p16(INK4a) lesions are common, early abnormalities that undergo clonal expansion in Barrett's metaplastic epithelium

Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma, a cancer of which the incidence has been increasing at an alarming rate in Western countries. p16(INK4a) lesions occur frequently in esophageal adenocarcinomas but their role in neoplastic progression is not well...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2001-11, Vol.61 (22), p.8284-8289
Main Authors: Wong, D J, Paulson, T G, Prevo, L J, Galipeau, P C, Longton, G, Blount, P L, Reid, B J
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Aneuploidy
Barrett Esophagus - genetics
Barrett Esophagus - pathology
Biopsy
Chromosomes, Human, Pair 9
Clone Cells
CpG Islands
Cyclin-Dependent Kinase Inhibitor p16 - genetics
DNA Methylation
Epithelial Cells - pathology
Esophageal Neoplasms - genetics
Esophageal Neoplasms - pathology
Humans
Loss of Heterozygosity
Metaphase - genetics
Middle Aged
Mutation
Precancerous Conditions - genetics
Precancerous Conditions - pathology
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Summary:Barrett's esophagus (BE) is the only known precursor to esophageal adenocarcinoma, a cancer of which the incidence has been increasing at an alarming rate in Western countries. p16(INK4a) lesions occur frequently in esophageal adenocarcinomas but their role in neoplastic progression is not well understood. We detected 9p21 loss of heterozygosity, p16 CpG island methylation, and p16 mutations in biopsies from 57%, 61%, and 15%, respectively, of 107 patients with BE. In contrast, no mutations were found in p14(ARF) or p15, and methylation was found in only 4% and 13%, respectively. >85% of Barrett's segments had clones with one (p16+/-) or two (p16-/-) p16 lesions. Both p16+/- and p16-/- clones underwent extensive expansion involving up to 17 cm of esophageal mucosa. The prevalence of established biomarkers in BE, such as 17p (p53) loss of heterozygosity, aneuploidy, and/or increased 4N (tetraploid) populations, increased from 0% to 20% to 44% in patients whose biopsies were p16+/+, p16+/-, and p16-/-, respectively (P < 0.001). Barrett's segment lengths also increased with change in p16 status with a median of 1.5, 6.0, and 8.0 cm for patients with p16+/+, p16+/-, and p16-/- biopsies, respectively (P < 0.001). We conclude that most Barrett's metaplasia contains genetic and/or epigenetic p16 lesions and has the ability to undergo clonal expansion, creating a field in which other abnormalities can arise that can lead to esophageal adenocarcinoma.
ISSN:0008-5472