Identification of Musashi-1 positive cells in normal, atypical and cancerous lesion in human gastric mucosa
Authors: Tsunehiro Takahashi, Yoshiro Saikawa, Yoshikiyo Akasaka, Tsudoi Sugiura, Kazuko Fujita, Yoshihide Otani, Tetsuro Kubota, Kouichiro Kumai, Toshiharu Ishii, Hideyuki Okano, Masaki Kitajima
Journal: Cancer Research (2004)

2788   Identification of stem cells in the stomach is still under investigation, because of the lack of useful markers for stem cell in stomach. The Musashi family is an evolutionarily conserved group of neural RNA-binding proteins in several species. The mammalian homologue; Musashi-1 (Msi-1), is known to be expressed in the crypt base columnar cells of mouse small intestine as well as in the nervous system, and Msi-1 is suggested to be a selective marker for stem cells in mouse small intestine. We hypothesized that stem cells are to exist in human stomach and originate the differentiated epithelial cells in the human gastric glands as well as in mouse small intestine. In the present study, we investigate the expression profile of Msi-1 in normal, atypical and cancerous lesion in human stomach by immunohistochemistry, in order to identify putative stem cells in the stomach, and investigate alteration of Msi-1 expression pattern in the gastric gland through carcinogenesis. Materials and Methods: Human materials were collected from normal stomach without inflammation, atypical glands (Group III) and early gastric cancer with well or poorly differentiated adenocarcinoma. Immunohistochemistry was performed using rat anti-mouse Msi-1 antibody, mouse anti-human PCNA, Ki-67, or β-catenin antibody. In gastric mucosa, Msi-1 expression was observed predominantly in the epithelial cells of the isthmus/neck region, and the cytoplasm of the epithelial cells was strongly positive for Msi-1, while the surface epithelial cells in the upper part of the pit and the epithelial cells in the base region of the glands were completely Msi-1 negative. Msi-1 expression is low in fundic mucosa compared with in the pyloric mucosa. Expression patterns of Msi-1 in relation to proliferative activity in human stomach were examined by double-staining for Msi-1 and PCNA/Ki-67, demonstrating that Msi-1-positive cells showed no PCNA/Ki-67 expression, indicating that Msi-1-positive cells remain in a dormant state. As recent study showed elevated levels of β-catenin in epidermal stem cells, Msi-1-positive cells in the base region of the glands showed β-catenin expression. In carcinogenesis, moderately Msi-1-positive cells were scattered in atypical gastric gland without localization as seen in normal gland, and the cytoplasm was stained by Msi-1 in the Msi-positive cells of atypical gastric gland. In addition, localization of Msi-positive cells described in normal mucosa was also disappeared in early gastric cancer. Msi staining level was weakened in early well differentiated adenocarcinoma, and disappeared in early poorly differentiated adenocarcinoma. While identification of stem cells in human gastric gland was suggested, further investigation will be necessary to elucidate the relationship between carcinogenesis and disorder of stem cell regulation.