TY - JOUR
T1 - Apoptosis is inhibited early in the dysplasia-carcinoma sequence of Barrett esophagus
AU - Katada, Natsuya
AU - Hinder, Ronald A.
AU - Smyrk, Thomas C.
AU - Hirabayashi, Naoki
AU - Perdikis, Galen
AU - Lund, Richard J.
AU - Woodward, Timothy
AU - Klingler, Paul J.
PY - 1997
Y1 - 1997
N2 - Objective: To evaluate the alteration of apoptosis in the esophageal epithelium during the esophagitis-Barrett esophagus-adenocarcinoma sequence. Design: 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 deoxy- nucleotidyl 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.
AB - Objective: To evaluate the alteration of apoptosis in the esophageal epithelium during the esophagitis-Barrett esophagus-adenocarcinoma sequence. Design: 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 deoxy- nucleotidyl 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.
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U2 - 10.1001/archsurg.1997.01430310042007
DO - 10.1001/archsurg.1997.01430310042007
M3 - Article
C2 - 9230856
AN - SCOPUS:0030829281
SN - 2168-6254
VL - 132
SP - 728
EP - 733
JO - JAMA Surgery
JF - JAMA Surgery
IS - 7
ER -