Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis

Reid, Brian J.; Li, Xiaohong; Galipeau, Patricia C.; Vaughan, Thomas L.

doi:10.1038/nrc2773

Cited by 346 publications

(371 citation statements)

References 212 publications

(242 reference statements)

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“…6,7 When EAC recurs, the anatomic location of recurrence tends to be distant more often than in ESCC. 8,9 Whereas EAC incidence has dramatically increased since 1975 in the United States, ESCC incidence has dropped by half over the same time period.…”

confidence: 99%

The Prognostic Value of Clinical and Pathologic Factors in Esophageal Adenocarcinoma: A Mayo Cohort of 796 Patients With Extended Follow-up After Surgical Resection

Yoon

Khan

Cassivi

et al. 2010

Mayo Clinic Proceedings

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OBJECTIVE: To identify and describe clinicopathologic prognostic factors in patients with esophageal adenocarcinoma who underwent surgical resection with curative intent. PATIENTS AND METHODS:The study cohort consisted of 796 patients with adenocarcinoma of the esophagus, gastroesophageal junction, or gastric cardia who underwent complete tumor resection at Mayo Clinic from January 1, 1980, to December 31, 1997. We reviewed individual patient medical records and abstracted demographic, pathologic, perioperative, and cancer outcome data. Median follow-up for vital status and disease recurrence was 12.8 and 5.8 years, respectively. RESULTS:Univariate analysis revealed the following factors to be statistically associated with worse 5-year disease-specific survival: higher N and T status, higher tumor grade, age older than 76 years, and the presence of extracapsular lymph node extension and signet ring cells. The following factors remained significantly linked with worse 5-year disease-specific survival on multivariate analysis: higher N and T status, grade, and age and the absence of preoperative chemotherapy or radiotherapy. Anatomic location of tumor was not associated with differential prognosis. Lymph node metastases were found in 25 (27%) of 93 T1b tumors, 397 (85%) of 468 T3 tumors, and 22 (67%) of 33 T4a tumors. Diseasespecific survival was better in T3-4N0 than in T1bN1-3 carcinomas (hazard ratio, 0.50; 95% confidence interval, 0.28-0.89, adjusted for grade and age; P=.02). CONCLUSION:Our results confirm the importance of T and N status and tumor grade and suggest that age may affect prognosis. In addition, we show that a significant proportion of superficial esophageal adenocarcinomas exhibit regional metastases and have worse prognosis than more invasive nonmetastatic tumors. Proc. 2010;85(12):1080-1089 AIC = Akaike information criterion; AJCC = American Joint Committee on Cancer; CI = confidence interval; DFS = disease-free survival; DSS = disease-specific survival; EAC = esophageal adenocarcinoma; ESCC = esophageal squamous cell carcinoma; GEJ = gastroesophageal junction; HR = hazard ratio; LN = lymph node; OS = overall survival Mayo Clin © 2010 Mayo Foundation for Medical Education and ResearchT he increase in the incidence of adenocarcinoma of the esophagus, gastroesophageal junction (GEJ), and gastric cardia in recent decades has been among the highest for any cancer in Western countries. 1 This triad of adenocarcinomas (designated esophageal adenocarcinoma [EAC] in this article) has grown more than 400% in incidence in the past 40 years, paralleling the increase in obesity and gastroesophageal reflux. 2 It is lethal in most cases, yet its degree of aggressiveness also varies from person to person. 3 These statistics signal a need for a better understanding of not only EAC etiology, but its progression and long-term clinical behavior. Understanding and exploiting the heterogeneity in prognosis are critical to improving outcomes in EAC patients and require the study of large cohorts with well-descri...

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confidence: 99%

The Prognostic Value of Clinical and Pathologic Factors in Esophageal Adenocarcinoma: A Mayo Cohort of 796 Patients With Extended Follow-up After Surgical Resection

Yoon

Khan

Cassivi

et al. 2010

Mayo Clinic Proceedings

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“…Helicobacter pylori-induced chronic gastritis is a major cause of gastric intestinal metaplasia, from which intestinal-type adenocarcinoma arises (3). Likewise, replacement of the esophageal squamous epithelium by intestinal epithelium known as Barrett's esophagus substantially increases the risk of esophageal adenocarcinoma (2).…”

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confidence: 99%

“…From these observations, we concluded that aberrantly expressed CDX1 endowed gastric epithelial cells with an intestinal stem/progenitor-like phenotype. (1,2). Transgenic expression of Cdx1 has been reported to induce all of those epithelial cell lineages in the mouse stomach (9).…”

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confidence: 99%

“…Metaplastic changes can occur either in a physiological process or a pathological condition, the latter of which predisposes cells to undergo neoplastic transformation via a metaplasia-dysplasia-carcinoma sequence. Intestinal metaplasia, a pathological change of nonintestinal epithelium into an intestinal-like mucosa, is most frequently found in the stomach and esophagus (1,2). Helicobacter pylori-induced chronic gastritis is a major cause of gastric intestinal metaplasia, from which intestinal-type adenocarcinoma arises (3).…”

