Histopathologic Evaluation of an Animal Model for Barrett’s Esophagus and Adenocarcinoma of the Distal Esophagus

Buskens, Christianne J.; Hulscher, Jan B F; Gulik, Thomas M. van; Kate, Fiebo J. ten; Lanschot, J. Jan B. van

doi:10.1016/j.jss.2006.04.023

Cited by 38 publications

(70 citation statements)

References 21 publications

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“…In summary, although endoscopic resection cannot currently be recommended in cases of Barrett's adenocarcinoma with submucosal infiltration, it is gaining in popularity as a curative technique. [13][14][15][16] Recently, Lin et al 17 demonstrated that the lack or low-intensity staining of AMACR in a cohort of 163 colorectal carcinoma is significantly correlated with poor tumor differentiation (P ¼ 0.021), and presence of lymphovascular invasion (Po0.032). In our study, we did not find a significant correlation between staining score and these criteria.…”

Section: Lymph Vessel Infiltration and Poor Tumor Gradementioning

confidence: 99%

Expression of α-methylacyl coenzyme A racemase in the dysplasia carcinoma sequence associated with Barrett’s esophagus

Scheil-Bertram¹,

Lorenz²,

Ell³

et al. 2008

Modern Pathology

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Two different studies demonstrated a-methylacyl coenzyme A racemase (AMACR) to be a highly specific marker in Barrett's neoplastic lesions. Reactive atypia was positive in 3/30 cases in these studies. We present a retrospective study of early Barrett's adenocarcinoma treated with surgery (2000-2005, n ¼ 29; M:F ¼ 5:1, median age 67 years). We analyzed the role of AMACR expression in reactive and neoplastic lesions associated with the disease of 77 different specimens (60 biopsy and 17 surgical specimens) of these patients. In our cohort, 70% of cases demonstrated infiltration of the submucosa, 38% were poorly differentiated, and/or 31% demonstrated lymph vessel infiltration. We used a multi-tissue array, with reactive and neoplastic samples for each patient to analyze the immunoreactivity of AMACR. Barrett's epithelium that was negative for dysplasia and columnar epithelial cell changes indefinite for dysplasia (n ¼ 30) did not demonstrate AMACR immunoreactivity. AMACR immunoreactivity was demonstrated in 27% (8/30) of cases of Barrett's epithelium with columnar epithelial cell changes indefinite for dysplasia. Altogether 91% of cases with low-grade dysplasia were AMACR-positive and 96% of cases with high-grade dysplasia and early Barrett's adenocarcinoma were positive for AMACR. In summary, the sensitivity of AMACR expression in low-grade dysplasia and subsequent early Barrett's adenocarcinoma was significantly higher in our study compared with previous data. This might be a new diagnostic marker for dysplasia carcinoma sequence in Barrett's low-grade neoplastic lesions. Further studies are required to investigate this point with well-defined controls having at least 5-years follow-up.

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Section: Lymph Vessel Infiltration and Poor Tumor Gradementioning

confidence: 99%

Expression of α-methylacyl coenzyme A racemase in the dysplasia carcinoma sequence associated with Barrett’s esophagus

Scheil-Bertram¹,

Lorenz²,

Ell³

et al. 2008

Modern Pathology

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“…[1][2][3] Epidemiological studies indicate a strong relationship between GERD and esophageal adenocarcinoma, [4][5][6][7] with the risk of malignant transformation being 30-to 125-fold higher in GERD patients complicated with BE. 8,9 The origin and pathological progression of BE and the contribution of gastroesophageal reflux in the disease process have been extensively studied in animal models.…”

mentioning

confidence: 99%

“…8,9 The origin and pathological progression of BE and the contribution of gastroesophageal reflux in the disease process have been extensively studied in animal models. 1,[10][11][12][13] The metaplastic process of BE appears to be a protective adaptation 14 or a regenerative healing mechanism. 15 It is hypothesized that 'pleuripotent cells' from the native esophageal stratified squamous epithelium or ductal epithelium of the esophageal submucosal glands may give rise to the specialized columnar epithelium.…”

mentioning

confidence: 99%

Repeated exposure to acid and bile selectively induces colonic phenotype expression in a heterogeneous Barrett's epithelial cell line

