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Association of Manganese Superoxide Dismutase Expression With Progression of Carcinogenesis in Barrett Esophagus
Bruce Hermann, MD;
Yan Li, PhD;
Mukunda B. Ray, MD;
John M. Wo, MD;
Robert C. G. Martin II, MD
Arch Surg. 2005;140:1204-1209.
Hypothesis The down-regulation of manganese superoxide dismutase (MnSOD) expression plays a role in the progression of Barrett esophagus (BE).
Design An evaluation of 92 esophageal samples, including 17 patients with normal esophagus, 22 with intestinal metaplasia, 22 with indefinite/low-grade dysplasia, 16 with high-grade dysplasia (HGD), and 15 with esophageal adenocarcinoma were evaluated for MnSOD expression. We evaluated MnSOD expression using immunohistochemistry and graded it separately on a 2-category ordinal scale in relation to the mucosa and submucosa that ranged from 0 (no staining) to 3 (strong staining). The total grading score of MnSOD immunoreactivity was the addition of mucosa and submucosa intensity, from 0 (no immunoreactivity in any of the anatomic sites) to a maximum score of 6 (strong staining reaction in both of the histoanatomic sites).
Setting Study subjects were recruited from the Barrett’s Esophageal Registry at the University of Louisville, Louisville, Ky.
Main Outcome Measure Manganese superoxide dismutase expression in established groups of progressive BE.
Results Ninety-two samples were evaluated for MnSOD expression. The expression of MnSOD was found to be significantly reduced in samples with specialized intestinal metaplasia (mean score, 1.8), low-grade dysplasia (mean, 2.2), high-grade dysplasia (mean, 2.4), and esophageal adenocarcinoma (mean, 2.4) when compared with normal esophagus (mean, 3.9; P = .002). Manganese superoxide dismutase expression was similar for esophageal adenocarcinoma and high-grade dysplasia.
Conclusions Manganese superoxide dismutase expression is significantly reduced in patients with BE with high-grade dysplasia and esophageal adenocarcinoma. Manganese superoxide dismutase is related to the progression of BE and may represent one of the primary factors in oxidative stress protection. Further evaluation within genotypic expression and the role of antioxidants is needed in the effective screening and treatment of BE.
Author Affiliations: Department of Surgery, Division of Surgical Oncology (Drs Hermann, Li, and Martin), Department of Pathology (Dr Ray), and Department of Medicine, Division of Gastroenterology/Hepatology (Dr Wo), University of Louisville School of Medicine, Louisville, Ky.
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