Flow-cytometric and histological progression to malignancy in Barrett's esophagus: Prospective endoscopic surveillance of a cohort

Reid, Brian J.; Blount, Patricia L.; Rubin, Cyrus E.; Levine, Douglas S.; Haggitt, Rodger C.; Rabinovitch, Peter S.

doi:10.1016/0016-5085(92)90758-q

Cited by 414 publications

(139 citation statements)

References 21 publications

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“…26,27 Brush cytology may be complementary to endoscopic biopsies, and is recommended by some to be part of the routine endoscopic surveillance of patients with Barrett's esophagus. 28 Cytology has a good sensitivity for the detection of adenocarcinoma and HGD, as well as a good specificity for intestinal metaplasia without dysplasia.…”

Section: Discussionmentioning

confidence: 99%

“…26,27 A variety of gains and losses of specific chromosomes and chromosome regions have also been detected in esophageal adenocarcinoma specimens and adjacent mucosa by both traditional cytogenetics and by comparative genomic hybridization. [34][35][36][37][38][39] The studies consistently show an accumulation of chromosomal abnormalities as the histologic changes progress from intestinal metaplasia to dysplasia and carcinoma.…”

Section: Discussionmentioning

confidence: 99%

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Chromosomal gains and genomic loss of p53 and p16 genes in Barrett's esophagus detected by fluorescence in situ hybridization of cytology specimens

et al. 2004

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Endoscopic brush cytology is a promising surveillance technique for Barrett's esophagus. Ancillary markers are sought to increase the sensitivity of cytology and allow identification of patients at increased risk for disease progression. To determine if there are specific genetic changes in Barrett's esophagus with associated high-grade dysplasia/intramucosal adenocarcinoma compared to those without dysplasia, we performed fluorescence in situ hybridization (FISH) on cytologic specimens using probes to chromosomes and genomic regions previously described as altered in this disease. We studied archival brush cytology slides from 40 Barrett's esophagus patients: 21 with biopsy-proven high-grade dysplasia/carcinoma and 19 with no dysplasia and a minimum 5 years of negative follow-up. Centromeric enumeration probes (CEP) for chromosomes 6, 7, 11, and 12, and locus-specific probes (LSI) for 9p21 (p16 gene), and 17p13.1 (p53 gene) loci along with their corresponding CEP (9 and 17, respectively) were used in this study. A positive FISH result was defined as the presence of cells with 42 CEP signals or with a loss of the LSI signals relative to their corresponding CEP. p53 locus loss and/or aneusomy of chromosomes 6, 7, 11, and 12 abnormalities could be detected by FISH in routinely processed endoscopic brush cytology specimens from 95% of biopsy-positive cases with a specificity of 100%. Interestingly, all five cases with cytologic changes classified as indefinite for dysplasia from patients with a positive biopsy showed changes by FISH. Loss of the p16 locus was seen commonly in patients both with and without dysplasia/carcinoma. Selected biomarkers from this study merit further investigation to determine their potential to detect genetic changes in patients with Barrett's esophagus prior to the development of high-grade dysplasia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Chromosomal gains and genomic loss of p53 and p16 genes in Barrett's esophagus detected by fluorescence in situ hybridization of cytology specimens

et al. 2004

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“…[51][52][53] These high grade dysplastic lesions may already have irreversibly progressed; at least 50% have immediately adjacent adenocarcinoma and a variable proportion of the rest may remain static for at least 1 to 3 years regardless of the presence or absence of refluxed gastric or duodenal contents. 53,54 Dysplastic cells may have proliferative controls that are relaxed or uncoupled from the appropriate regulatory cues. In part this may be a result of altered expression of cytokines and growth factors, 40 although the acquisition of genomic alterations of cell cycle-associated genes also occurs.…”

Section: Dysplasia and Aneuploidy: Clonal Expansion By Increased Cellmentioning

confidence: 99%

Molecular Evolution of the Metaplasia-Dysplasia-Adenocarcinoma Sequence in the Esophagus

