PROGNOSTIC-SIGNIFICANCE OF THE EXPRESSIONS OF METALLOTHIONEIN, GLUTATHIONE-S-TRANSFERASE-PI, AND P-GLYCOPROTEIN IN CURATIVELY RESECTED GASTRIC-CANCER

Although experimental studies indicate that overexpression of metallot hionein (MT), glutathione-S-transferase-pi (GST-pi), or P-glycoprotein (P-GP) is related to the drug resistance of cancer cells, the clinica l significance of the overexpression remains to be elucidated. The exp ressions of MT, GST-pi, and P-GP were evaluated immunohistochemically in 74 specimens of gastric adenocarcinoma in T1-3N1-2 stages which wer e resected with curative intent. Fluorinated pyrimidines, mitomycin C, and Adriamycin were prescribed in 73, 54, and 2 patients, respectivel y. The staining characteristics were investigated in relation to the c linical results. The cell-proliferative activity was studied with anti -proliferating cell nuclear antigen antibody. Expressions of GST-pi an d P-GP correlated with the staining intensity of normal mucosa. Five-y ear disease-free survival rates (DFSRs) of GST-pi-negative and GST-pi- 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 a mong 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 conc urrently expressing 2 or 3 proteins have a high proliferative activity . Expressions of MT, GST-pi, and P-GP by the tumor are associated with a poorer prognosis of the patients.