title: Overexpression of cannabinoid receptor 1 in esophageal squamous cell carcinoma is correlated with metastasis to lymph nodes and distant organs, and poor prognosis.
abstract: In patients with esophageal squamous cell carcinoma (ESCC), the status of metastasis to lymph nodes is strongly associated with prognosis. Consequently, development of a biomarker to detect the presence of metastasis would be clinically valuable. In this study, we found that overexpression of cannabinoid receptor 1 (CB1R) was applicable as a marker for prediction of metastasis in ESCC. CB1R overexpression was detected immunohistochemically in 54 of 88 cases (61.4%). The intensity of CB1R expression was uniform in both intraepithelial and invasive regions in each case, and was significantly correlated with the status of metastasis to lymph nodes (P = 0.046) and distant organs (P = 0.047). Furthermore, multivariate analysis revealed that CB1R overexpression was independently associated with poor prognosis (P = 0.019). Biological analysis of CB1R overexpression using ESCC cell lines revealed that CB1R activation appeared to promote cell proliferation and invasion. On the basis of these findings, we propose that evaluation of CB1R expression status in biopsy specimens of ESCC using immunohistochemistry might be clinically useful for prediction of metastasis to lymph nodes and distant organs.
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University, 1-1, Idaigaoka, Hasama-machi, Yufu-city, Oita, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hijiya
authors.affiliation: Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine, Oita University, 1-1, Idaigaoka, Hasama-machi, Yufu-city, Oita, Japan.
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Shibata
authors.affiliation: Department of Diagnostic Pathology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu-city, Oita, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Daa
authors.affiliation: Department of Health Sciences, Oita University of Nursing and Health Sciences, 2944-9, Megusuno, Oita-city, Oita, Japan.
authors.forename: Ryoji
authors.initials: R
authors.lastname: Hamanaka
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University, 1-1, Idaigaoka, Hasama-machi, Yufu-city, Oita, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Uchida
authors.affiliation: Department of Biology, Faculty of Medicine, Oita University, 1-1, Idaigaoka, Hasama-machi, Yufu-city, Oita, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsuura
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University, 1-1, Idaigaoka, Hasama-machi, Yufu-city, Oita, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tsukamoto
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University, 1-1, Idaigaoka, Hasama-machi, Yufu-city, Oita, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Nakada
authors.affiliation: Department of Microbioloby, Faculty of Medicine, Oita University, 1-1, Idaigaoka, Hasama-machi, Yufu-city, Oita, Japan.
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Iha
authors.affiliation: Department of Gastroenterological and Pediatric Surgery, Faculty of Medicine, Oita University, 1-1, Idaigaoka, Hasama-machi, Yufu-city, Oita, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Inomata
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University, 1-1, Idaigaoka, Hasama-machi, Yufu-city, Oita, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Moriyama
mesh_terms: D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D043884:Receptor, Cannabinoid, CB1
keywords: cannabinoid receptor 1; esophageal squamous cell carcinoma; immunohistochemistry; lymph node metastasis; predictive marker