title: GLUT1 protein expression correlates with unfavourable histologic category and high risk in patients with neuroblastic tumours.
abstract: GLUT1 is a hypoxia-induced gene that has many biologically important functions, and the overexpression of the GLUT1 protein correlates with poor prognosis in several adult cancers. The clinical significance of the GLUT1 protein in peripheral neuroblastic tumours (NTs) has not been comprehensively documented. In the present retrospective study, immunohistochemical analyses revealed the presence of GLUT1 in 44/96 (46 %) NTs. Membranous GLUT1 was present in neuroblasts of 44/87 neuroblastomas (NBs) and nodular ganglioneuroblastomas (nGNBs) but was absent in ganglion cells. The presence of GLUT1 was significantly increased in NBs and nGNBs compared with maturing ganglioneuromas and intermixed ganglioneuroblastomas (P < 0.001). The proportion of NBs and nGNBs expressing GLUT1 was significantly increased in the high-risk and low/intermediate-risk groups compared with the very-low-risk group (P = 0.022) and the unfavourable compared with the favourable pathology prognostic group (P = 0.027). In the Cox regression analyses, GLUT1 expression indicated a worse overall survival (OS; hazard rate ratio (HR) 2.29, P = 0.053) and event-free survival (EFS; HR 1.68, P = 0.181) which was not attenuated by adjustment for the mitosis-karyorrhexis index and MYCN amplification (OS: adjusted HR 2.44, P = 0.053 and EFS: adjusted HR 1.63, P = 0.244). This indicated that GLUT1 protein expression was independent of mitosis-karyorrhexis index and MYCN amplification as a prognostic factor. Our data may have clinical significance because GLUT1 was also present in a higher proportion of high-risk NTs.
authors.affiliation: Department of Histopathology, Bristol Royal Infirmary, Bristol, BS2 8HW, UK. Pramila.Ramani@bristol.ac.uk
authors.forename: Pramila
authors.initials: P
authors.lastname: Ramani
authors.forename: Alison
authors.initials: A
authors.lastname: Headford
authors.forename: Margaret T
authors.initials: MT
authors.lastname: May
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics; D018305:Ganglioneuroblastoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008938:Mitosis; D000071447:N-Myc Proto-Oncogene Protein; D009336:Necrosis; D009447:Neuroblastoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics; D021141:Nucleic Acid Amplification Techniques; D015513:Oncogene Proteins / Q000235:genetics; D010524:Peripheral Nervous System Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D051272:Glucose Transporter Type 1; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; C495677:SLC2A1 protein, human