MARKERS OF DISEASE PROGRESSION IN BARRETT'S ESOPHAGUS

Fred Hutchinson Cancer Research Center, Seattle WA

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Abstract

Esophageal adenocarcinoma (EA) has had a rise in incidence of more than 350 percent in the last 20 years and has a 5-year survival rate of less than 10 percent. The precursor lesion for this disease, Barrett's esophagus, is a metaplastic tissue that arises as a complication of gastroesophageal reflux, which affects more than 25 million people in the US. Identification of markers predictive of who is at risk for developing EA is critical for improving survival of this disease. Loss of heterozygosity on chromosome 18 has been found frequently in EA and occurs before the development of cancer, suggesting possible utility as a marker of disease progression. Chromosome 18 LOH will be examined in 50 consecutive patients with EA, using 16 microsatellite markers along the length of the chromosome. Analyses will be facilitated by using flow purified cell populations and fluorescence-based PCR detection of LOH. The data obtained from this study will be combined with that from previous studies of other somatic genetic alterations that occur in EA to give a comprehensive view of the molecular changes that occur during disease progression. Samples from patients who have undergone spontaneous or treatment-induced regression of Barrett's metaplasia will be examined to determine if this apparently normal epithelium contains the same genetic alterations as the original premalignant tissue. These studies will provide information about the progenitor cells that give rise to Barrett's metaplasia and will impact how treatment of BE is evaluated.