Elevated expression of UDP-N-acetylglucosamine: αmannoside β1,6 N-acetylglucosaminyltransferase is an early event in hepatocarcinogenesis
✍ Scribed by Yasuhiro Ito; Eiji Miyoshi; Masato Sakon; Tsutomu Takeda; Katsuhisa Noda; Masahiko Tsujimoto; Satoru Ito; Hideo Honda; Fuminori Takemura; Ken-ichi Wakasa; Morito Monden; Nariaki Matsuura; Naoyuki Taniguchi
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- French
- Weight
- 292 KB
- Volume
- 91
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Previous reports have suggested that changes in oligosaccharide structures, especially 1-6 branching in N-glycans, which are biosynthesized by UDP-N-acetylglucosamine:␣ mannoside 1,6 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. 1-6 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.