Jankowski

Wright

Meltzer

et al. 1999

The American Journal of Pathology

365

254

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The incidence of adenocarcinoma of the esophagus has been increasing in developing countries over the last three decades and probably reflects a genuine increase in the incidence of its recognized precursor lesion , Barrett's metaplasia. Despite advances in multimodality therapy , the prognosis for invasive esophageal adenocarcinoma is poor. An improved understanding of the molecular biology of this disease may allow improved diagnosis , therapy , and prognosis. We focus on recent developments in the molecular and cell biology of Barrett's metaplasia , a heterogeneous lesion affecting the transitional zone of the gastro-esophageal junction whose associated molecular alterations may vary both in nature and temporally. Early premalignant clones produce biological and genetic heterogeneity as seen by multiple p53 mutations , p16 mutations , aneuploidy , and abnormal methylation resulting in stepwise changes in differentiation , proliferation , and apoptosis , allowing disease progression under selective pressure. Abnormalities in expression of growth factors of the epidermal growth factor family and cell adhesion molecules, especially cadherin/catenin complexes , may occur early in invasion. Exploitation of these molecular events may lead to a more appropriate diagnosis and understanding of these lesions in the future. (Am J Pathol 1999, 154:965-973)

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“…On the other hand, the presence of mtDNA mutation only in Barrett's epithelium could be explained with the ®eld cancerization theory (Slaughter et al, 1954), implying that metaplastic Barrett's epithelium of these patients would be at increased risk for cancer development. Multiple areas of various degrees of dysplasia can exist in the same patient with Barrett's esophagus or Barrett's cancer, including the occurrence of multiple aneuploid cell populations (Reid et al, 1992;Neshat et al, 1994), and progression to cancer in patients with Barrett's esophagus has been shown to be associated with increased genomic instability (Rabinovitch et al, 1989). It is therefore likely that a mtDNA mutationnegative clone with a selective growth advantage formed a malignant tumor, and an area of Barrett's epithelium with an acquired mtDNA mutation was at an earlier step in the process of tumorigenesis.…”

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confidence: 99%

Mutations in the mitochondrial DNA D-Loop region occur frequently in adenocarcinoma in Barrett's esophagus

et al. 2002

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Mitochondrial DNA (mtDNA) is known for high mutation rates caused by lack of protective histones, ine cient DNA repair systems, and continuous exposure to mutagenic e ects of oxygen radicals. We examined the frequency of mutations in the mtDNA D-Loop region in 20 patients with Barrett's carcinoma and associated Barrett's epithelium by automated DNA sequencing. Mutations were detected in eight of 20 (40%) patients in tumor and/or tumor-associated Barrett's epithelium. In six of eight positive cases, the mutations were detected only in the tumor, one of eight showed mutations in tumor and Barrett's epithelium, and one of eight only in Barrett's epithelium. The degree of dysplasia in Barrett's epithelium was classi®ed low-grade in one and high grade in the two specimens. There was no association of mtDNA D-Loop mutations with histopathological stage of disease or tumor grading. We present the ®rst study of frequent occurrence of mutations in the mtDNA D-Loop regions in adenocarcinomas in Barrett's esophagus. Furthermore, this study supports the hypothesis that oxidative damage might be a mechanism for the induction of adenocarcinoma in Barrett's esophagus. Since mutations were identi®ed in tumor-associated dysplastic Barrett's epithelium, they also might become a marker for the malignant potential of Barrett's epithelium.

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Flow-cytometric and histological progression to malignancy in Barrett's esophagus: Prospective endoscopic surveillance of a cohort

Cited by 414 publications

References 21 publications

Chromosomal gains and genomic loss of p53 and p16 genes in Barrett's esophagus detected by fluorescence in situ hybridization of cytology specimens

Chromosomal gains and genomic loss of p53 and p16 genes in Barrett's esophagus detected by fluorescence in situ hybridization of cytology specimens

Molecular Evolution of the Metaplasia-Dysplasia-Adenocarcinoma Sequence in the Esophagus

Mutations in the mitochondrial DNA D-Loop region occur frequently in adenocarcinoma in Barrett's esophagus

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