Apoptosis is inhibited early in the dysplasia-carcinoma sequence of Barrett esophagus.
OBJECTIVE
To evaluate the alteration of apoptosis in the esophageal epithelium during the esophagitis-Barrett esophagus-adenocarcinoma sequence.


METHODS
Archival tissue samples of 85 lesions in 58 cases were used. The lesions represented 7 groups: normal esophagus (n = 10), reflux esophagitis (n = 12), Barrett metaplasia (n = 21), Barrett low-grade dysplasia (n = 17), Barrett high-grade dysplasia (n = 5), well- or moderately differentiated adenocarcinoma (n = 10), and poorly differentiated adenocarcinoma (n = 10). Apoptotic cells with fragmented DNA were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL) method. Monoclonal antibodies against bcl-2 protein were applied using the avidin-biotin complex immunoperoxidase method.


RESULTS
The esophagitis group showed many apoptotic cells on the epithelial surface; in the other groups, few apoptotic cells were seen. Weak bcl-2 expression was seen in the basal cells in normal subjects and those with esophagitis. There was overexpression of bcl-2 in 72% of Barrett metaplasia, 100% of Barrett low-grade dysplasia, 25% of Barrett high-grade dysplasia, 40% of well- or moderately differentiated adenocarcinoma, and 20% of poorly differentiated adenocarcinoma.


CONCLUSIONS
Increased apoptosis in reflux esophagitis may be a protective mechanism counteracting increased proliferation. Inhibition of apoptosis by overexpression of bcl-2 protein occurs early in the dysplasia-carcinoma sequence of Barrett esophagus. The resulting prolongation of cell survival may promote neoplastic progression. Despite the absence of apoptosis, bcl-2 was not widely overexpressed in Barrett high-grade dysplasia and adenocarcinoma, suggesting that cells acquire other ways of avoiding apoptosis as malignancy appears.
Katada
N
N
Department of Surgery, Creighton University, Omaha, Neb, USA.
Hinder
R A
RA
Smyrk
T C
TC
Hirabayashi
N
N
Perdikis
G
G
Lund
R J
RJ
Woodward
T
T
Klingler
P J
PJ
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000911:Antibodies, Monoclonal; D017209:Apoptosis; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D004942:Esophagitis, Peptic / Q000378:metabolism / Q000473:pathology*; D004947:Esophagus / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology*; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D012016:Reference Values; D013997:Time Factors
D000911:Antibodies, Monoclonal; D019253:Proto-Oncogene Proteins c-bcl-2