Ectopic expression of N-acetylglucosamine 6-O-sulfotransferase 2 in chemotherapy-resistant ovarian adenocarcinomas

Akira Kanoh, Akira Seko, Hiroko Ideo, Midori Yoshida, Mitsuharu Nomoto, Suguru Yonezawa, Masaru Sakamoto, Reiji Kannagi, Katsuko Yamashita

Mucinous and clear cell adenocarcinomas are the major histological types of ovarian epithelial cancer and are associated with a poor prognosis due to their resistance to chemotherapy. A novel tumor marker specific for ovarian mucinous and clear cell adenocarcinomas would be helpful for overcoming these serious diseases. We showed previously by enzymological characterization and RT-PCR that colonic mucinous adenocarcinoma tissues ectopically express GlcNAc6ST-2, a member of the carbohydrate 6-O-sulfotransferase family (Seko, A. et al. (2002) Glycobiology 12, 379-388). Here, we prepared a GlcNAc6ST-2-specific polyclonal antibody for immunohistochemical analysis and found that GlcNAc6ST-2 is ectopically expressed by not only colonic mucinous adenocarcinomas but also ovarian mucinous, clear cell and papillary serous adenocarcinomas. In contrast, solid serous adenocarcinomas, endometrioid adenocarcinomas, and mucinous adenomas expressed GlcNAc6ST-2 much less frequently or not at all. RT-PCR analysis confirmed that GlcNAc6ST-2 transcripts are expressed in ovarian mucinous adenocarcinomas but not in mucinous adenomas. In addition, immunohistochemical analysis using sulfated glycan-specific monoclonal antibodies showed that ovarian adenocarcinoma cells express GlcNAc 6-O-sulfated glycans, including an L-selectin ligand and its related glycans. These results indicate that GlcNAc6ST-2 would be a novel tumor antigen that is specifically expressed in ovarian mucinous, clear cell and papillary serous adenocarcinomas.