Bajpai

Liu

Geng

et al. 2008

Laboratory Investigation

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Barrett's epithelium is a precancerous, specialized columnar metaplasia in the distal esophagus. We demonstrate the changes in cellular phenotype in a non-neoplastic Barrett's cell line (BAR-T), following exposure to acid and bile salt, the two important components of gastroesophageal refluxate. Cell phenotypes in BAR-T cell line were quantified by fluorescence-activated cell sorting (FACS) using monoclonal antibodies against markers: cytokeratin 8/18 (CK8/18) for columnar, CK4 for squamous, mAbDas-1 for colonic epithelial cell phenotype and p75NTR for esophageal progenitors. Cells were exposed for 5 min each day to 200 mM glycochenodeoxycholic acid at pH 4, pH 6 and pH 7.4 or only to acid (pH 4) for up to 6 weeks. The BAR-T cell line comprised 35 ± 5.2% CK8/18, 32 ± 3.5% mAbDas-1, 9.5 ± 3% CK4 and 4 ± 2.5% p75NTR-positive cells. Single exposure to acid and or bile did not change cell phenotypes. However, chronic treatment for at least 2 weeks significantly enhanced (Po0.05) the expression of colonic phenotype and CK8/18-positive cells, as evidenced by FACS analysis. Bile salt at pH 4 and bile salt followed by acid (pH 4) in succession were the strongest stimulators (Po0.01) for induction of colonic phenotype cells. Squamous (CK4 þ ) phenotype did not change by the treatments. Cox-2 expression was induced after acute treatment and increased to twofold during chronic treatment, particularly in response to acidic pH. We conclude that BAR-T cells can be utilized as an 'in vitro' model to study the effect of environmental factors and their influence on the cellular phenotype and molecular changes in the pathogenesis of esophageal cancer.

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“…The role of bile reflux has been established from surgical models in rats, where esophagojejunostomy and esophagogastroduodenostomy results in a mixed bile and gastric refluxate that leads to intestinal metaplasia, with many similarities to human BE, including early induction of Cdx1 and Cdx2 expression and the development of a columnar-lined epithelium containing intestinal mucin-secreting goblet cells, [21][22][23][24][25] and esophageal adenocarcinoma. 26,27 Bile acids, particularly unconjugated bile acids such as deoxycholate that induce DNA damage, are one component of gastroduodenal reflux that has been strongly linked to the development of BE, as well as to other cancers a leucine-rich orphan G protein-coupled receptor, was shown to specifically label stem cells in the small intestinal and colon crypts, the so-called crypt based columnar (CBC) cells. 61,62 Activation of Wnt signaling in Lgr5+ cells was able to induce intestinal neoplasia.…”

Section: Proton Pump Inhibitor Therapy and Hypergastrinemia In Bementioning

confidence: 99%

Barrett esophagus

et al. 2012

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T he incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the western world and accounts for 2% of all cancer-related deaths. The precursor lesion for EAC is Barrett esophagus (BE), which is strongly associated with gastresophageal reflux disease. A major limitation to the study of EAC has been the absence of tractable and genetically modifiable preclinical models of BE. A mouse model of BE and EAC that resembles human disease could provide novel insights into the origins and molecular pathogenesis of BE. In addition, validated animal models could help stratify BE patients given the limited predictive power of current standard endoscopic measures and clinical assessment. Here, we review the findings from recently developed mouse models of BE and EAC and their impact on clinical decision making, surveillance programs and therapeutic options. The data, taken together, suggest potential origins of BE from the gastric cardia, a role of bile acid and hypergatrinemia for carcinogenesis, a growing importance for columnar-like epithelium and a critical role for Notch signaling.

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Histopathologic Evaluation of an Animal Model for Barrett’s Esophagus and Adenocarcinoma of the Distal Esophagus

Cited by 38 publications

References 21 publications

Expression of α-methylacyl coenzyme A racemase in the dysplasia carcinoma sequence associated with Barrett’s esophagus

Expression of α-methylacyl coenzyme A racemase in the dysplasia carcinoma sequence associated with Barrett’s esophagus

Repeated exposure to acid and bile selectively induces colonic phenotype expression in a heterogeneous Barrett's epithelial cell line

Barrett esophagus

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