Prognostic Significance of the Expressions of Metallothionein, Glutathione-S-Transferase-π, and P-Glycoprotein in Curatively Resected Gastric Cancer

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Abstract
Although experimental studies indicate that overexpression of metallothionein (MT), glutathione-S-transferase-π; (GST-π;), or P-glycoprotein (P-GP) is related to the drug resistance of cancer cells, the clinical significance of the overexpression remains to be elucidated. The expressions of MT, GST-ti, and P-GP were evaluated immunohistochemically in 74 specimens of gastric adenocarcinoma in T1-3N1-2 stages which were resected with curative intent. Fluorinated pyrimidines, mitomycin C, and Adriamycin were prescribed in 73, 54, and 2 patients, respectively. The staining characteristics were investigated in relation to the clinical results. The cell-proliferative activity was studied with anti-proliferating cell nuclear antigen antibody. Expressions of GST-rc and P-GP correlated with the staining intensity of normal mucosa. Five-year disease-free survival rates (DFSRs) of GST-π-negative and GST-π-positive groups were 75.0 and 49.0%. The 5-year DFSRs of P-GP-negative and P-GP-positive groups were 68.2 and 38.6%. Concurrent expression among the three proteins was associated with the survival: 5-year DFSR of no- or one-protein-positive group was 75.0%, while those of 2- and 3-protein-positive groups were 56.0 and 38.9%, respectively. Tumors concurrently expressing 2 or 3 proteins have a high proliferative activity. Expressions of MT, GST-π, and P-GP by the tumor are associated with a poorer prognosis of the patients.

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