title: Expression of GLUT-1 in epithelial ovarian carcinoma: correlation with tumor cell proliferation, angiogenesis, survival and ability to predict optimal cytoreduction.
abstract: OBJECTIVE
  GLUT-1 is involved at various steps in the processes of tumor progression. The objective of this study was to examine the relationship between GLUT-1 expression and tumor proliferation and angiogenesis in epithelial ovarian carcinoma.
  
  
  METHODS
  Specimens from 213 patients with epithelial ovarian carcinoma were evaluated by immunohistochemistry for GLUT-1, Ki-67, and vascular endothelial growth factor. Tumor microvessel density was assessed with CD34 immunostaining. We investigated the relationships between GLUT-1 expression and clinicopathologic characteristics, tumor angiogenesis (tumor MVD and vascular endothelial growth factor expression), and tumor proliferation (Ki-67). The effect of GLUT-1 expression on patient survival and on the volume of residual disease after cytoreduction was determined.
  
  
  RESULTS
  There was a significant positive correlation between expression of GLUT-1, Ki-67, and microvessel density. In univariate survival analysis, high GLUT-1 expression, high Ki-67 expression and high tumor microvessel density showed a significant impact on patient survival (p=0.0001). In multivariate analysis including patients with all tumor stages, after controlling for age, race, stage, grade, MVD, and the 3 markers (GLUT-1, Ki-67 and VEGF), only age (HR 1.5; 95% CI 1-2.3), stage (HR 3.6; 95% CI 1.8-7.5) and grade (HR 2.3; 95% CI 1.2-4.5) retained their significance as independent poor prognostic factors. Tumors simultaneously overexpressing GLUT-1 and Ki-67 were less likely to be optimally cytoreduced as compared to tumors overexpressing only one or neither of those two markers (OR: 3.8, p=0.01).
  
  
  CONCLUSIONS
  Expression of GLUT-1 correlates with tumor proliferation and microvessel density in epithelial ovarian carcinoma. In addition, patients with rapidly proliferating advanced stage tumors overexpressing GLUT-1 have a lesser chance for optimal cytoreduction.
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA. asemaan@med.wayne.edu
authors.forename: Assaad
authors.initials: A
authors.lastname: Semaan
authors.forename: Adnan R
authors.initials: AR
authors.lastname: Munkarah
authors.forename: Haitham
authors.initials: H
authors.lastname: Arabi
authors.forename: Sudeshna
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: Shelly
authors.initials: S
authors.lastname: Seward
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: Aamer
authors.initials: A
authors.lastname: Qazi
authors.forename: Yasser
authors.initials: Y
authors.lastname: Hussein
authors.forename: Robert T
authors.initials: RT
authors.lastname: Morris
authors.forename: Rouba
authors.initials: R
authors.lastname: Ali-Fehmi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D000077216:Carcinoma, Ovarian Epithelial; D048708:Cell Growth Processes / Q000502:physiology; D018572:Disease-Free Survival; D005260:Female; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; C495677:SLC2A1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A