Novel biomarkers for risk stratification of Barrett’s oesophagus associated neoplastic progression–epithelial HMGB1 expression and stromal lymphocytic phenotype
Menée à partir de l'analyse immuno-histochimique de 436 échantillons de tissus œsophagiens normaux ou présentant un endobrachyœsophage ou un adénocarcinome, cette étude met en évidence une association entre l'expression de la protéine HMGB1 au niveau des cellules épithéliales, la progression néoplasique de l'œsophage et le phénotype des lymphocytes ayant infiltré le stroma
Background : 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.
Methods : Subcellular 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).
Results : There 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.
Conclusions : This 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.
British Journal of Cancer , résumé, 2019