Neosquamous epithelium does not typically arise from Barrett's epithelium.
OBJECTIVE
Neosquamous epithelium (NSE) can arise within Barrett's esophagus as a consequence of medical or surgical acid reduction therapy, as well as after endoscopic ablation. Morphologic studies have suggested that NSE can develop from adjacent squamous epithelium, submucosal gland ducts, or multipotent progenitor cell(s) that can give rise to either squamous or Barrett's epithelium, depending on the luminal environment. The cells responsible for Barrett's epithelium self-renewal are frequently mutated during neoplastic progression. If NSE arises from the same cells that self-renew the Barrett's epithelium, the two tissues should be clonally related and share genetic alterations; if NSE does not originate in the self-renewing Barrett's, NSE and Barrett's esophagus should be genetically independent.


METHODS
We isolated islands of NSE and the surrounding Barrett's epithelium from 20 patients by microdissection and evaluated each tissue for genetic alterations in exon 2 of CDKN2A or exons 5 to 9 of the TP53 gene. Nine patients had p16 mutations and 11 had TP53 mutations within the Barrett's epithelium.


RESULTS
In 1 of 20 patients, a focus of NSE had a 146 bp deletion in p16 identical to that found in surrounding Barrett's epithelium. The NSE in the remaining 19 patients was wild-type for p16 or TP53.


CONCLUSIONS
Our mutational data support the hypothesis that, in most circumstances, NSE originates in cells different from those responsible for self-renewal of Barrett's epithelium. However, in one case, NSE and Barrett's epithelium seem to have arisen from a progenitor cell that was capable of differentiating into either intestinal metaplasia or NSE.
Paulson
Thomas G
TG
Division of Human Biology and Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA. tpaulson@fhcrc.org
Xu
Lianjun
L
Sanchez
Carissa
C
Blount
Patricia L
PL
Ayub
Kamran
K
Odze
Robert D
RD
Reid
Brian J
BJ
D000368:Aged; D001471:Barrett Esophagus / Q000235:genetics / Q000473:pathology*; D001483:Base Sequence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004848:Epithelium / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D042282:Microdissection; D009154:Mutation / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53