Evolving management of metaplasia and dysplasia in Barrett's epithelium

Evans, Richard; Mourad, Moustafa Mabrouk; Fisher, S; Bramhall, Simon R.

doi:10.3748/wjg.v22.i47.10316

Cited by 5 publications

(4 citation statements)

References 76 publications

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“…( B ) The three main epithelial interfaces that occur in BE to EAC progression. Pictures were adapted from figure 2 of (49). ( C ) Overview of the experimental procedure, described in steps 1-3.…”

Section: Resultsmentioning

confidence: 99%

Motion Sensing Superpixels (MOSES): A systematic framework to quantify and discover cellular motion phenotypes

Zhou

Ruiz‐Puig

Owen

et al. 2018

Preprint

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17Cellular motion is fundamental in tissue development and homeostasis. There is strong 18interest in identifying factors that affect the interactions of cells in disease but analytical tools 19for robust and sensitive quantification in varying experimental conditions for large extended 20 timelapse acquisitions is limited. We present Motion Sensing Superpixels (MOSES), a 21 method to systematically capture diverse features of cellular dynamics. We quantify dynamic 22interactions between epithelial cell sheets using cell lines of the squamous and columnar 23 epithelia in human normal esophagus, Barrett's esophagus and esophageal 24 adenocarcinoma and find unique boundary formation between squamous and columnar cells. 25MOSES also measured subtle changes in the boundary formation caused by external stimuli. 26The same conclusions of the 190 videos were arrived at unbiasedly with little prior 27 knowledge using a visual motion map generated from unique MOSES motion 'signatures'. 28MOSES is a versatile framework to measure, characterise and phenotype cellular 29interactions for high-content screens. 30 31 32 Keywords : optical flow, collective motion, dynamic meshes, motion phenotypes 33 34 35 36 37 38 39 40 41 42 130 be used in-vivo and to label primary cells (30). We tested the effects of the dye in two 131 populations of EPC2, filmed over 96 and 144 hrs (Supp. Movie 1). The green and red 132 fluorescent labelled EPC2 cells proliferated similarly, exhibiting the same cell density over 133 the time course (slope=0.976, Pearson correlation coefficient 0.978; automatically counted 134from DAPI staining) (Fig.1D, Supp.Fig.1) and migrated similarly (assessed by the mean 135 squared displacement (31)) (Supp. Fig 2). Thus, the dye has a minimal impact on cell motion 136

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Section: Resultsmentioning

confidence: 99%

Motion Sensing Superpixels (MOSES): A systematic framework to quantify and discover cellular motion phenotypes

Zhou

Ruiz‐Puig

Owen

et al. 2018

Preprint

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“… 2 Barrett’s oesophagus (BO) is a pre-malignant 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.…”

Section: Introductionmentioning

confidence: 99%

“…Currently, the pathogenesis of metaplastic-dysplastic-malignant progression is not fully understood. 3 , 9 However, there have been a variety of proposed biomarkers to aid this risk stratification 10 , including transcriptional changes, 11 tissue microRNAs 12 , 13 or circulating glycoproteins 14 and breath volatiles. 15 …”

Section: Introductionmentioning

confidence: 99%

Novel biomarkers for risk stratification of Barrett’s oesophagus associated neoplastic progression–epithelial HMGB1 expression and stromal lymphocytic phenotype

et al. 2019

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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.

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“…Currently, diagnosis of BE require endoscopic identification of columnar mucosa extending above the GEJ, plus the presence of intestinal metaplasia (IM) with goblet cells [5,7,8]. The management of BE can vary greatly depending on the presence and severity of dysplasia [9]. Although the overall risk of progression of BE to ECA/GEJ Aca is low (2.7% in patients without dysplasia and around 6% in patients with low grade dysplasia (LGD)), the risk increases to 25% in patients with high-grade dysplasia (HGD).…”

Section: Introductionmentioning

confidence: 99%

Maspin differential expression patterns as a potential marker for targeted screening of esophageal adenocarcinoma/gastroesophageal junction adenocarcinoma

et al. 2019

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Aim Barrett’s esophagus (BE) is a predisposing factor of esophageal adenocarcinoma/gastroesophageal junction adenocarcinoma (ECA/GEJ Aca). BE patients are stratified and subsequently monitored according to the risk of malignant progression by the combination of endoscopy and biopsy. This study is to evaluate the maspin expression patterns as early diagnostic markers of malignancy in BE patients. Materials and methods Immunohistochemistry (IHC) staining was performed on 62 archival core biopsies from 35 patients, including BE without dysplasia (intestinal metaplasia, IM), BE with low grade dysplasia, BE with high grade dysplasia, carcinoma in situ , and well to poorly differentiated ECA/GEJ Aca (PD-ECA/GEJ Aca). The intensity and the subcellular distribution of immunoreactivity were evaluated microscopically. Statistical analysis was performed using the χ 2 and Fisher exact tests. Results The level of epithelial-specific tumor suppressor maspin protein inversely correlated with the progression from IM to PD-ECA/GEJ Aca. Lesions of each pathological grade could be divided into subtypes that exhibited distinct maspin subcellular distribution patterns, including nuclear only (Nuc), combined nuclear and cytoplasmic (Nuc+Cyt), cytoplasmic only (Cyt) and overall negligible (Neg). The Cyt subtype, which was minor in both IM and dysplasia (approximately 10%), was predominant in ECA/GEJ Aca as early as well-differentiated lesions (more than 50%: p = 0.0092). In comparison, nuclear staining of the tumor suppressor TP53 was heterogeneous in dysplasia, and did not correlate with the differentiation grades of ECA/GEJ Aca. Conclusion The Cyt subtype of maspin expression pattern in core biopsies of BE patients may serve as a molecular marker for early diagnosis of ECA/GEJ Aca.

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Evolving management of metaplasia and dysplasia in Barrett's epithelium

Cited by 5 publications

References 76 publications

Motion Sensing Superpixels (MOSES): A systematic framework to quantify and discover cellular motion phenotypes

Motion Sensing Superpixels (MOSES): A systematic framework to quantify and discover cellular motion phenotypes

Novel biomarkers for risk stratification of Barrett’s oesophagus associated neoplastic progression–epithelial HMGB1 expression and stromal lymphocytic phenotype

Maspin differential expression patterns as a potential marker for targeted screening of esophageal adenocarcinoma/gastroesophageal junction adenocarcinoma

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