Glutathione S-transferases (GST) are enzymes involved in the detoxification of xenobiotics and are divided into four subclasses, Alpha, Mu, Pi, and Theta. Most human gastrointestinal tumors contain increased amounts of GST Pi and GST enzyme activity. The relationship between GST parameters and tumor and patient characteristics, including overall survival, were studied retrospectively in normal and malignant gastric tissue from 49 patients with primary gastric carcinoma. Twelve patients (24%) were alive at the end of the study with a mean follow-up time of 4.1+/-0.4 years. Levels of GST Alpha, Mu, Pi and GST enzyme activity were not related to tumor stage, localization and diameter of the tumor, number of eosinophils in the tumor, presence of intestinal metaplasia in normal gastric mucosa, or gender and age of the patient. Optimal dichotomization and uni- and multivariate analyses were done with the Cox proportional hazard model. None of the clinicopathological parameters were associated with survival, except the number of eosinophils in the tumor. In contrast, high levels of GST Pi in both normal mucosa (Hazard ratio 3.0, p=0.02) and in gastric carcinoma (HR 2.2, p=0.05) and the presence of GST Mu in normal (HR 0.4, p=0.05) and malignant (HR 0.3, p=0.009) gastric tissue were found to have a significant prognostic value, independent from the clinicopathological parameters, when added separately to a Cox model. In conclusion, the levels of GST Mu and Pi in both normal or carcinomatous gastric tissue have an independent prognostic impact on overall survival.

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