LGD stained positive for MYC. 254 out of 278 (91%) EA cases showed significant c-MYC protein expression. Among the 19 LGD samples, 9 had HGD in the BE segment and 7 of these were positive for c-MYC. Strong c-MYC staining was also observed in areas regarded as indefinite for dysplasia which were adjacent to areas of HGD.

Abstract PTU-172 Table 1

Table 1. Immunohistochemistry for c-MYC in oesophageal samples. NDBE: Non-dysplastic Barrett’s oesophagus, LGD: Low-grade dysplasia, HGD: High grade dysplasia.

Conclusion Immunohistochemistry for c-MYC is a promising molecular biomarker in Barrett’s oesophagus. It could also enable better risk stratification in patients with samples in the LGD and indefinite for dysplasia categories.

Disclosure of Interest None Declared.

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