Elevated expression of UDP-N-acetylglucosamine: alphamannoside beta1,6 N-acetylglucosaminyltransferase is an early event in hepatocarcinogenesis.
Previous reports have suggested that changes in oligosaccharide structures, especially beta1-6 branching in N-glycans, which are biosynthesized by UDP-N-acetylglucosamine:alpha mannoside beta1,6 N-acetylglucosaminyltransferase (GnT-V), are linked to tumor metastasis and invasion. In the present study, we investigated GnT-V expression in human hepatocellular carcinoma (HCC) tissues. High expression of GnT-V mRNA was observed in both HCC and the surrounding tissues but not in normal liver. Immunohistochemical study using a newly established monoclonal antibody against GnT-V revealed that positive staining of GnT-V was observed in 75% of HCC tissues and 60% of surrounding tissues and that liver cirrhosis showed much stronger staining of GnT-V than chronic hepatitis without liver cirrhosis (p = 0.0035). In contrast, all of 12 cases of atypical adenomatous hyperplasia diffusely expressed GnT-V. beta1-6 branching in N-glycans, products of GnT-V, was increased in HCC tissues with high expression of GnT-V, as judged by lectin blotting. Levels of GnT-V expression in HCC tissues were positively correlated with a low Ki-67 labeling index (p = 0.0009), small size (p < 0.0001), poor differentiation (p < 0.0001) and absence of portal invasion (p = 0.018). Furthermore, HCC cases with low or no expression of GnT-V were more likely to show recurrence than cases with high expression (p = 0.0373). These findings strongly suggest that GnT-V expression is concerned mainly with an early phase of hepatocarcinogenesis.
Department of Surgery, Osaka Seamen's Insurance Hospital, Osaka, Japan.
Y
Y
Ito
E
E
Miyoshi
M
M
Sakon
T
T
Takeda
K
K
Noda
M
M
Tsujimoto
S
S
Ito
H
H
Honda
F
F
Takemura
K
K
Wakasa
M
M
Monden
N
N
Matsuura
N
N
Taniguchi
D000368:Aged; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D002454:Cell Differentiation; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006505:Hepatitis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D037102:Lectins / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D037102:Lectins; D012333:RNA, Messenger; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase