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Molecular Alterations of Barrett's Esophagus on Microdissected Endoscopic Biopsies
Alterations in proto-oncogenes and tumor suppressor genes play a role in the sequence from Barrett’s metaplasia to esophageal adenocarcinoma. The present study aims to ascertain whether molecular abnormalities take place in Barrett’s metaplasia and low-grade dysplasia and to correlate them with the...
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Published in: | Laboratory investigation 2001-02, Vol.81 (2), p.241-247 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Alterations in proto-oncogenes and tumor suppressor genes play a role in the sequence from Barrett’s metaplasia to esophageal adenocarcinoma. The present study aims to ascertain whether molecular abnormalities take place in Barrett’s metaplasia and low-grade dysplasia and to correlate them with the histological features of the esophageal mucosa. Forty-one formalin-fixed, paraffin-embedded endoscopic esophageal biopsies were classified according to the type of metaplastic changes (noncolumnar fundic and cardial metaplasia; columnar metaplasia, with and without intestinal features). After microdissection samples were examined for loss of heterozygosity (LOH) using polymorphic markers on 5q (D5S82), corresponding to
APC
(
adenomatous polyposis coli
) gene, 13q (CA repeat in intron 2 position 14815 to 14998 of the retinoblastoma gene), 17p (D17S513) corresponding to
p53
locus, and for
p53
mutations. Molecular alterations including LOH, allelic imbalance, and microsatellite instability could be detected in all types of metaplastic changes and sporadically in the squamous epithelium adjacent to the metaplastic tissue. Molecular alterations involving microsatellites D5S82 and the CA repeat inside the retinoblastoma gene were more frequent in nonintestinal metaplasia whereas those involving the
p53
locus took place in columnar intestinal metaplasia and in low-grade dysplasia. Clonal changes were demonstrated in different metaplastic areas in three patients. Genetic alterations comprising LOH and microsatellite instability characterize Barrett’s mucosa and appear related to the type of metaplastic change. Some of them precede the development of intestinal metaplasia, suggesting that genetic alterations take place earlier than previously thought. |
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ISSN: | 0023-6837 1530-0307 |
DOI: | 10.1038/labinvest.3780232 |