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confidence: 99%

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CDX1 confers intestinal phenotype on gastric epithelial cells via induction of stemness-associated reprogramming factors SALL4 and KLF5

Fujii

Yoshihashi

Suzuki

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

122

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Intestinal metaplasia of the stomach, a mucosal change characterized by the conversion of gastric epithelium into an intestinal phenotype, is a precancerous lesion from which intestinal-type gastric adenocarcinoma arises. Chronic infection with Helicobacter pylori is a major cause of gastric intestinal metaplasia, and aberrant induction by H. pylori of the intestine-specific caudal-related homeobox (CDX) transcription factors, CDX1 and CDX2, plays a key role in this metaplastic change. As such, a critical issue arises as to how these factors govern the cell-and tissue-type switching. In this study, we explored genes directly activated by CDX1 in gastric epithelial cells and identified stemness-associated reprogramming factors SALL4 and KLF5. Indeed, SALL4 and KLF5 were aberrantly expressed in the CDX1 + intestinal metaplasia of the stomach in both humans and mice. In cultured gastric epithelial cells, sustained expression of CDX1 gave rise to the induction of early intestinal-stemness markers, followed by the expression of intestinal-differentiation markers. Furthermore, the induction of these markers was suppressed by inhibiting either SALL4 or KLF5 expression, indicating that CDX1-induced SALL4 and KLF5 converted gastric epithelial cells into tissue stem-like progenitor cells, which then transdifferentiated into intestinal epithelial cells. Our study places the stemness-related reprogramming factors as critical components of CDX1-directed transcriptional circuitries that promote intestinal metaplasia. Requirement of a transit through dedifferentiated stem/progenitor-like cells, which share properties in common with cancer stem cells, may underlie predisposition of intestinal metaplasia to neoplastic transformation.CagA | Wnt | β-catenin

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“…EAC is becoming increasingly common and its incidence is associated with the prevalent precursor metaplastic condition Barrett's esophagus (BE), but with a low annual conversion rate of up to 1% (27). A common set of risk factors are described for BE and EAC, include gastroesophageal reflux disease (GERD), obesity, male gender, and smoking (28,29). The current endoscopybiopsy based diagnosis is invasive and costly, leading to an ineffective surveillance program.…”

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confidence: 99%

Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma

Shah

Cao

Choi

et al. 2015

Molecular & Cellular Proteomics

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We report an integrated pipeline for efficient serum glycoprotein biomarker candidate discovery and qualification that may be used to facilitate cancer diagnosis and management. The discovery phase used semi-automated lectin magnetic bead array (LeMBA)-coupled tandem mass spectrometry with a dedicated data-housing and analysis pipeline; GlycoSelector (http://glycoselector.di. uq.edu.au). The qualification phase used lectin magnetic bead array-multiple reaction monitoring-mass spectrometry incorporating an interactive web-interface, Shiny mixOmics (http://mixomics-projects.di.uq.edu.au/Shiny), for univariate and multivariate statistical analysis. Relative quantitation was performed by referencing to a spiked-in glycoprotein, chicken ovalbumin. We applied this workflow to identify diagnostic biomarkers for esophageal adenocarcinoma (EAC), a life threatening malignancy with poor prognosis in the advanced setting. EAC develops from metaplastic condition Barrett's esophagus (BE). Currently diagnosis and monitoring of at-risk patients is through endoscopy and biopsy, which is expensive and requires hospital admission. Hence there is a clinical need for a noninvasive diagnostic biomarker of EAC. In total 89 patient samples from healthy controls, and patients with BE or EAC were screened in discovery and qualification stages. Of the 246 glycoforms measured in the qualification stage, 40 glycoforms (as measured by lectin affinity) qualified as candidate serum markers. The top candidate for distinguishing healthy from BE patients' group was Narcissus pseudonarcissus lectin (

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Barrett's oesophagus and oesophageal adenocarcinoma: time for a new synthesis

Cited by 346 publications

References 212 publications

The Prognostic Value of Clinical and Pathologic Factors in Esophageal Adenocarcinoma: A Mayo Cohort of 796 Patients With Extended Follow-up After Surgical Resection

The Prognostic Value of Clinical and Pathologic Factors in Esophageal Adenocarcinoma: A Mayo Cohort of 796 Patients With Extended Follow-up After Surgical Resection

CDX1 confers intestinal phenotype on gastric epithelial cells via induction of stemness-associated reprogramming factors SALL4 and KLF5

Serum Glycoprotein Biomarker Discovery and Qualification Pipeline Reveals Novel Diagnostic Biomarker Candidates for Esophageal Adenocarcinoma

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