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Elevated expression of UDP‐ N ‐acetylglucosamine: αmannoside β1,6 N ‐acetylglucosaminyltransferase is an early event in hepatocarcinogenesis
Author(s) -
Ito Yasuhiro,
Miyoshi Eiji,
Sakon Masato,
Takeda Tsutomu,
Noda Katsuhisa,
Tsujimoto Masahiko,
Ito Satoru,
Honda Hideo,
Takemura Fuminori,
Wakasa Kenichi,
Monden Morito,
Matsuura Nariaki,
Taniguchi Naoyuki
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(200002)9999:9999<::aid-ijc1118>3.0.co;2-f
Subject(s) - hepatocellular carcinoma , immunohistochemistry , cirrhosis , pathology , metastasis , biology , staining , cancer research , medicine , cancer
Previous reports have suggested that changes in oligosaccharide structures, especially β1–6 branching in N ‐glycans, which are biosynthesized by UDP‐ N ‐acetylglucosamine:α mannoside β1,6 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. β1–6 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. © 2001 Wiley‐Liss, Inc.