CORRELATION OF GLUTATHIONE S-TRANSFERASES WITH OVERALL SURVIVAL IN PATIENTS WITH GASTRIC-CARCINOMA

Glutathione S-transferases (GST) are enzymes involved in the detoxific ation of xenobiotics and are divided into four subclasses, Alpha, Mu, Pi, and Theta. Most human gastrointestinal tumors contain increased am ounts of GST Pi and GST enzyme activity. The relationship between GST parameters and tumor and patient characteristics, including overall su rvival, were studied retrospectively in normal and malignant gastric t issue from 49 patients with primary gastric carcinoma. Twelve patients (24%) were alive at the end of the study with a mean follow-up time o f 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 tum or, number of eosinophils in the tumor, presence of intestinal metapla sia in normal gastric mucosa, or gender and age of the patient. Optima l dichotomization and uni- and multivariate analyses were done with th e Cox proportional hazard model. None of the clinicopathological param eters 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 (H R 0.3, p=0.009) gastric tissue were found to have a significant progno stic value, independent from the clinicopathological parameters, when added separately to a Cox model. In conclusion, the levels of GST Mu a nd Pi in both normal or carcinomatous gastric tissue have an independe nt prognostic impact on overall survival.