Characterization of the mechanisms that promote progression of Barrett’s esophagus may lead to the identification of genetic markers that predict risk of malignancy.
In this study, researchers used fluorescence in situ hybridization (FISH) to determine when specific genetic alterations arise during Barrett’s associated neoplastic progression.
|Metaplastic tissues displayed increased copy numbers of chromosomes 4 and 8.|
Their findings are published in the May issue of Gut.
The research team obtained endoscopic cytology brushings from 28 patients with Barrett’s metaplasia, 28 with dysplasia, and 7 with adenocarcinoma. They also obtained paired control brushings from regions of normal proximal squamous cell epithelium.
The exfoliated epithelial cells were washed and deposited onto slides.
Probes specific for the centromeres of chromosomes 4, 8, 20, and Y, and locus specific probes for the tumor suppressor genes p16, p53, and Rb were subsequently hybridized.
The team found aneuploidy early in progression. Metaplastic tissues displayed increased copy numbers of chromosomes 4 and 8.
Chromosome 4 hyperploidy was found in 89%, 90%, 88%, and 100% of the metaplasia, low grade dysplasia, high grade dysplasia and adenocarcinoma samples, respectively. In addition, chromosome 8 hyperploidy occurred in 71%, 75%, 100%, and 100% of patients with the respective staging.
Loss of the p16 tumor suppressor gene also presented in metaplastic epithelium.
Most other genetic aberrations were only seen in high grade dysplasia.
Dr Doak's team concluded, "Genetic instability arises well before dysplasia in Barrett’s esophagus, with chromosome 4 and 8 hyperploidy representing the earliest and most common alterations identified".
"As these aberrations are widespread at all the premalignant stages, there may be genes on chromosomes 4 and 8 that are involved in both the initiation and progression of Barrett’s esophagus".