Expression and localization of ATP binding cassette (ABC) family of drug transporters in gastric hepatoid adenocarcinomas.
OBJECTIVE
Hepatoid adenocarcinomas are clinically chemoresistant; however, data concerning the mechanisms of chemoresistance are lacking. ATP-binding cassette (ABC) transporters play a role in the ATP-dependent outward efflux of drugs, and their function renders tumour cells multidrug resistant. We assumed that the expression of ABC transporters may be accompanied by hepatic differentiation because most ABC transporters are dominantly expressed in hepatocytes. The aim of this study was to investigate the expression of ABC transporters in hepatoid adenocarcinomas.


RESULTS
The expression of P-glycoprotein, multidrug resistant-associated protein (MRP) 1, MRP2, MRP3 and MRP6 was investigated using immunohistochemistry in 13 cases of gastric hepatoid adenocarcinoma and 32 cases of control adenocarcinoma. P-glycoprotein was expressed in all cases examined. The positive rates of MRP1 (84.6% versus 21.9%), MRP2 (100% versus 43.8%) and MRP6 (61.5% versus 15.6%) were significantly higher in hepatoid than in control adenocarcinoma. MRP3 was negative in all hepatoid adenocarcinomas. Immunohistochemistry by polyclonal anti-carcinoembryonic antigen antibody, which detects bile canaliculi, suggested that MRP2 and MRP6 are located on bile canalicular-like structures in sheet or trabecular nests.


CONCLUSIONS
These results support the hypothesis that ABC transporters participate in the mechanisms of multidrug resistance in hepatoid adenocarcinomas.
Kamata
S
S
Department of Molecular Pathology, Chiba University Graduate School of Medicine, Chiba, Japan.
Kishimoto
T
T
Kobayashi
S
S
Miyazaki
M
M
D018528:ATP-Binding Cassette Transporters / Q000032:analysis* / Q000378:metabolism*; D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D015870:Gene Expression; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology; D026901:Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology
D018528:ATP-Binding Cassette Transporters; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human; C102029:ABCC6 protein, human; C114462:multidrug resistance-associated protein 3; C421109:multidrug resistance-associated protein 1