title: Neuroendocrine cell differentiation of poorly differentiated colorectal adenocarcinoma correlates with liver metastasis.
abstract: Poorly differentiated (PD) adenocarcinoma often retains the capacity for neuroendocrine (NE) cell differ-entiation; however, it is difficult to distinguish the NE cell differentiation by routine hematoxylin and eosin staining. It is important to detect the presence of NE cell differentiation in advanced colorectal carcinomas because these carcinomas have been shown to produce distant metastasis at the time of diagnosis and to have a particularly poor prognosis. In this study, the characteristics of PD adenocarcinoma with NE cell differentiation and its biological metastatic mechanisms were investigated. Forty-eight of 2204 colorectal cancer patients, diagnosed as having PD adenocarcinoma (2.2%) were enrolled in this study. Immunohistochemical analysis was performed with anti-chromogranin A anti-synaptophysin, anti-CD34, anti-D2-40, and anti-VEGF antibodies. The clinicopathological factors for PD adenocarcinoma with NE cell differentiation were compared with those for PD adenocarcinoma without NE cell differentiation. Microvessel density (MVD) was assessed using immunostained slides with anti-CD34 antibody and vascular endothelial growth factor (VEGF) expression in PD adenocarcinoma with NE cell differentiation was confirmed by in situ hybridization. By immunohistochemical staining for chromogranin A and synaptophysin, NE cell differentiation was detected in eight of 48 patients (16.7%) with PD adenocarcinoma. The frequency of liver metastasis at the time of diagnosis was significantly higher in patients having PD adenocarcinoma with NE cell differentiation (p=0.03). Moreover, MVD and VEGF expression level tended to be higher in patients having PD adenocarcinoma with NE cell differentiation (p=0.13 and 0.068, respectively). NE cell differentiation in PD adenocarcinoma may produce liver metastasis through microvessel formation in the tumor induced by VEGF. In PD colorectal adenocarcinoma, immunohistochemical analysis of NE markers is important for establishing the presence of NE cell differentiation and further study is necessary to evaluate the effectiveness of anti-angiogenic drugs to PD adenocarcinoma with NE cell differentiation.
authors.affiliation: Department of Surgery for Organ Function and Biological Regulation (Department of Surgery I), Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8603, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Shinji
authors.forename: Zenya
authors.initials: Z
authors.lastname: Naito
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ishiwata
authors.forename: Noritake
authors.initials: N
authors.lastname: Tanaka
authors.forename: Kiyonori
authors.initials: K
authors.lastname: Furukawa
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Tomoko
authors.initials: T
authors.lastname: Seya
authors.forename: Hayato
authors.initials: H
authors.lastname: Kan
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuruta
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Akihisa
authors.initials: A
authors.lastname: Matsuda
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Teranishi
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Ohaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Tajiri
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D058846:Antibodies, Monoclonal, Murine-Derived; D018952:Antigens, CD34 / Q000096:biosynthesis; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018952:Antigens, CD34; C500987:monoclonal antibody D2-40