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J Thorac Cardiovasc Surg 2004;126:1952-1957
© 2004 The American Association for Thoracic Surgery

General thoracic surgery

Simultaneous progression of oxidative stress and angiogenesis in malignant transformation of Barrett esophagus

^a Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland
^b Department of Biosciences, Helsinki University, Helsinki, Finland

Read at the Eighty-third Annual Meeting of The American Association for Thoracic Surgery, Boston, Mass, May 4-7, 2003.

Received for publication April 25, 2003; revisions received August 11, 2003; accepted for publication August 19, 2003.

^* Address for reprints: Jarmo A. Salo, MD, PhD, Department of Cardiothoracic Surgery, Section of General Thoracic and Esophageal Surgery, Helsinki University Central Hospital, PO Box 340, Haartmaninkatu 4, FIN-00290 Helsinki, Finland
jarmo.salo{at}hus.fi

BACKGROUND: Oxidative stress and angiogenesis are important elements in the pathogenesis of inflammatory diseases and cancer. Our aim was to evaluate the role of both and of antioxidant capacity in the metaplasia-dysplasia-adenocarcinoma sequence in Barrett epithelium.

METHODS: In mucosal specimens from 59 patients grouped as having symptomatic gastroesophageal reflux disease, Barrett epithelium, or adenocarcinoma in the esophagus, plus controls, we measured myeloperoxidase activity, superoxidase dismutase activity, glutathione content, and total aromatic DNA adducts. To evaluate blood vessel densities and angioarchitecture, we used immunohistochemistry and a modified whole-mount technique. Sections were stained with endothelium-specific markers and smooth muscle cell actin.

RESULTS: The reflux disease–metaplasia-carcinoma sequence revealed progressively increased oxidative stress (increased myeloperoxidase activity), decreased antioxidant capacity (glutathione content), and simultaneous formation of DNA adducts. Pooled data show a negative correlation between glutathione content and DNA adducts (-0.28; P = .05). This sequence was also characterized by increased intensity in microvessels and an increasing percentage of immature blood vessels. In addition, the whole-mount technique offered 3-dimensional evidence that the rich new vascular bed is highly abnormal, with repeated twists, bends, or turns, even in nonmalignant Barrett esophagus.

CONCLUSIONS: Increased oxidative stress, decreased antioxidant capacity, and a negative correlation between glutathione content and DNA adduct formation indicate a link between oxidative stress and malignant transformation of Barrett epithelium. Simultaneously, this transformation acquires angiogenic capacity, strong neovascularization, and abnormal angioarchitecture.