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 metallothionein (MT), glutathione-S-transferase-pi (GST-pi), 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-pi, and P-GP wre 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-pi and P-GP correlated with the staining intensity of normal mucosa. Five-year 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 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-pi, and P-GP by the tumor are associated with a poorer prognosis of the patients.
Monden
N
N
Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Abe
S
S
Sutoh
I
I
Hishikawa
Y
Y
Kinugasa
S
S
Nagasue
N
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis*; D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D008297:Male; D008668:Metallothionein / Q000032:analysis*; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018809:Proliferating Cell Nuclear Antigen; D008668:Metallothionein; D005982:Glutathione Transferase