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Superoxide Dismutases in Gastric and Esophageal Cancer and the Prognostic Impact in Gastric Cancer¹

Departments of Gastroenterology and Hepatology [A. M. L. J., C. B. B., W. v. D., M. M. O-v. d. R., F. J. G. M. K., G. G., C. B. H. W. L., H. W. V.], Pathology [J. H. J. M. v. K.], and Oncologic Surgery [C. J. H. v. d. V.], Leiden University Medical Center, 2300 RC Leiden, the Netherlands

The oxidant-antioxidant balance is thought to be important in the initiation, promotion, and therapy resistance of cancer. In the present study, we assessed the expression of the antioxidants manganese superoxide dismutase (Mn-SOD) and copper/zinc superoxide dismutase in gastric and esophageal carcinomas and their relation with clinical outcome. Adenocarcinomas of the stomach (n = 81) as well as squamous cell carcinomas of the esophagus (n = 10) showed an enhanced immunohistochemical expression of Mn-SOD, which was accompanied by a significantly higher tissue level (P 0.007) compared with their corresponding normal mucosa. In contrast, copper/zinc superoxide dismutase was found to be marginally lower in these malignant tissues in comparison with the normal tissues. The superoxide dismutase levels were not found to be associated with major clinicopathological features of the gastric cancer patients. Univariate analysis revealed, however, that a high Mn-SOD level in gastric carcinomas, a low level in the normal gastric mucosa, and a high ratio of these two levels in gastric cancer patients are indicative of a poor overall survival. Multivariate analysis, including all clinicopathological parameters, revealed that the Mn-SOD ratio in particular is an independent prognostic parameter in gastric cancer patients. Although the mechanism(s) that up-regulate Mn-SOD in gastric and esophageal cancer, which is also thought to confer therapy resistance, are not yet fully elucidated, it seems to be clinically relevant for patients’ survival, similar to that as previously reported for colorectal cancer.

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