title: High expression of the putative cancer stem cell marker, DCLK1, in rectal neuroendocrine tumors.
abstract: Doublecortin-like kinase 1 (DCLK1), a microtubule-associated protein, is known to regulate neuronal differentiation, migration and neurogenesis. Recent evidence suggests that the protein is a putative marker for intestinal and pancreatic stem cells, including their cancer stem cell counterparts. The present study conducted immunohistochemical analyses for DCLK1 and the stemness marker, NANOG, in human intestinal neuroendocrine tumors (NETs), as their expression had not been previously investigated in these tumors. Eighteen patients with endoscopically resected rectal NETs were enrolled in the study. The mean age of the patients was 51 years old. The mean diameter of the resected tumors was 5.2 mm, and a histological diagnosis of NET grade G1 was formed for all tumors. Immunohistochemical analysis was performed not only for DCLK1, but also for the known NET markers, synaptophysin, chromogranin A and cluster of differentiation (CD)56. The intensity and distribution of staining were scored on a scale of 0-3 and 0-2, respectively. The sum of the scores was calculated for each specimen. Co-expression of DCLK1 and NANOG was also examined. The mean scores for DCLK1 and synaptophysin were significantly higher than those for chromogranin A (P<0.0001) and CD56 (P<0.01). There were no significant differences in the scores between DCLK1 and synaptophysin or between chromogranin A and CD56. Notably, NANOG was expressed in high quantities in all the tumor tissues studied, showing clear co-expression with DCLK1. In conclusion, DCLK1 may be a novel marker for rectal NET, potentially indicating the presence of the stemness gene product, NANOG.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan ; Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
authors.forename: Y U
authors.initials: YU
authors.lastname: Ikezono
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan ; Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Koga
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan ; Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Akiba
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan ; Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kawahara
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan ; Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan ; Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan ; Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Iwamoto
authors.affiliation: Department of Pathology, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Yano
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan ; Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kage
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Tsuruta
authors.affiliation: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan ; Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Torimura
keywords: NANOG; cancer stem cell; carcinoids; neuroendocrine tumor