Abstract
BackgroundThe incidence of oesophageal adenocarcinoma is increasing globally. Barrett’s oesophagus (BO) is a pre-malignant condition with no biomarker to risk stratify those at highest risk of dysplasia and malignant transformation.MethodsSubcellular epithelial protein (HMGB1, p53, RUNX3) expression, alongside expression of CD20, CD4, CD8 and Foxp3 to characterise stromal B lymphocyte, and helper, cytotoxic and regulatory T-lymphocyte cell infiltrate, respectively, was assessed by immunohistochemistry in 218 human tissue samples including normal oesophageal/gastric biopsies (n = 39), BO (non-dysplasia, dysplasia, non-dysplastic background from progressors to dysplasia or cancer, n = 121) and oesophageal adenocarcinoma (n = 58).ResultsThere is a dynamic subcellular epithelial expression of HMGB1 (loss of nuclear, emergence of cytoplasmic), associated with epithelial p53 expression and differential immune cell phenotype in oesophageal neoplastic progression. We identify a protein signature and lymphocyte infiltrate in non-dysplastic BO when progressive disease (dysplasia or adenocarcinoma) is present but not histologically represented in the biopsied field. There is a dynamic stromal lymphocytic infiltrate in oesophageal neoplastic progression.ConclusionsThis data reveals novel insights into the microenvironment of BO and progression towards cancer and identifies a novel high-risk biomarker of disease progression to aid surveillance strategies to identify early progression and impact future incidence of oesophageal cancer.
Highlights
The incidence of oesophageal adenocarcinoma is increasing globally
Dynamic subcellular expression of high mobility group box-1 (HMGB1) is associated with oesophageal neoplastic progression As expected from its known biology, HMGB1 was strongly expressed in the nuclei of normal oesophageal epithelium
Cytoplasmic expression increased in intensity in both non-dysplastic and dysplastic Barrett’s oesophagus (BO) and remained present in oesophageal adenocarcinoma, weaker in intensity to non-dysplastic BO (p = 0.001) and dysplastic BO (p = 0.002)
Summary
The incidence of oesophageal adenocarcinoma is increasing globally. Barrett’s oesophagus (BO) is a pre-malignant condition with no biomarker to risk stratify those at highest risk of dysplasia and malignant transformation. In the UK,[1] there are 9,000 new cases per year with a 15% 5-year survival.[2] Barrett’s oesophagus (BO) is a premalignant condition for oesophageal adenocarcinoma that affects 1.6–8% of the UK population.[3] BO is defined by histological evidence of epithelial metaplasia from normal stratified squamous epithelium to mucin-secreting columnar epithelium in the distal oesophagus. These metaplastic cells can undergo further transformation to dysplasia or malignancy. The annual incidence of oesophageal adenocarcinoma is 0.33% and 1.40% in non-dysplastic and dysplastic BO, respectfully.[5,6] Cancer incidence has been estimated to be 40-times greater in high grade dysplasia, compared with the general population.[7]
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