Different expression of glucose transporters in the progression of intrahepatic cholangiocarcinoma.
Glucose transporter (GLUT)-1 is expressed in malignant tumors and correlated with poor outcome in several cancers. Biliary intraepithelial neoplasia (BilIN) is considered to be a precursor or a noninvasive lesion of invasive cholangiocarcinoma. We examined GLUT-1 and GLUT-2 expression in 149 intrahepatic cholangiocarcinomas and 39 BilINs immunohistochemically and evaluated their correlation with clinicopathological findings and patient outcome in intrahepatic cholangiocarcinoma. Furthermore, we examined the role of GLUT-1 on migration and invasion of cholangiocarcinoma cells using GLUT-1 siRNA. In intrahepatic cholangiocarcinoma, GLUT-1 expression was frequently observed near the necrotic areas, whereas GLUT-2 expression tended to be observed in adenocarcinoma of large bile ducts. Compared with the GLUT-1-negative group, the GLUT-1-positive group showed significantly larger tumor size (P = .0031), poor differentiation (P < .0001), frequent lymphatic invasion (P = .0031) and lymph node metastasis (P < .0001), and high HIF-1α expression (P = .0297). GLUT-2 expression was significantly correlated with good differentiation (P = .0015), perihilar location (P < .0001), perineural invasion (P = .0049), and lymph node metastasis (P = .0248). The patients with GLUT-1-positive tumors showed poor disease related survival (P < .0001). The numbers of migrating and invading cells were significantly decreased in GLUT-1 siRNA transfectants of cholangiocarcinoma cells. Although, GLUT-1 was expressed in all grades of BilINs, GLUT-2 was expressed only in high-grade BilINs. Our results suggest that GLUT-1 expression correlates aggressive behavior and poor prognosis, and that GLUT-1 might be a therapeutic target of cholangiocarcinoma. GLUT-2 expression may be associated with cholangiocarcinogenesis of large bile duct and is a helpful marker for detecting high-grade BilIN lesions in atypical bile ducts.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Yuichiro
Y
Kubo
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Shinichi
S
Aishima
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Yuki
Y
Tanaka
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Koji
K
Shindo
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Yusuke
Y
Mizuuchi
Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Koichiro
K
Abe
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Ken
K
Shirabe
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Yoshihiko
Y
Maehara
Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Hiroshi
H
Honda
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: oda@surgpath.med.kyushu-u.ac.jp.
Yoshinao
Y
Oda
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005260:Female; D051273:Glucose Transporter Type 2 / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms; D008297:Male; D008875:Middle Aged; D011379:Prognosis
D027342:Excitatory Amino Acid Transporter 2; D051273:Glucose Transporter Type 2
BilIN; Cholangiocarcinoma; Glucose transporter; HIF-1