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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


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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