title: Distribution of Hypoxia-Inducible Factor-1α and Glucose Transporter-1 in Human Tongue Cancers.
abstract: OBJECTIVE
  Oral squamous cell carcinomas have the potential for rapid and unlimited growth. Therefore, hypoxic tissue areas are common in these malignant tumors and contribute to cancer progression, therapy resistance, and poor outcomes. The aim of the present study was to analyze the gene product distribution of hypoxia-inducible factor-1α (HIF-1α) and glucose transporter-1 (GLUT-1) in cases of tongue squamous cell carcinoma (TSCC) and to identify a preliminary correlation between these proteins and clinical staging and Brynes's histologic grading system (HGS).
  
  
  METHODS
  The sample included 57 cases of TSCC. Histologic sections of 3 μm were submitted to the immunoperoxidase method and semiquantitative analysis. The association between HIF-1α and GLUT-1 expression in TSCC and the clinical stage and the HGS of Bryne (1998) was evaluated using the χ(2) test, with the significance level set at 0.05 (α = 0.05).
  
  
  RESULTS
  HIF-1α was mainly expressed in the nucleus/cytoplasm of neoplastic cells, most specimens exhibited diffuse staining in neoplastic cells (84.2%), and focal staining was only observed in perinecrotic areas (15.8%). GLUT-1 was expressed in the cytoplasm and membrane of malignant cells, and diffuse staining was observed in all cases. The intensity of HIF-1α expression correlated significantly with clinical stage (P = .011) and HGS (P = .002). A significant association was observed between the distribution of HIF-1α expression and metastasis (P = .040). Immunoexpression of GLUT-1 correlated significantly with clinical stage (P = .002) and HGS (P = .000). GLUT-1 expression in the peripheral island was predominant in most low-grade tumors (78.6%); in the high-grade cases, the expression prevailed in the location center/periphery (55.8%). Comparison of the location of the tumor island in the different histologic grades showed a statistically significant difference (P = .025).
  
  
  CONCLUSIONS
  The expression of HIF and GLUT proteins within TSCC appears to be associated with disease stage, grade, and the presence of metastases. Additional studies are needed to evaluate the diagnostic and prognostic uses of these proteins in the treatment of TSCC.
authors: Professor, State University of Paraíba, Campina Grande, Paraíba, Brazil.
authors: Marcelo Gadelha
authors: MG
authors: Vasconcelos
authors: Professor, State University of Paraíba, Campina Grande, Paraíba, Brazil.
authors: Rodrigo Gadelha
authors: RG
authors: Vasconcelos
authors: PhD Student, Postgraduate Program, Oral Pathology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil. Electronic address: denisehelen2011@hotmail.com.
authors: Denise Hélen Imaculada
authors: DH
authors: Pereira de Oliveira
authors: PhD Student, Postgraduate Program, Oral Pathology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors: Edilmar
authors: E
authors: de Moura Santos
authors: Professor, Postgraduate Program, Oral Pathology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors: Leão Pereira
authors: LP
authors: Pinto
authors: Professor, Postgraduate Program, Oral Pathology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors: Éricka Janine Dantas
authors: ÉJ
authors: da Silveira
authors: Professor, Postgraduate Program, Oral Pathology, Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil.
authors: Lélia Maria Guedes
authors: LM
authors: Queiroz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D014062:Tongue Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D051272:Glucose Transporter Type 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit