Loss of heterozygosity on chromosome 17p predicts neoplastic progression in Barrett's esophagus.
OBJECTIVE
Endoscopic surveillance for adenocarcinoma in patients with Barrett's esophagus is costly, with one cancer detected every 48-441 patient years of follow up. Genetic abnormalities, including loss of heterozygosity at sites of tumor suppressor genes, have been detected in malignant and premalignant Barrett's esophagus. The aim of this prospective study was to determine if loss of heterozygosity analysis could identify patients with Barrett's esophagus at greatest risk of adenocarcinoma, for whom endoscopic surveillance is most appropriate.


METHODS
Loss of heterozygosity analysis was performed on endoscopic biopsies from 48 patients as part of a Barrett's surveillance program using 14 microsatellite markers shown previously to detect loss of heterozygosity in more than 30% of esophageal adenocarcinomas. Patients were followed up endoscopically for a median of 5 years.


RESULTS
Loss of heterozygosity was detected in nine patients. Three patients with loss of heterozygosity on chromosome 5q or 9p did not progress beyond metaplasia. Loss of heterozygosity at 17p11.1-p13 was detected in six patients, all of whom demonstrated dysplasia and/or carcinoma during follow up (four low-grade dysplasia, one high-grade dysplasia and one adenocarcinoma).


CONCLUSIONS
Loss of heterozygosity at 17p11.1-p13 on chromosome 17p identifies patients with Barrett's esophagus at risk of neoplastic progression and can supplement histology in determining the frequency of endoscopy during surveillance.
Dolan
Kevin
K
University of Liverpool and Department of Surgery, Royal Liverpool University Hospital, Liverpool, UK. medkd@leeds.ac.uk
Morris
Anthony I
AI
Gosney
John R
JR
Field
John K
JK
Sutton
Robert
R
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D018450:Disease Progression; D016099:Endoscopy, Gastrointestinal; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008679:Metaplasia / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D011237:Predictive Value of Tests; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013223:Statistics as Topic; D016019:Survival Analysis