Surveillance of patients with Barrett's esophagus for dysplasia and cancer with balloon cytology

Falk, Gary W.; Chittajallu, R. S.; Goldblum, John R.; Biscotti, Charles V.; Geisinger, Kim R.; Petras, Robert E.; Birgisson, Sigurbjörn; Rice, Thomas W.; Richter, Joel E.

doi:10.1053/gast.1997.v112.pm9178668

Cited by 121 publications

(56 citation statements)

References 2 publications

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“…However, its sensitivity for the detection of low-grade dysplasia is limited, which constitutes one of the reasons why cytology is currently only rarely performed as part of routine surveillance in the United States. 29,30 Ancillary …”

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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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%

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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“…Likewise, given that early studies in selected patient groups suggest that genetic and epigenetic markers recovered in stool have potential to detect cancers in the upper digestive tract (49,(51)(52)(53), one could speculate that assay of methylated EYA4 in stool could be explored as a noninvasive approach to screen for Barrett's esophagus or early-stage cancers. Some have suggested nonendoscopic brushings or balloon swabbing of the esophagus as an approach to Barrett's screening (54), and assay of methylated EYA4 or other tumor-specific molecular markers from recovered cells may have an application with such an approach. Assay of methylated EYA4 in serum could be of potential value in staging and postoperative surveillance of esophageal cancer.…”

Section: Eya4 Methylation In Barrett's Esophagusmentioning

confidence: 99%

Frequent Methylation ofEyes Absent 4Gene in Barrett's Esophagus and Esophageal Adenocarcinoma

Zou

Osborn

Harrington

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Most esophageal adenocarcinomas arise within Barrett's esophagus but the cause of this increasingly prevalent condition remains unknown. Early detection improves survival and discriminant screening markers for Barrett's esophagus and cancer are needed. This study was designed to explore the natural history of eyes absent 4 (EYA4) gene methylation in the neoplastic progression of Barrett's esophagus and to evaluate methylated EYA4 as a candidate marker. Aberrant promoter methylation of EYA4 was studied by methylation-specific PCR using bisulfite-treated DNA from esophageal adenocarcinomas, Barrett's esophagus, and normal epithelia, and then confirmed by sequencing. Eight cancer cell lines were treated with the demethylation agent 5-aza-2V -deoxycytidine, and EYA4 mRNA expression with and without treatment was quantified by real-time reverse-transcription PCR. EYA4 hypermethylation was detected in 83% (33 of 40) of esophageal adenocarcinomas and 77% (27 of 35) of Barrett's tissues, but only in 3% (2 of 58) of normal esophageal and gastric mucosa samples (P < 0.001). The unmethylated cancer cell lines had much higher EYA4 mRNA expression than the methylated cancer cell lines. Demethylation caused by 5-aza-2V -deoxycytidine increased the mRNA expression level by a median of 3.2-fold in methylated cells, but its effect on unmethylated cells was negligible. Results indicate that aberrant promoter methylation of EYA4 is very common during tumorigenesis in Barrett's esophagus, occurs in early metaplasia, seems to be an important mechanism of down-regulating EYA4 expression, and represents an intriguing candidate marker for Barrett's metaplasia and esophageal cancer.

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“…Conventional cytology is not routinely performed on endoscopic brushings obtained from patients with Barrett's esophagus in most institutions, and there are relatively few studies that have addressed the sensitivity and specificity of cytology for the detection of dysplasia and adenocarcinoma in patients with Barrett's esophagus. However, a study by Falk and colleagues 11 demonstrated that balloon cytology had a sensitivity of 80% for the detection of high-grade dysplasia and adenocarcinoma, a sensitivity of 25% for low-grade dysplasia, and a specificity of 95%.…”

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confidence: 99%

The Development of a Fluorescence in Situ Hybridization Assay for the Detection of Dysplasia and Adenocarcinoma in Barrett's Esophagus

Brankley

Wang

Harwood

et al. 2006

The Journal of Molecular Diagnostics

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The goal of this study was to identify a set of fluorescence in situ hybridization probes for the detection of dysplasia and adenocarcinoma in patients with Barrett's esophagus. We examined 170 brushing specimens from 138 patients with Barrett's esophagus or a history of Barrett's esophagus using fluorescence in situ hybridization with probes to 5p15, 5q21-22, centromere 7, 7p12, 8q24.12-13, centromere 9, 9p21, centromere 17, 17p13.1, 17q11.2-12, 20q13.2, and centromere Y. Receiver-operator curves were used to determine the sensitivity and specificity of various four-probe combinations for detecting low-grade dysplasia, high-grade dysplasia, and esophageal adenocarcinoma. Endoscopic biopsy results were used as the gold standard. Numerous four-probe combinations provided a similarly high sensitivity and specificity. Of these, a set consisting of probes to 8q24, 9p21, 17q11.2, and 20q13.2 was found to have a sensitivity and specificity, respectively, of 70% and 89% for low-grade dysplasia, 84% and 93% for high-grade dysplasia, and 94% and 93% for esophageal adenocarcinoma. This probe set was chosen for future prospective clinical evaluations based on its high sensitivity and specificity, its ability to distinguish adenocarcinoma and high-grade or low-grade dysplasia from lesser diagnostic categories, and the favorable signal quality for each of the probes. The majority of esophageal adenocarcinomas is thought to arise in patients with Barrett's esophagus. Barrett's esophagus is a preneoplastic condition caused by metaplasia of the normal squamous mucosa of the distal esophagus into specialized intestinal mucosa containing goblet cells.1 Individuals with Barrett's esophagus have a 30-to 60-fold elevated risk of developing adenocarcinoma and develop adenocarcinoma at a rate of ϳ0.5 to 1.0% per year of follow-up. 2-5The American College of Gastroenterology has recommended that Barrett's esophagus patients be monitored for the development of dysplasia and adenocarcinoma by undergoing regular endoscopic examinations of the esophagus and obtaining four-quadrant biopsies for every 1 to 2 cm of affected esophagus.6,7 However, there are problems associated with the use of biopsies for monitoring Barrett's esophagus patients for the development of neoplasia including: 1) limited sampling of the affected mucosa leading to false-negative biopsy results, 8 2) lengthy procedure time required to take fourquadrant biopsies every 1 to 2 cm, 7 3) poor interobserver reproducibility of pathologists for the diagnosis of dysplasia, 9 and 4) relatively poor ability of histological findings to predict which patients are likely to progress to adenocarcinoma.10 Assays that improve the ability to accurately detect dysplasia and esophageal adenocarcinoma as well as predict which patients will progress to adenocarcinoma could markedly improve the clinical management of these patients. Conventional cytology is not routinely performed on endoscopic brushings obtained from patients with Barrett's esophagus in most institutions, and there are rel...

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Surveillance of patients with Barrett's esophagus for dysplasia and cancer with balloon cytology

Cited by 121 publications

References 2 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

Frequent Methylation ofEyes Absent 4Gene in Barrett's Esophagus and Esophageal Adenocarcinoma

The Development of a Fluorescence in Situ Hybridization Assay for the Detection of Dysplasia and Adenocarcinoma in Barrett's Esophagus

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