title: Does expression of glucose transporter protein-1 relate to prognosis and angiogenesis in osteosarcoma?
abstract: BACKGROUND
  The survival of patients who present with nonmetastatic extremity osteosarcoma has dramatically improved, but there are some patients who do not respond to chemotherapy. The ability to identify patients with a poorer prognosis might allow us to target different therapy for these patients. Glucose transporter protein-1 (Glut-1), one of the key factors in glucose metabolism, has been reported to be an independent prognostic factor in various tumors. However, little is known about the role of the Glut-1 pathway in osteosarcoma.
  
  
  OBJECTIVE
  We asked (1) if Glut-1 expression is a prognostic marker for survival in patients with osteosarcoma, and (2) if there is a relationship between Glut-1 expression and tumor angiogenesis.
  
  
  METHODS
  Thirty-seven patients with resectable high-grade osteosarcomas treated between 1982 and 2007 were reviewed retrospectively. Patients were excluded if representative biopsy material and followup data were not available. The expression of Glut-1 and the number of CD34-positive microvessels for angiogenic activity were measured immunohistochemically. The median followup was 6 years 6 months (range, 11-211 months). Survival analyses were evaluated using the Kaplan-Meier method and the Cox proportional hazards model. The association between Glut-1 expression and microvessel density was analyzed using Student's t-test and chi-square test. For 12 (32.4%) of 37 patients with osteosarcoma, the expression of Glut-1 was positive, with four patients (10.8%) showing strong expression of Glut-1 protein.
  
  
  RESULTS
  The expression of Glut-1 correlated with a shorter disease-free survival period (relative risk, 20.13; 95% CI, 1.77-229.3; p=0.0016). The microvessel density mean value of positive Glut-1 expression (mean±SD, 26.5±19.4) was lower than that of negative expression (mean±SD, 46.4±35.3; Student's t-test, p=0.038). When more than 50 was defined as a high microvessel density, positive expression of Glut-1 was significantly associated with low microvessel density (chi-square test, p=0.049).
  
  
  CONCLUSIONS
  These findings indicate that Glut-1 is a potential predictor of survival in patients with osteosarcoma and that glucose metabolism may be negatively associated with angiogenesis. If substantiated in larger numbers of patients, these findings might stimulate the development of novel treatments for patients with a poorer prognosis.
  
  
  METHODS
  Level III, prognostic study. See the Instructions for Authors for a complete description of levels of evidence.
authors.affiliation: Department of Orthopaedic Surgery, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan, kubot@hiroshima-u.ac.jp.
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Kubo
authors.forename: Shoji
authors.initials: S
authors.lastname: Shimose
authors.forename: Jun
authors.initials: J
authors.lastname: Fujimori
authors.forename: Taisuke
authors.initials: T
authors.lastname: Furuta
authors.forename: Koji
authors.initials: K
authors.lastname: Arihiro
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ochi
mesh_terms: D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D001859:Bone Neoplasms / Q000098:blood supply* / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D051272:Glucose Transporter Type 1 / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D055806:Microvessels / Q000737:chemistry / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D012516:Osteosarcoma / Q000098:blood supply* / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D010027:Osteotomy; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human