Different expression of glucose transporters in the progression of intrahepatic cholangiocarcinoma

Yuichiro Kubo, Shinichi Aishima, Yuki Tanaka, Koji Shindo, Yusuke Mizuuchi, Koichiro Abe, Ken Shirabe, Yoshihiko Maehara, Hiroshi Honda, Yoshinao Oda

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1610-1617
Number of pages8
JournalHuman Pathology
Volume45
Issue number8
DOIs
Publication statusPublished - Aug 2014

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Cholangiocarcinoma
Facilitative Glucose Transport Proteins
Bile Pigments
Bile Ducts
Neoplasms
Small Interfering RNA
Lymph Nodes
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Different expression of glucose transporters in the progression of intrahepatic cholangiocarcinoma. / Kubo, Yuichiro; Aishima, Shinichi; Tanaka, Yuki; Shindo, Koji; Mizuuchi, Yusuke; Abe, Koichiro; Shirabe, Ken; Maehara, Yoshihiko; Honda, Hiroshi; Oda, Yoshinao.

In: Human Pathology, Vol. 45, No. 8, 08.2014, p. 1610-1617.

Research output: Contribution to journalArticle

Kubo, Yuichiro ; Aishima, Shinichi ; Tanaka, Yuki ; Shindo, Koji ; Mizuuchi, Yusuke ; Abe, Koichiro ; Shirabe, Ken ; Maehara, Yoshihiko ; Honda, Hiroshi ; Oda, Yoshinao. / Different expression of glucose transporters in the progression of intrahepatic cholangiocarcinoma. In: Human Pathology. 2014 ; Vol. 45, No. 8. pp. 1610-1617.
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AU - Tanaka, Yuki

AU - Shindo, Koji

AU - Mizuuchi, Yusuke

AU - Abe, Koichiro

AU - Shirabe, Ken

AU - Maehara, Yoshihiko

AU - Honda, Hiroshi

AU - Oda, Yoshinao

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AB - 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.

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