title: Expression of Notch1 and Numb in small cell lung cancer.
abstract: Notch signaling in tumorigenesis functions as an oncogene or tumor suppressor according to the type of malignancy. Numb represses intracellular Notch signaling. Previous studies have demonstrated that Notch signaling suppresses the proliferation of small cell lung cancer (SCLC) cell lines. However, in SCLC, the association between Notch1 and Numb expression and clinicopathological factors or prognosis has remained unclear. In this study, we evaluated the expression of Notch1 and Numb in SCLC. We immunohistochemically assessed 125 SCLCs that were surgically resected at 16 institutions participating in either the Hokkaido Lung Cancer Clinical Study Group Trial (HOT) or the Fukushima Investigative Group for Healing Thoracic Malignancy (FIGHT) between 2003 and 2013. Correlations between Notch1 or Numb expression and various clinicopathological features were evaluated. Notch1 expression was associated with ECOG performance status. Numb expression was associated with age, sex, and pathological histology (SCLC or Combined SCLC). Analysis of cellular biological expression did not demonstrate a significant correlation between the expression of Notch1 and of Numb. Multivariate Cox regression analysis showed that high Notch1 expression was an independent favorable prognostic factor for SCLC(hazard ratio = 0.503, P = 0.023). High Notch1 expression, but not Numb expression, is associated with favorable prognosis in SCLC.
authors.affiliation: Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Kikuchi
authors.affiliation: Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Sakakibara-Konishi
authors.affiliation: Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Furuta
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokouchi
authors.affiliation: Department of Translational Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishihara
authors.affiliation: Center for Respiratory Diseases, JCHO Hokkaido Hospital, Sapporo, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yamazaki
authors.affiliation: Department of Surgery, University of Occupational and Environmental Health, Kita-kyushu, Japan.|Department of Thoracic Surgery, Kanazawa Medical University, Uchinada, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Uramoto
authors.affiliation: Department of Surgery, University of Occupational and Environmental Health, Kita-kyushu, Japan.
authors.forename: Fumihiro
authors.initials: F
authors.lastname: Tanaka
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Harada
authors.affiliation: Department of Respiratory Disease, Sapporo City General Hospital, Sapporo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Akie
authors.affiliation: Department of Respiratory Medicine, Teine Keijinkai Hospital, Sapporo, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Sugaya
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Asahikawa Medical Center, Asahikawa, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Medicine, Obihiro Kosei Hospital, Obihiro, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Takamura
authors.affiliation: Department of Medical Oncology, KKR Sapporo Medical Center, Sapporo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Center for Respiratory Diseases, JCHO Hokkaido Hospital, Sapporo, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Harada
authors.affiliation: Department of Thoracic Surgery, Fukushima Red Cross Hospital, Fukushima, Japan.|Department of Thoracic Surgery, Fukushima Medical University, Fukushima, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Higuchi
authors.affiliation: Department of Respiratory Medicine, Teine Keijinkai Hospital, Sapporo, Japan.|Department of Respiratory Medicine, Sapporo-Kosei General Hospital, Sapporo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Honjo
authors.affiliation: Respiratory Center, Asahikawa Medical University, Asahikawa, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Minami
authors.affiliation: Department of Internal Medicine, Sunagawa City Medical Center, Sunagawa, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.|Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Oizumi
authors.affiliation: Department of Thoracic Surgery, Fukushima Medical University, Fukushima, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan.|Clinical Oncology Center, Fukushima Medical University Hospital, Fukushima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Dosaka-Akita
authors.affiliation: Department of Medical Oncology, KKR Sapporo Medical Center, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Isobe
authors.affiliation: Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Munakata
authors.affiliation: Department of Thoracic Surgery, Kanazawa Medical University, Uchinada, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000601:surgery; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D008875:Middle Aged; D015999:Multivariate Analysis; D009419:Nerve Tissue Proteins / Q000032:analysis*; D011013:Pneumonectomy; D016016:Proportional Hazards Models; D051881:Receptor, Notch1 / Q000032:analysis*; D012307:Risk Factors; D055752:Small Cell Lung Carcinoma / Q000737:chemistry* / Q000401:mortality / Q000601:surgery; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D009419:Nerve Tissue Proteins; C113026:NUMB protein, human; D051881:Receptor, Notch1
keywords: Notch1; Numb; immunohistochemistry; small cell lung cancer; surgery