RUNX3 expression correlates with chief cell differentiation in human gastric cancers
Naotaka Ogasawara1,2, Tetsuya Tsukamoto1, Tsutomu Mizoshita1,2, Ken-ichi Inada1,3, Hisayo Ban1, Shinya Kondo1, Shinji Takasu1, Toshikazu Ushijima4, Kosei Ito5,6, Yoshiaki Ito5,6, Masao Ichinose7, Takafumi Ogawa8, Takashi Joh2 and Masae Tatematsu1,9
1Division of Oncological Pathology, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya, Japan 2Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Science, Mizuho-cho, Mizuho-ku, Nagoya, Japan, 3Department of Pathology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan, 4Carcinogenesis Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan 5Institute of Molecular and Cell Biology, Proteos, 6Oncology Research Institute, National University of Singapore, Singapore, 7Second Department of Internal Medicine, Wakayama Medical University, Kimiidera Wakayama-city, Japan, 8Management Division, Institute of Pathology, Kyodo Byori, Otsuwa, Nishi-ku, Japan and 9Division of Cancer Genetics, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Offprint requests to: Tetsuya Tsukamoto, MD., Ph.D., Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681 Japan. e-mail: ttsukamt@aichi-cc.jp
Summary. RUNX3 is a novel tumor suppressor in gastric carcinogenesis and an important factor for differentiation of chief cells in the normal gastric fundic mucosa. In this study, we confirmed RUNX3 immunolocalization in the fundic gland (bottom part) but minimum in surface mucous cell epithelium (top part) in the isolated gland from fundic mucosa. We also analyzed RUNX3 expression by immunohistochemistry in 102 gastric cancers and made a histological assessment of the expression of differentiation markers to evaluate interrelations. Among them, 45 and 57 cases were judged to be RUNX3 positive and negative, respectively, and 33 and 69 cases were pepsinogen I positive and negative, with no link to histological types. RUNX3 expression was significantly associated with that of pepsinogen I (P<0.001), but not mucins, including MUC5AC and MUC6, or the parietal or intestinal phenotypes. In conclusion, the present study showed, for the first time to our knowledge, a relation between RUNX3 and pepsinogen I expression in human gastric cancers. RUNX3 is strongly associated with chief cell phenotypic expression in human gastric cancers, as well as in normal gastric mucosa, and could be considered to play an important role in maintaining the chief cell phenotype. Histol Histopathol 24, 31-40 (2009)
Key words: Gastric cancer, RUNX3, Pepsinogen I, Chief cell differentiation
DOI: 10.14670/HH-24.31