Immunohistochemical localization of P-glycoprotein and expression of the multidrug resistance-1 gene in human pancreatic cancer: relevance to indicator of better prognosis.
We investigated immunohistochemical localization of P-glycoprotein (P-gp) on paraffin-embedded sections from 103 cases of previously untreated pancreatic tumors and also analyzed multidrug resistance-1 (MDR1) gene expression by polymerase chain reaction after reverse transcription in 35 cases. High positive staining for P-gp was observed in 72.8% of pancreatic tumors and in 73.2% of ductal adenocarcinoma. In ductal adenocarcinoma, immunoreactivity of P-gp was inversely correlated with biological aggressiveness of tumors determined by histologic grading (P<0.01), tumor size (P < 0.01), retroperitoneal invasion (P < 0.01) and portal invasion (P < 0.05). Expression of the MDR1 gene was detected in all the pancreatic tumors examined and was significantly higher than that in normal pancreas (P < 0.05). The levels of MDR1 mRNA showed a moderate correlation with those of P-gp (r=0.62, P<0.0001). Higher expression levels of MDR1/P-gp significantly correlated with better prognosis of patients with ductal carcinoma (P < 0.05). Among patients with ductal carcinoma, the high staining group for P-gp revealed a 3.5-fold better prognosis compared with the low staining group (HR=3.47, 95% CI=1.62, 7.45; P=0.0016). In conclusion, MDR1 gene/P-gp expression in pancreatic cancer without chemotherapy inversely correlates with biological aggressiveness and is an independent indicator of favorable prognosis.
Suwa
H
H
Department of Pathology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Ohshio
G
G
Arao
S
S
Imamura
T
T
Yamaki
K
K
Manabe
T
T
Imamura
M
M
Hiai
H
H
Fukumoto
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis* / Q000235:genetics*; D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012333:RNA, Messenger